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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Med.</journal-id>
<journal-title>Frontiers in Medicine</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Med.</abbrev-journal-title>
<issn pub-type="epub">2296-858X</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fmed.2023.1179834</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Medicine</subject>
<subj-group>
<subject>Mini Review</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Glomerular hyperfiltration and hypertrophy: an evaluation of maximum values in pathological indicators to discriminate &#x201C;diseased&#x201D; from &#x201C;normal&#x201D;</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes"><name><surname>Kataoka</surname><given-names>Hiroshi</given-names></name><xref rid="c001" ref-type="corresp"><sup>&#x002A;</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/1835360/overview"/>
</contrib>
<contrib contrib-type="author"><name><surname>Nitta</surname><given-names>Kosaku</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Hoshino</surname><given-names>Junichi</given-names>
</name>
</contrib>
</contrib-group>
<aff><institution>Department of Nephrology, Tokyo Women&#x2019;s Medical University</institution>, <addr-line>Tokyo</addr-line>, <country>Japan</country></aff>
<author-notes>
<fn id="fn0001" fn-type="edited-by"><p>Edited by: Pedro Ventura-Aguiar, Massachusetts General Hospital and Harvard Medical School, United States</p></fn>
<fn id="fn0002" fn-type="edited-by"><p>Reviewed by: Bojan Jelakovic, University of Zagreb, Croatia</p></fn>
<corresp id="c001">&#x002A;Correspondence: Hiroshi Kataoka, <email>kataoka@twmu.ac.jp</email></corresp>
</author-notes>
<pub-date pub-type="epub">
<day>13</day>
<month>07</month>
<year>2023</year>
</pub-date>
<pub-date pub-type="collection">
<year>2023</year>
</pub-date>
<volume>10</volume>
<elocation-id>1179834</elocation-id>
<history>
<date date-type="received">
<day>05</day>
<month>03</month>
<year>2023</year>
</date>
<date date-type="accepted">
<day>05</day>
<month>06</month>
<year>2023</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x00A9; 2023 Kataoka, Nitta and Hoshino.</copyright-statement>
<copyright-year>2023</copyright-year>
<copyright-holder>Kataoka, Nitta and Hoshino</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/"><p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p>
</license>
</permissions>
<abstract>
<p>The success of sodium-glucose cotransporter 2 inhibitors and bariatric surgery in patients with chronic kidney disease has highlighted the importance of glomerular hyperfiltration and hypertrophy in the progression of kidney disease. Sustained glomerular hyperfiltration and hypertrophy can lead to glomerular injury and progressive kidney damage. This article explores the relationship between obesity and chronic kidney disease, focusing on the roles of glomerular hyperfiltration and hypertrophy as hallmarks of obesity-related kidney disease. The pathological mechanisms underlying this association include adipose tissue inflammation, dyslipidemia, insulin resistance, chronic systemic inflammation, oxidative stress, and overactivation of the sympathetic nervous system, as well as the renin-angiotensin aldosterone system. This article explains how glomerular hyperfiltration results from increased renal blood flow and intraglomerular hypertension, inducing mechanical stress on the filtration barrier and post-filtration structures. Injured glomeruli increase in size before sclerosing and collapsing. Therefore, using extreme values, such as the maximal glomerular diameter, could improve the understanding of the data distribution and allow for better kidney failure predictions. This review provides important insights into the mechanisms underlying glomerular hyperfiltration and hypertrophy and highlights the need for further research using glomerular size, including maximum glomerular profile, calculated using needle biopsy specimens.</p>
</abstract>
<kwd-group>
<kwd>chronic kidney disease</kwd>
<kwd>glomerular hyperfiltration</kwd>
<kwd>glomerular hypertrophy</kwd>
<kwd>obesity</kwd>
<kwd>sodium-glucose cotransporter 2 inhibitors</kwd>
<kwd>visceral fat</kwd>
<kwd>inflammation</kwd>
<kwd>extreme value</kwd>
</kwd-group>
<contract-sponsor id="cn1">Ministry of Health, Labor and Welfare of Japan</contract-sponsor>
<counts>
<fig-count count="2"/>
<table-count count="0"/>
<equation-count count="0"/>
<ref-count count="126"/>
<page-count count="8"/>
<word-count count="7191"/>
</counts>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Nephrology</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec id="sec1" sec-type="intro">
<label>1.</label>
<title>Introduction</title>
<p>Numerous studies have shown that obesity is a significant risk factor for chronic kidney disease (CKD) (<xref ref-type="bibr" rid="ref1 ref2 ref3 ref4">1&#x2013;4</xref>) and end-stage kidney disease (<xref ref-type="bibr" rid="ref5 ref6 ref7 ref8">5&#x2013;8</xref>). The link between obesity and CKD has been extensively studied, with evidence showing that excess weight and body fat can significantly damage the kidneys over time (<xref ref-type="bibr" rid="ref9 ref10 ref11">9&#x2013;11</xref>). The global spread of obesity has become a pandemic that cannot be ignored in the context of CKD (<xref ref-type="bibr" rid="ref12 ref13 ref14">12&#x2013;14</xref>), as obesity aggravates the prognosis of all kidney diseases, regardless of etiology (<xref ref-type="bibr" rid="ref13">13</xref>, <xref ref-type="bibr" rid="ref15">15</xref>). Furthermore, all patients with CKD have a latent obesity risk due to lifestyle disturbances; as such, CKD and obesity are becoming inseparable. Importantly, the reno-protective effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors (<xref ref-type="bibr" rid="ref16 ref17 ref18 ref19 ref20">16&#x2013;20</xref>) and bariatric surgery (<xref ref-type="bibr" rid="ref9">9</xref>, <xref ref-type="bibr" rid="ref21 ref22 ref23">21&#x2013;23</xref>) have been recently confirmed. Nephrologists are very interested in SGLT2 inhibitors, as, by improving glomerular hyperfiltration, these drugs significantly improve kidney disease prognosis (<xref ref-type="bibr" rid="ref19">19</xref>, <xref ref-type="bibr" rid="ref20">20</xref>). At present, the significance of glomerular hyperfiltration (<xref ref-type="bibr" rid="ref21">21</xref>, <xref ref-type="bibr" rid="ref24 ref25 ref26">24&#x2013;26</xref>) and its pathological glomerular hypertrophy (<xref ref-type="bibr" rid="ref21">21</xref>, <xref ref-type="bibr" rid="ref22">22</xref>, <xref ref-type="bibr" rid="ref27">27</xref>, <xref ref-type="bibr" rid="ref28">28</xref>) within kidney disease have returned to the spotlight. This mini-review focuses on glomerular hyperfiltration and hypertrophy, which are hallmarks of obesity-related kidney diseases; it also discusses the utility of the maximal glomerular diameter (MaxGD) as their clinical indicator and the purpose of glomerulometry in kidney pathology.</p>
</sec>
<sec id="sec2">
<label>2.</label>
<title>Visceral fat accumulation and CKD</title>
<p>Increased visceral fat accumulation can result in adipose tissue inflammation and adipokine dysregulation (<xref ref-type="bibr" rid="ref29 ref30 ref31 ref32 ref33">29&#x2013;33</xref>), leading to dyslipidemia, chronic systemic inflammation (<xref ref-type="bibr" rid="ref31">31</xref>, <xref ref-type="bibr" rid="ref34">34</xref>, <xref ref-type="bibr" rid="ref35">35</xref>), oxidative stress (<xref ref-type="bibr" rid="ref29">29</xref>), insulin resistance (<xref ref-type="bibr" rid="ref31">31</xref>, <xref ref-type="bibr" rid="ref36">36</xref>), stimulation of the brain melanocortin system (<xref ref-type="bibr" rid="ref34">34</xref>, <xref ref-type="bibr" rid="ref37">37</xref>), overactivation of the sympathetic nervous system (<xref ref-type="bibr" rid="ref37 ref38 ref39">37&#x2013;39</xref>), overactivation of the renin-angiotensin aldosterone system (<xref ref-type="bibr" rid="ref40 ref41 ref42 ref43 ref44">40&#x2013;44</xref>), mineralocorticoid receptor activation (<xref ref-type="bibr" rid="ref45">45</xref>), sodium retention (<xref ref-type="bibr" rid="ref46">46</xref>, <xref ref-type="bibr" rid="ref47">47</xref>), and expansion of the extracellular fluid volume (<xref ref-type="bibr" rid="ref47 ref48 ref49">47&#x2013;49</xref>). These conditions have complex interactions, ultimately leading to kidney damage by causing glomerular hyperfiltration (<xref ref-type="bibr" rid="ref50">50</xref>, <xref ref-type="bibr" rid="ref51">51</xref>) and inflammation (<xref ref-type="bibr" rid="ref52">52</xref>, <xref ref-type="bibr" rid="ref53">53</xref>), which are characteristics of obesity-related kidney disease (<xref ref-type="bibr" rid="ref15">15</xref>, <xref ref-type="bibr" rid="ref47">47</xref>, <xref ref-type="bibr" rid="ref54 ref55 ref56 ref57 ref58">54&#x2013;58</xref>).</p>
</sec>
<sec id="sec3">
<label>3.</label>
<title>Glomerular hyperfiltration and increased tubular sodium reabsorption in obesity</title>
<p>Glomerular hyperfiltration, one of the predominant pathophysiological features in obesity-related glomerulopathy (ORG) (<xref ref-type="bibr" rid="ref50">50</xref>, <xref ref-type="bibr" rid="ref51">51</xref>, <xref ref-type="bibr" rid="ref59 ref60 ref61 ref62 ref63 ref64">59&#x2013;64</xref>), is histologically characterized by glomerular hypertrophy with tubular hypertrophy (<xref ref-type="bibr" rid="ref51">51</xref>, <xref ref-type="bibr" rid="ref65">65</xref>). Generally, glomerular hyperfiltration is a result of the early changes in intrarenal hemodynamic function, including increased renal blood flow and intraglomerular hypertension (<xref ref-type="bibr" rid="ref66">66</xref>), in response to various stimuli, such as a high-protein intake (<xref ref-type="bibr" rid="ref67">67</xref>, <xref ref-type="bibr" rid="ref68">68</xref>), hyperglycemia or insulin resistance (<xref ref-type="bibr" rid="ref69">69</xref>, <xref ref-type="bibr" rid="ref70">70</xref>), and obesity or metabolic syndrome (<xref ref-type="bibr" rid="ref50">50</xref>, <xref ref-type="bibr" rid="ref71 ref72 ref73">71&#x2013;73</xref>). In obesity, renal plasma flow increases less than glomerular filtration rate (GFR) (<xref ref-type="bibr" rid="ref50">50</xref>, <xref ref-type="bibr" rid="ref62">62</xref>, <xref ref-type="bibr" rid="ref71">71</xref>), suggesting renal vasodilation mostly affects the glomerular afferent arteriole (<xref ref-type="bibr" rid="ref51">51</xref>). Specifically, glomerular hyperfiltration leads to mechanical stress at the filtration barrier (<xref ref-type="bibr" rid="ref50">50</xref>, <xref ref-type="bibr" rid="ref51">51</xref>, <xref ref-type="bibr" rid="ref62">62</xref>, <xref ref-type="bibr" rid="ref65">65</xref>, <xref ref-type="bibr" rid="ref71">71</xref>, <xref ref-type="bibr" rid="ref74">74</xref>), stretching the glomerular capillary wall and resulting in various conditions, such as podocyte loss, mesangial expansion and sclerosis, and glomerular hypertrophy. In turn, these will increase the Bowman&#x2019;s space volume, that is, a large renal corpuscle (<xref ref-type="bibr" rid="ref65">65</xref>, <xref ref-type="bibr" rid="ref74">74</xref>, <xref ref-type="bibr" rid="ref75">75</xref>). Additionally, increased proximal tubular flow due to glomerular hyperfiltration increases delivery and reabsorption of water and solutes, causing proximal tubular epithelial hypertrophy (<xref ref-type="bibr" rid="ref65">65</xref>), proximal tubular lumen enlargement (<xref ref-type="bibr" rid="ref65">65</xref>), and tubulointerstitial inflammation and fibrosis (<xref ref-type="bibr" rid="ref50">50</xref>, <xref ref-type="bibr" rid="ref51">51</xref>). The increased proximal reabsorption of solutes results in a decreased solute delivery to the macula densa, which in turn influences tubuloglomerular feedback, inducing preglomerular vasodilation and glomerular hyperfiltration similarly to a &#x2018;vicious cycle&#x2019; (<xref ref-type="bibr" rid="ref57">57</xref>, <xref ref-type="bibr" rid="ref61">61</xref>). These changes result in the initiation and progression of kidney disease. An elevated single-nephron GFR is associated with obesity, as well as larger nephrons, glomerulosclerosis, and arteriosclerosis on kidney biopsy and risk factors for CKD (<xref ref-type="bibr" rid="ref76">76</xref>).</p>
</sec>
<sec id="sec4">
<label>4.</label>
<title>Glomerular hypertrophy and histopathological features of ORG</title>
<p>In patients with obesity or metabolic syndrome, relevant renal histopathological characteristics include glomerular hypertrophy with an enlargement of Bowman&#x2019;s space, mesangial cell or matrix proliferation, podocytopathy, glomerular basement membrane thickening, focal segmental glomerulosclerosis (FSGS), global sclerosis, tubular hypertrophy, tubular atrophy, interstitial fibrosis, arterial sclerosis, arterial hyalinosis, and focal dilatation of the afferent arteriole and glomerular perihilar capillaries (<xref ref-type="bibr" rid="ref50">50</xref>, <xref ref-type="bibr" rid="ref57">57</xref>, <xref ref-type="bibr" rid="ref63">63</xref>, <xref ref-type="bibr" rid="ref77">77</xref>, <xref ref-type="bibr" rid="ref78">78</xref>). Furthermore, lipid accumulation in the glomeruli and tubule cells has been confirmed in patients with obesity (<xref ref-type="bibr" rid="ref3">3</xref>, <xref ref-type="bibr" rid="ref57">57</xref>, <xref ref-type="bibr" rid="ref79 ref80 ref81">79&#x2013;81</xref>). Among these histological parameters, the current gold standard histologic features of ORG in humans are glomerular hypertrophy, large renal corpuscles, podocyte stressor FSGS, and tubular hypertrophy, which imply glomerular hypertension and hyperfiltration (<xref ref-type="bibr" rid="ref50">50</xref>, <xref ref-type="bibr" rid="ref57">57</xref>, <xref ref-type="bibr" rid="ref80">80</xref>, <xref ref-type="bibr" rid="ref82">82</xref>, <xref ref-type="bibr" rid="ref83">83</xref>). Glomerular hypertrophy or a large renal corpuscle has been reported as a potent kidney prognostic indicator in clinical practice (<xref ref-type="bibr" rid="ref84 ref85 ref86 ref87">84&#x2013;87</xref>) and plays an important role in patients with ORG as a simple and helpful indicator that incorporates early-to-late disease stages (<xref ref-type="bibr" rid="ref57">57</xref>, <xref ref-type="bibr" rid="ref75">75</xref>, <xref ref-type="bibr" rid="ref80">80</xref>, <xref ref-type="bibr" rid="ref87">87</xref>). Conversely, while FSGS may indicate the disease severity or long-term kidney prognosis, it is a somewhat nonspecific indicator of kidney disease in relation to showing the result of kidney damage (<xref ref-type="bibr" rid="ref86">86</xref>). The challenge in tubular hypertrophy is determining which renal tubules should be measured among the myriad of renal tubules in renal biopsy tissue. Furthermore, tubular hypertrophy assessment is complicated by the fact that increased severity of coexisting interstitial fibrosis and tubular atrophy in biopsy specimens are associated with a worse kidney outcome (<xref ref-type="bibr" rid="ref88 ref89 ref90">88&#x2013;90</xref>). Primarily, glomerular hypertrophy or a large renal corpuscle (<xref ref-type="bibr" rid="ref52">52</xref>, <xref ref-type="bibr" rid="ref75">75</xref>, <xref ref-type="bibr" rid="ref84 ref85 ref86 ref87">84&#x2013;87</xref>, <xref ref-type="bibr" rid="ref91">91</xref>) represents both glomerular hyperfiltration and glomerular inflammation and is recognized as an early marker of obesity-related kidney damage (<xref ref-type="bibr" rid="ref52">52</xref>, <xref ref-type="bibr" rid="ref63">63</xref>). Considering the prophylactic significance of early indicators in patients with obesity, increased clinical use of indicators of glomerular hypertrophy or a large renal corpuscle is desired.</p>
</sec>
<sec id="sec5" sec-type="discussions">
<label>5.</label>
<title>Discussion</title>
<sec id="sec6">
<label>5.1.</label>
<title>Pathological assessment of glomerular hyperfiltration</title>
<p>Kidney biopsy can help identifying the underlying cause of kidney disease and assess disease progression and treatment effectiveness (<xref ref-type="bibr" rid="ref92 ref93 ref94">92&#x2013;94</xref>). Various histological indices can be used to evaluate glomerular hyperfiltration (<xref ref-type="bibr" rid="ref65">65</xref>, <xref ref-type="bibr" rid="ref75">75</xref>, <xref ref-type="bibr" rid="ref84 ref85 ref86">84&#x2013;86</xref>, <xref ref-type="bibr" rid="ref90">90</xref>, <xref ref-type="bibr" rid="ref95 ref96 ref97 ref98 ref99 ref100 ref101">95&#x2013;101</xref>). Especially, glomerular hypertrophy assessment is thought to be the most clinically significant (<xref ref-type="bibr" rid="ref84 ref85 ref86">84&#x2013;86</xref>, <xref ref-type="bibr" rid="ref90">90</xref>, <xref ref-type="bibr" rid="ref99">99</xref>, <xref ref-type="bibr" rid="ref100">100</xref>). First, glomerular hypertrophy is a direct response to glomerular hyperfiltration and represents the earliest histological change (<xref ref-type="bibr" rid="ref75">75</xref>, <xref ref-type="bibr" rid="ref102">102</xref>). As reported, glomerular hypertrophy and renal hypertrophy are observed soon after the onset of type 1 diabetic nephropathy (<xref ref-type="bibr" rid="ref103">103</xref>), and persistent renal hypertrophy precedes the development of microalbuminuria and GFR decrease (<xref ref-type="bibr" rid="ref102">102</xref>). Second, although albuminuria and proteinuria are the leading prognostic factors for CKD and progression to end-stage kidney disease (<xref ref-type="bibr" rid="ref104">104</xref>, <xref ref-type="bibr" rid="ref105">105</xref>), glomerular hypertrophy is associated with albuminuria/proteinuria and kidney function decline to a greater extent than other parameters (<xref ref-type="bibr" rid="ref80">80</xref>, <xref ref-type="bibr" rid="ref84">84</xref>, <xref ref-type="bibr" rid="ref86">86</xref>), making it a clinically important parameter to evaluate in patients with glomerular hyperfiltration. Therefore, glomerular hypertrophy assessment can aid in the early detection and monitoring of kidney disease, as well as in the development of targeted treatment strategies (<xref ref-type="bibr" rid="ref75">75</xref>). Furthermore, glomerular hypertrophy evaluated by glomerular diameter or glomerular area measurements is less prone to measurement variability, and can easily provide a more precise evaluation of glomerular hyperfiltration than tubular measurements, which are more prone to variation in tubular diameter and length (<xref ref-type="bibr" rid="ref75">75</xref>, <xref ref-type="bibr" rid="ref89">89</xref>).</p>
</sec>
<sec id="sec7">
<label>5.2.</label>
<title>Factors to keep in mind when evaluating glomerular hypertrophy</title>
<p>The size of the renal corpuscle, or glomerulus, is an important indicator of renal function and has been associated with the outcomes of kidney diseases in both experimental models (<xref ref-type="bibr" rid="ref102">102</xref>, <xref ref-type="bibr" rid="ref103">103</xref>, <xref ref-type="bibr" rid="ref106">106</xref>, <xref ref-type="bibr" rid="ref107">107</xref>) and humans (<xref ref-type="bibr" rid="ref84 ref85 ref86">84&#x2013;86</xref>, <xref ref-type="bibr" rid="ref108 ref109 ref110">108&#x2013;110</xref>). However, the currently used clinical practice guidelines and pathological classifications of glomerulonephritis do not adequately evaluate glomerular or renal corpuscle sizes as markers of a renal lesion (<xref ref-type="bibr" rid="ref75">75</xref>, <xref ref-type="bibr" rid="ref83">83</xref>, <xref ref-type="bibr" rid="ref111">111</xref>). When using glomerular hypertrophy as an effective clinical indicator, clinicians should distinguish between physiological and pathological glomerular hypertrophy and ensure the accuracy and consistency of measurements (<xref ref-type="bibr" rid="ref27">27</xref>, <xref ref-type="bibr" rid="ref75">75</xref>). Evaluating the glomerular size in clinical studies can be challenging (<xref ref-type="bibr" rid="ref84">84</xref>, <xref ref-type="bibr" rid="ref112">112</xref>) due to glomeruli heterogeneity in a single kidney (<xref ref-type="bibr" rid="ref113">113</xref>), presence of sclerosed and collapsing glomeruli, and use of different measurement techniques. Furthermore, the use of differing morphometric techniques (<xref ref-type="bibr" rid="ref114">114</xref>), sample sizes, and statistical processing in the evaluation of the glomerular size in previous studies may have influenced the inconsistent results in clinical research.</p>
</sec>
<sec id="sec8">
<label>5.3.</label>
<title>The definitions of &#x201C;normal&#x201D; and &#x201C;diseased&#x201D;</title>
<p>The definitions of &#x201C;normal&#x201D; and &#x201C;diseased&#x201D; play an important role in medical practice. A clinically useful diagnostic definition of &#x201C;normal&#x201D; is based on a measurement rage within which the disease is absent in diagnostic tests (<xref ref-type="bibr" rid="ref115">115</xref>). In kidney disease, differentiating between morbid and physiological enlargement of renal corpuscles is important, as morbid glomerular hypertrophy may involve irreversible structural changes that can lead to renal function decline (<xref ref-type="bibr" rid="ref27">27</xref>, <xref ref-type="bibr" rid="ref75">75</xref>). Physiological hypertrophy may occur as a normal response to aging or an increased demand, such as in during pregnancy. Conversely, pathological hypertrophy is a maladaptive response to various insults, such as hypertension, diabetes, and glomerulonephritis, and can result in irreversible structural changes in the kidney (<xref ref-type="bibr" rid="ref27">27</xref>, <xref ref-type="bibr" rid="ref75">75</xref>). In a previous study of IgA nephropathy, glomerular hypertrophy above a maximal diameter of 242&#x2009;&#x03BC;m was associated with follow-up proteinuria aggravation and an increase in serum creatinine levels. Enlargement of the renal corpuscle to more than 1.5 times its original diameter may be considered morbid, and this threshold effect in the renal corpuscle size may be an important consideration when evaluating renal function and disease progression (<xref ref-type="bibr" rid="ref84">84</xref>).</p>
</sec>
<sec id="sec9">
<label>5.4.</label>
<title>Points to note when measuring the glomerular size or renal corpuscle size</title>
<p>Importantly, the use of differing morphometric techniques (<xref ref-type="bibr" rid="ref114">114</xref>), sample sizes, and statistical analyses in the evaluation of the glomerular size in previous studies may have influenced inconsistent results in clinical research. There are two major methods used to investigate the glomerular size or renal corpuscle size in human kidneys: estimating the mean glomerular size and measuring the individual glomerular size (<xref ref-type="bibr" rid="ref75">75</xref>, <xref ref-type="bibr" rid="ref114">114</xref>). The traditional model-based method of Weibel and Gomez is widely applied to estimate the mean glomerular volume in biopsy specimens (<xref ref-type="bibr" rid="ref116">116</xref>), but it cannot quantify the heterogeneity of the glomerular volume distribution. An individual glomerular volume allows the assessment of glomerular size variability within the kidneys, and two representative methods of measuring individual glomerular volumes are the Cavalieri (<xref ref-type="bibr" rid="ref117">117</xref>) and maximal profile area (MPA) (<xref ref-type="bibr" rid="ref118">118</xref>) methods. The MPA method is more feasible and advisable in clinical settings, as it allows the examination of more glomeruli in small tissue samples (<xref ref-type="bibr" rid="ref119">119</xref>), while being less laborious (<xref ref-type="bibr" rid="ref114">114</xref>) than the Cavalieri method.</p>
</sec>
<sec id="sec10">
<label>5.5.</label>
<title>Mean or maximum value?</title>
<p>When measuring glomerular size (<xref ref-type="bibr" rid="ref75">75</xref>, <xref ref-type="bibr" rid="ref84">84</xref>), it is important to consider that the size of each glomerulus varies over time (<xref rid="fig1" ref-type="fig">Figure 1A</xref>) and that glomeruli of various sizes, including hypertrophied and collapsing glomeruli, can be found within the same kidney (<xref rid="fig1" ref-type="fig">Figure 1B</xref>). Indeed, injured glomeruli increase in size before sclerosing and collapsing (<xref ref-type="bibr" rid="ref120">120</xref>), and sclerosing and normal renal corpuscles with sized in the range of 160&#x2013;180&#x2009;&#x03BC;m coexisted in a study of IgA nephropathy (<xref ref-type="bibr" rid="ref84">84</xref>). Of note, the mean glomerular size may not accurately reflect the true distribution of glomerular sizes in a kidney and may conceal important prognostic information (<xref ref-type="bibr" rid="ref84">84</xref>). The use of extreme values (i.e., minimum and maximum values) in medical research is relatively rare, despite their applications in other fields, such as hydrology, earth sciences, environmental science, finance, insurance, and genetics, for forecasting unusual events (<xref ref-type="bibr" rid="ref121">121</xref>). However, we consider that the basal concept of the extreme value theory can be used to predict the occurrence of events, such as kidney failure, from limited samples, such as kidney biopsy specimens (<xref ref-type="bibr" rid="ref84">84</xref>, <xref ref-type="bibr" rid="ref121">121</xref>). This is because the mean and standard deviation, which are commonly used in medical research, are only appropriate for normally distributed data, which is often not the case in biological data (<xref ref-type="bibr" rid="ref122">122</xref>, <xref ref-type="bibr" rid="ref123">123</xref>). Primarily, the mean and standard deviation, which are two of the most common descriptive statistic measures for continuous data and can be calculated from as few as two data points, correctly signify only a &#x201C;normal&#x201D; or &#x201C;Gaussian&#x201D; value distribution and cannot accurately describe small samples (<xref ref-type="bibr" rid="ref122">122</xref>). The use of other statistical measures, such as the median and range or maximum values, could provide more informative insights into the distribution of data in diagnostic tests and allow for better prediction of unusual events (<xref ref-type="bibr" rid="ref102">102</xref>, <xref ref-type="bibr" rid="ref115">115</xref>, <xref ref-type="bibr" rid="ref124 ref125 ref126">124&#x2013;126</xref>) (<xref rid="fig2" ref-type="fig">Figure 2A</xref>). The most important phenomenon in kidney disease progression is the fact that injured glomeruli increase in size, represented by a rightward shift in the size distribution, before sclerosing and collapsing (<xref ref-type="bibr" rid="ref102">102</xref>, <xref ref-type="bibr" rid="ref120">120</xref>) (<xref rid="fig2" ref-type="fig">Figure 2B</xref>). We consider that the difference in magnitude of a rightward shift in the glomerular size distribution caused by nephron loss, as well as by direct glomerular damage, can help distinguish between compensatory and pathological glomerular hypertrophy (<xref ref-type="bibr" rid="ref75">75</xref>, <xref ref-type="bibr" rid="ref84">84</xref>). The maximum glomerular profile could be a direct indicator of the disease severity or progression, while being less susceptible to nephron loss (<xref ref-type="bibr" rid="ref27">27</xref>, <xref ref-type="bibr" rid="ref121">121</xref>).</p>
<fig position="float" id="fig1">
<label>Figure 1</label>
<caption>
<p><bold>(A)</bold> A schematic representation of the changes in glomerular size in kidney damage. Injured glomeruli increase in size before sclerosing and collapsing. The maximal hypertrophied glomerulus is shown in red. The course can be divided into two periods using the maximally hypertrophied glomerulus as a boundary: glomerular enlargement and glomerular sclerosing and collapsing. <bold>(B)</bold> Glomeruli of various sizes (including hypertrophied and collapsing glomeruli) simultaneously exist in the kidney biopsy specimen.</p>
</caption>
<graphic xlink:href="fmed-10-1179834-g001.tif"/>
</fig>
<fig position="float" id="fig2">
<label>Figure 2</label>
<caption>
<p><bold>(A)</bold> Average or median values often cannot distinguish the differences in distribution curves for normal and diseased in diagnostic tests. The gray distribution curve represents the distribution of healthy participants in a diagnostic test, while the black distribution curve represents the distribution of patients in a diagnostic test. Differences between the black and gray distribution curves can be identified by extreme values, such as maximum and minimum values, rather than by the mean and median values. <bold>(B)</bold> The differences in the distribution curves of glomerular size between healthy individuals and patients with kidney damage. The gray distribution curve represents the glomerular size distribution in healthy participants without kidney damage. The black distribution curve represents glomerular size distribution in patients with kidney damage. Pathological glomeruli can be diagnosed when hypertrophy progresses beyond a certain threshold. The greater the damage to the kidney, the more the maximum glomerular profile shifts to the right in the kidney biopsy specimens. <bold>(C)</bold> Glomerular diameter or area of the maximum glomerular profile. Measurement of the MaxGD is indicated by the yellow line and MaxGA is represented by the red line. The MaxGD is calculated as the mean of the maximal diameter of the glomerulus and the maximal chord perpendicular to the maximal diameter of the maximally hypertrophied glomerulus in the area with the maximal profile in each specimen. The position of the geometric center of the maximal profile of the glomerulus is visually identifiable. After drawing the maximal diameter that passes through the geometric center, we draw the maximal chord perpendicular to the maximal diameter. MaxGD, maximal glomerular diameter; MaxGA, maximum glomerular area.</p>
</caption>
<graphic xlink:href="fmed-10-1179834-g002.tif"/>
</fig>
</sec>
<sec id="sec11">
<label>5.6.</label>
<title>Maximal glomerular profile in needle biopsy specimens</title>
<p>We have proposed a new method that focuses on extreme values, specifically the maximal glomerular profile, such as glomerular diameter (<xref ref-type="bibr" rid="ref75">75</xref>, <xref ref-type="bibr" rid="ref84">84</xref>) or area (<xref ref-type="bibr" rid="ref87">87</xref>), to predict the progression of CKD (<xref rid="fig2" ref-type="fig">Figure 2C</xref>). The clinical value of our pathological evaluation method, which measures only the largest glomerulus instead of the average value of all glomeruli, has been confirmed in subsequent studies. We have demonstrated poor renal prognosis in patients with IgA nephropathy only by using the maximal renal corpuscle diameter, instead of the mean renal corpuscle diameter (<xref ref-type="bibr" rid="ref84">84</xref>). Glomerular hypertrophy, as indicated by a MaxGD &#x2265;242.3&#x2009;&#x03BC;m, has been shown to be a significant predictor of poor renal prognosis in patients with IgA nephropathy (<xref ref-type="bibr" rid="ref84">84</xref>). We also confirmed the MaxGD as an effective pathological factor for predicting renal IgA nephropathy prognosis in another cohort (<xref ref-type="bibr" rid="ref86">86</xref>) and in a follow-up study (<xref ref-type="bibr" rid="ref85">85</xref>). In addition, using a combination of traditional statistical methods and machine learning to identify pathophysiological factors associated with glomerular hypertrophy we demonstrated that the MaxGD is not an indicator of compensatory glomerular hypertrophy but of renal damage itself (<xref ref-type="bibr" rid="ref27">27</xref>).</p>
</sec>
</sec>
<sec id="sec12">
<label>6.</label>
<title>Perspective</title>
<p>While glomerular hyperfiltration has received more attention, there is still a lack of clinical research on its pathological index, glomerular hypertrophy. Historically, medical research assessing extreme values is not common, however, evaluating these values may help distinguish between &#x201C;normal&#x201D; and &#x201C;diseased&#x201D; states. Measurement of the MaxGD is the most clinically superior method for assessing glomerular hypertrophy in the context of glomerular hyperfiltration. This is because it provides direct information on the size of glomeruli, which can increase in response to hyperfiltration. In addition, this method is more objective, reproducible, and less influenced by interobserver variability than other methods. Overall, maximal glomerular diameter measurements offer valuable information for the pathological assessment of glomerular hyperfiltration, and can aid in the diagnosis and management of kidney diseases. Research using the maximum glomerular profile, including the MaxGD, is expected to contribute to the field of kidney disease in the future.</p>
</sec>
<sec id="sec13">
<title>Author contributions</title>
<p>HK performed the literature search and wrote the manuscript. KN and JH were involved in planning and supervising the work. All authors contributed to the article and approved the submitted version.</p>
</sec>
<sec id="sec14" sec-type="funding-information">
<title>Funding</title>
<p>This study was partly supported by a Grant-in-Aid for Intractable Renal Diseases Research and Research on Rare and Intractable Diseases, as well as by Health and Labor Sciences Research Grants from the Ministry of Health, Labor and Welfare of Japan.</p>
</sec>
<sec id="conf1" sec-type="COI-statement">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec id="sec100" sec-type="disclaimer">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
</body>
<back>
<ack>
<p>The authors appreciate the advice on the extreme value theory by Takahiro Mochizuki (deceased June 25, 2017) and his contribution to medical care and medical research in Japan.</p>
</ack>
<ref-list>
<title>References</title>
<ref id="ref1"><label>1.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>Y</given-names></name> <name><surname>Chen</surname><given-names>X</given-names></name> <name><surname>Song</surname><given-names>Y</given-names></name> <name><surname>Caballero</surname><given-names>B</given-names></name> <name><surname>Cheskin</surname><given-names>LJ</given-names></name></person-group>. <article-title>Association between obesity and kidney disease: a systematic review and meta-analysis</article-title>. <source>Kidney Int</source>. (<year>2008</year>) <volume>73</volume>:<fpage>19</fpage>&#x2013;<lpage>33</lpage>. doi: <pub-id pub-id-type="doi">10.1038/sj.ki.5002586</pub-id></citation></ref>
<ref id="ref2"><label>2.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Hsu</surname><given-names>C-y</given-names></name> <name><surname>McCulloch</surname><given-names>C</given-names></name> <name><surname>Iribarren</surname><given-names>C</given-names></name> <name><surname>Darbinian</surname><given-names>J</given-names></name> <name><surname>Go</surname><given-names>A</given-names></name></person-group>. <article-title>Body mass index and risk for end-stage renal disease</article-title>. <source>Ann Intern Med</source>. (<year>2006</year>) <volume>144</volume>:<fpage>21</fpage>&#x2013;<lpage>8</lpage>. doi: <pub-id pub-id-type="doi">10.7326/0003-4819-144-1-200601030-00006</pub-id></citation></ref>
<ref id="ref3"><label>3.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Serra</surname><given-names>A</given-names></name> <name><surname>Romero</surname><given-names>R</given-names></name> <name><surname>Lopez</surname><given-names>D</given-names></name> <name><surname>Navarro</surname><given-names>M</given-names></name> <name><surname>Esteve</surname><given-names>A</given-names></name> <name><surname>Perez</surname><given-names>N</given-names></name> <etal/></person-group>. <article-title>Renal injury in the extremely obese patients with normal renal function</article-title>. <source>Kidney Int</source>. (<year>2008</year>) <volume>73</volume>:<fpage>947</fpage>&#x2013;<lpage>55</lpage>. doi: <pub-id pub-id-type="doi">10.1038/sj.ki.5002796</pub-id>, PMID: <pub-id pub-id-type="pmid">18216780</pub-id></citation></ref>
<ref id="ref4"><label>4.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Yamagata</surname><given-names>K</given-names></name> <name><surname>Ishida</surname><given-names>K</given-names></name> <name><surname>Sairenchi</surname><given-names>T</given-names></name> <name><surname>Takahashi</surname><given-names>H</given-names></name> <name><surname>Ohba</surname><given-names>S</given-names></name> <name><surname>Shiigai</surname><given-names>T</given-names></name> <etal/></person-group>. <article-title>Risk factors for chronic kidney disease in a community-based population: a 10-year follow-up study</article-title>. <source>Kidney Int</source>. (<year>2007</year>) <volume>71</volume>:<fpage>159</fpage>&#x2013;<lpage>66</lpage>. doi: <pub-id pub-id-type="doi">10.1038/sj.ki.5002017</pub-id>, PMID: <pub-id pub-id-type="pmid">17136030</pub-id></citation></ref>
<ref id="ref5"><label>5.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Zoccali</surname><given-names>C</given-names></name></person-group>. <article-title>The obesity epidemics in ESRD: from wasting to waist?</article-title> <source>Nephrol Dial Transplant</source>. (<year>2009</year>) <volume>24</volume>:<fpage>376</fpage>&#x2013;<lpage>80</lpage>. doi: <pub-id pub-id-type="doi">10.1093/ndt/gfn589</pub-id>, PMID: <pub-id pub-id-type="pmid">18952700</pub-id></citation></ref>
<ref id="ref6"><label>6.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Iseki</surname><given-names>K</given-names></name> <name><surname>Ikemiya</surname><given-names>Y</given-names></name> <name><surname>Kinjo</surname><given-names>K</given-names></name> <name><surname>Inoue</surname><given-names>T</given-names></name> <name><surname>Iseki</surname><given-names>C</given-names></name> <name><surname>Takishita</surname><given-names>S</given-names></name></person-group>. <article-title>Body mass index and the risk of development of end-stage renal disease in a screened cohort</article-title>. <source>Kidney Int</source>. (<year>2004</year>) <volume>65</volume>:<fpage>1870</fpage>&#x2013;<lpage>6</lpage>. doi: <pub-id pub-id-type="doi">10.1111/j.1523-1755.2004.00582.x</pub-id>, PMID: <pub-id pub-id-type="pmid">15086929</pub-id></citation></ref>
<ref id="ref7"><label>7.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Vivante</surname><given-names>A</given-names></name> <name><surname>Golan</surname><given-names>E</given-names></name> <name><surname>Tzur</surname><given-names>D</given-names></name> <name><surname>Leiba</surname><given-names>A</given-names></name> <name><surname>Tirosh</surname><given-names>A</given-names></name> <name><surname>Skorecki</surname><given-names>K</given-names></name> <etal/></person-group>. <article-title>Body mass index in 1.2 million adolescents and risk for end-stage renal disease</article-title>. <source>Arch Internal Med (1960)</source>. (<year>2012</year>) <volume>172</volume>:<fpage>1644</fpage>&#x2013;<lpage>50</lpage>. doi: <pub-id pub-id-type="doi">10.1001/2013.jamainternmed.85</pub-id></citation></ref>
<ref id="ref8"><label>8.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Chang</surname><given-names>A</given-names></name> <name><surname>Grams</surname><given-names>M</given-names></name> <name><surname>Ballew</surname><given-names>S</given-names></name> <name><surname>Bilo</surname><given-names>H</given-names></name> <name><surname>Correa</surname><given-names>A</given-names></name> <name><surname>Evans</surname><given-names>M</given-names></name> <etal/></person-group>. <article-title>Adiposity and risk of decline in glomerular filtration rate: meta-analysis of individual participant data in a global consortium</article-title>. <source>BMJ Br Med J</source>. (<year>2019</year>) <volume>364</volume>:<fpage>k5301</fpage>. doi: <pub-id pub-id-type="doi">10.1136/bmj.k5301</pub-id></citation></ref>
<ref id="ref9"><label>9.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Docherty</surname><given-names>N</given-names></name> <name><surname>le Roux</surname><given-names>C</given-names></name></person-group>. <article-title>Bariatric surgery for the treatment of chronic kidney disease in obesity and type 2 diabetes mellitus</article-title>. <source>Nat Rev Nephrol</source>. (<year>2020</year>) <volume>16</volume>:<fpage>709</fpage>&#x2013;<lpage>20</lpage>. doi: <pub-id pub-id-type="doi">10.1038/s41581-020-0323-4</pub-id></citation></ref>
<ref id="ref10"><label>10.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Garofalo</surname><given-names>C</given-names></name> <name><surname>Borrelli</surname><given-names>S</given-names></name> <name><surname>Minutolo</surname><given-names>R</given-names></name> <name><surname>Chiodini</surname><given-names>P</given-names></name> <name><surname>De Nicola</surname><given-names>L</given-names></name> <name><surname>Conte</surname><given-names>G</given-names></name></person-group>. <article-title>A systematic review and meta-analysis suggests obesity predicts onset of chronic kidney disease in the general population</article-title>. <source>Kidney Int</source>. (<year>2017</year>) <volume>91</volume>:<fpage>1224</fpage>&#x2013;<lpage>35</lpage>. doi: <pub-id pub-id-type="doi">10.1016/j.kint.2016.12.013</pub-id>, PMID: <pub-id pub-id-type="pmid">28187985</pub-id></citation></ref>
<ref id="ref11"><label>11.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Xu</surname><given-names>H</given-names></name> <name><surname>Kuja Halkola</surname><given-names>R</given-names></name> <name><surname>Chen</surname><given-names>X</given-names></name> <name><surname>Magnusson</surname><given-names>PKE</given-names></name> <name><surname>Svensson</surname><given-names>P</given-names></name> <name><surname>Carrero</surname><given-names>J-J</given-names></name></person-group>. <article-title>Higher body mass index is associated with incident diabetes and chronic kidney disease independent of genetic confounding</article-title>. <source>Kidney Int</source>. (<year>2019</year>) <volume>95</volume>:<fpage>1225</fpage>&#x2013;<lpage>33</lpage>. doi: <pub-id pub-id-type="doi">10.1016/j.kint.2018.12.019</pub-id>, PMID: <pub-id pub-id-type="pmid">30898340</pub-id></citation></ref>
<ref id="ref12"><label>12.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Amor</surname><given-names>A</given-names></name> <name><surname>Casas</surname><given-names>A</given-names></name> <name><surname>Pan&#x00E9;</surname><given-names>A</given-names></name> <name><surname>Ruiz</surname><given-names>S</given-names></name> <name><surname>Montagud Marrahi</surname><given-names>E</given-names></name> <name><surname>Molina And&#x00FA;jar</surname><given-names>A</given-names></name> <etal/></person-group>. <article-title>Weight gain following pancreas transplantation in type 1 diabetes is associated with a worse glycemic profile: A retrospective cohort study</article-title>. <source>Diabetes Res Clin Pract</source>. (<year>2021</year>) <volume>179</volume>:<fpage>109026</fpage>.</citation></ref>
<ref id="ref13"><label>13.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Chen</surname><given-names>Y</given-names></name> <name><surname>Dabbas</surname><given-names>W</given-names></name> <name><surname>Gangemi</surname><given-names>A</given-names></name> <name><surname>Benedetti</surname><given-names>E</given-names></name> <name><surname>Lash</surname><given-names>J</given-names></name> <name><surname>Finn</surname><given-names>P</given-names></name> <etal/></person-group>. <article-title>Obesity management and chronic kidney disease</article-title>. <source>Semin Nephrol</source>. (<year>2021</year>) <volume>41</volume>:<fpage>392</fpage>&#x2013;<lpage>402</lpage>. doi: <pub-id pub-id-type="doi">10.1016/j.semnephrol.2021.06.010</pub-id></citation></ref>
<ref id="ref14"><label>14.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Berthoux</surname><given-names>F</given-names></name> <name><surname>Mariat</surname><given-names>C</given-names></name> <name><surname>Maillard</surname><given-names>N</given-names></name></person-group>. <article-title>Overweight/obesity revisited as a predictive risk factor in primary IgA nephropathy</article-title>. <source>Nephrol Dial Transplant</source>. (<year>2013</year>) <volume>28</volume>:<fpage>iv160</fpage>&#x2013;<lpage>6</lpage>. doi: <pub-id pub-id-type="doi">10.1093/ndt/gft286</pub-id>, PMID: <pub-id pub-id-type="pmid">24026246</pub-id></citation></ref>
<ref id="ref15"><label>15.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Kataoka</surname><given-names>H</given-names></name> <name><surname>Nitta</surname><given-names>K</given-names></name> <name><surname>Hoshino</surname><given-names>J</given-names></name></person-group>. <article-title>Visceral fat and attribute-based medicine in chronic kidney disease</article-title>. <source>Front Endocrinol</source>. (<year>2023</year>) <volume>14</volume>:<fpage>1097596</fpage>. doi: <pub-id pub-id-type="doi">10.3389/fendo.2023.1097596</pub-id>, PMID: <pub-id pub-id-type="pmid">36843595</pub-id></citation></ref>
<ref id="ref16"><label>16.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Thomson</surname><given-names>S</given-names></name> <name><surname>Rieg</surname><given-names>T</given-names></name> <name><surname>Miracle</surname><given-names>C</given-names></name> <name><surname>Mansoury</surname><given-names>H</given-names></name> <name><surname>Whaley</surname><given-names>J</given-names></name> <name><surname>Vallon</surname><given-names>V</given-names></name> <etal/></person-group>. <article-title>Acute and chronic effects of SGLT2 blockade on glomerular and tubular function in the early diabetic rat</article-title>. <source>AJP Regul Integr Comparat Physiol</source>. (<year>2012</year>) <volume>302</volume>:<fpage>R75</fpage>&#x2013;<lpage>83</lpage>. doi: <pub-id pub-id-type="doi">10.1152/ajpregu.00357.2011</pub-id>, PMID: <pub-id pub-id-type="pmid">21940401</pub-id></citation></ref>
<ref id="ref17"><label>17.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Wanner</surname><given-names>C</given-names></name> <name><surname>Inzucchi</surname><given-names>S</given-names></name> <name><surname>Lachin</surname><given-names>J</given-names></name> <name><surname>Fitchett</surname><given-names>D</given-names></name> <name><surname>von Eynatten</surname><given-names>M</given-names></name> <name><surname>Mattheus</surname><given-names>M</given-names></name> <etal/></person-group>. <article-title>Empagliflozin and progression of kidney disease in type 2 diabetes</article-title>. <source>N Engl J Med</source>. (<year>2016</year>) <volume>375</volume>:<fpage>323</fpage>&#x2013;<lpage>34</lpage>. doi: <pub-id pub-id-type="doi">10.1056/NEJMoa1515920</pub-id></citation></ref>
<ref id="ref18"><label>18.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Perkovic</surname><given-names>V</given-names></name> <name><surname>Jardine</surname><given-names>M</given-names></name> <name><surname>Neal</surname><given-names>B</given-names></name> <name><surname>Bompoint</surname><given-names>S</given-names></name> <name><surname>Heerspink</surname><given-names>HJL</given-names></name> <name><surname>Charytan</surname><given-names>D</given-names></name> <etal/></person-group>. <article-title>Canagliflozin and renal outcomes in type 2 diabetes and nephropathy</article-title>. <source>N Engl J Med</source>. (<year>2019</year>) <volume>380</volume>:<fpage>2295</fpage>&#x2013;<lpage>306</lpage>. doi: <pub-id pub-id-type="doi">10.1056/NEJMoa1811744</pub-id></citation></ref>
<ref id="ref19"><label>19.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Heerspink</surname><given-names>HJL</given-names></name> <name><surname>Stef&#x00E1;nsson</surname><given-names>B</given-names></name> <name><surname>Correa Rotter</surname><given-names>R</given-names></name> <name><surname>Chertow</surname><given-names>G</given-names></name> <name><surname>Greene</surname><given-names>T</given-names></name> <name><surname>Hou</surname><given-names>F-F</given-names></name> <etal/></person-group>. <article-title>Dapagliflozin in patients with chronic kidney disease</article-title>. <source>N Engl J Med</source>. (<year>2020</year>) <volume>383</volume>:<fpage>1436</fpage>&#x2013;<lpage>46</lpage>. doi: <pub-id pub-id-type="doi">10.1056/NEJMoa2024816</pub-id></citation></ref>
<ref id="ref20"><label>20.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Pasternak</surname><given-names>B</given-names></name> <name><surname>Wintzell</surname><given-names>V</given-names></name> <name><surname>Melbye</surname><given-names>M</given-names></name> <name><surname>Eliasson</surname><given-names>B</given-names></name> <name><surname>Svensson</surname><given-names>A-M</given-names></name> <name><surname>Franz&#x00E9;n</surname><given-names>S</given-names></name> <etal/></person-group>. <article-title>Use of sodium-glucose co-transporter 2 inhibitors and risk of serious renal events: scandinavian cohort study. BMJ</article-title>. <source>Br Med J</source>. (<year>2020</year>) <volume>369</volume>:<fpage>m1186</fpage>. doi: <pub-id pub-id-type="doi">10.1136/bmj.m1186</pub-id></citation></ref>
<ref id="ref21"><label>21.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Jiang</surname><given-names>H-W</given-names></name> <name><surname>Zhou</surname><given-names>Y</given-names></name> <name><surname>Zhou</surname><given-names>P-Y</given-names></name> <name><surname>Zhang</surname><given-names>T-Y</given-names></name> <name><surname>Hu</surname><given-names>J-Y</given-names></name> <name><surname>Bai</surname><given-names>X-T</given-names></name></person-group>. <article-title>Protective effects of bariatric surgery on kidney functions by inhibiting oxidative stress responses through activating PPAR&#x03B1; in rats with diabetes</article-title>. <source>Front Physiol</source>. (<year>2021</year>) <volume>12</volume>:<fpage>662666</fpage>. doi: <pub-id pub-id-type="doi">10.3389/fphys.2021.662666</pub-id>, PMID: <pub-id pub-id-type="pmid">34262471</pub-id></citation></ref>
<ref id="ref22"><label>22.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Xiong</surname><given-names>Y</given-names></name> <name><surname>Zhu</surname><given-names>W</given-names></name> <name><surname>Xu</surname><given-names>Q</given-names></name> <name><surname>Ruze</surname><given-names>R</given-names></name> <name><surname>Yan</surname><given-names>Z</given-names></name> <name><surname>Li</surname><given-names>J</given-names></name> <etal/></person-group>. <article-title>Sleeve gastrectomy attenuates diabetic nephropathy by upregulating nephrin expressions in diabetic obese rats</article-title>. <source>Obes Surg</source>. (<year>2020</year>) <volume>30</volume>:<fpage>2893</fpage>&#x2013;<lpage>904</lpage>. doi: <pub-id pub-id-type="doi">10.1007/s11695-020-04611-3</pub-id>, PMID: <pub-id pub-id-type="pmid">32399849</pub-id></citation></ref>
<ref id="ref23"><label>23.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Favre</surname><given-names>G</given-names></name> <name><surname>Anty</surname><given-names>R</given-names></name> <name><surname>Canivet</surname><given-names>C</given-names></name> <name><surname>Cl&#x00E9;ment</surname><given-names>G</given-names></name> <name><surname>Ben Amor</surname><given-names>I</given-names></name> <name><surname>Tran</surname><given-names>A</given-names></name> <etal/></person-group>. <article-title>Determinants associated with the correction of glomerular hyper-filtration one year after bariatric surgery</article-title>. <source>Surg Obes Relat Dis</source>. (<year>2017</year>) <volume>13</volume>:<fpage>1760</fpage>&#x2013;<lpage>6</lpage>. doi: <pub-id pub-id-type="doi">10.1016/j.soard.2017.07.018</pub-id>, PMID: <pub-id pub-id-type="pmid">28869167</pub-id></citation></ref>
<ref id="ref24"><label>24.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Cherney</surname><given-names>DZI</given-names></name> <name><surname>Perkins</surname><given-names>B</given-names></name> <name><surname>Soleymanlou</surname><given-names>N</given-names></name> <name><surname>Maione</surname><given-names>M</given-names></name> <name><surname>Lai</surname><given-names>V</given-names></name> <name><surname>Lee</surname><given-names>A</given-names></name> <etal/></person-group>. <article-title>Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus</article-title>. <source>Circulation</source>. (<year>2014</year>) <volume>129</volume>:<fpage>587</fpage>&#x2013;<lpage>97</lpage>. doi: <pub-id pub-id-type="doi">10.1161/CIRCULATIONAHA.113.005081</pub-id>, PMID: <pub-id pub-id-type="pmid">24334175</pub-id></citation></ref>
<ref id="ref25"><label>25.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Feng</surname><given-names>Y</given-names></name> <name><surname>Zhong</surname><given-names>C</given-names></name> <name><surname>Niu</surname><given-names>J</given-names></name> <name><surname>Zhang</surname><given-names>L</given-names></name> <name><surname>Zhao</surname><given-names>Y</given-names></name> <name><surname>Wang</surname><given-names>W</given-names></name> <etal/></person-group>. <article-title>Effects of sleeve gastrectomy on lipid and energy metabolism in ZDF rats via PI3K/AKT pathway</article-title>. <source>Am J Transl Res</source>. (<year>2018</year>) <volume>10</volume>:<fpage>3713</fpage>&#x2013;<lpage>22</lpage>. PMID: <pub-id pub-id-type="pmid">30662621</pub-id></citation></ref>
<ref id="ref26"><label>26.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Cortinovis</surname><given-names>M</given-names></name> <name><surname>Perico</surname><given-names>N</given-names></name> <name><surname>Ruggenenti</surname><given-names>P</given-names></name> <name><surname>Remuzzi</surname><given-names>A</given-names></name> <name><surname>Remuzzi</surname><given-names>G</given-names></name></person-group>. <article-title>Glomerular hyperfiltration</article-title>. <source>Nat Rev Nephrol</source>. (<year>2022</year>) <volume>18</volume>:<fpage>435</fpage>&#x2013;<lpage>51</lpage>. doi: <pub-id pub-id-type="doi">10.1038/s41581-022-00559-y</pub-id></citation></ref>
<ref id="ref27"><label>27.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Ushio</surname><given-names>Y</given-names></name> <name><surname>Kataoka</surname><given-names>H</given-names></name> <name><surname>Iwadoh</surname><given-names>K</given-names></name> <name><surname>Ohara</surname><given-names>M</given-names></name> <name><surname>Suzuki</surname><given-names>T</given-names></name> <name><surname>Hirata</surname><given-names>M</given-names></name> <etal/></person-group>. <article-title>Machine learning for morbid glomerular hypertrophy</article-title>. <source>Sci Rep</source>. (<year>2022</year>) <volume>12</volume>:<fpage>19155</fpage>. doi: <pub-id pub-id-type="doi">10.1038/s41598-022-23882-7</pub-id>, PMID: <pub-id pub-id-type="pmid">36351996</pub-id></citation></ref>
<ref id="ref28"><label>28.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Neff</surname><given-names>K</given-names></name> <name><surname>Elliott</surname><given-names>J</given-names></name> <name><surname>Corteville</surname><given-names>C</given-names></name> <name><surname>Abegg</surname><given-names>K</given-names></name> <name><surname>Boza</surname><given-names>C</given-names></name> <name><surname>Lutz</surname><given-names>T</given-names></name> <etal/></person-group>. <article-title>Effect of Roux-en-Y gastric bypass and diet-induced weight loss on diabetic kidney disease in the Zucker diabetic fatty rat</article-title>. <source>Surg Obes Relat Dis</source>. (<year>2017</year>) <volume>13</volume>:<fpage>21</fpage>&#x2013;<lpage>7</lpage>. doi: <pub-id pub-id-type="doi">10.1016/j.soard.2016.08.026</pub-id>, PMID: <pub-id pub-id-type="pmid">27665150</pub-id></citation></ref>
<ref id="ref29"><label>29.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Hosogai</surname><given-names>N</given-names></name> <name><surname>Fukuhara</surname><given-names>A</given-names></name> <name><surname>Oshima</surname><given-names>K</given-names></name> <name><surname>Miyata</surname><given-names>Y</given-names></name> <name><surname>Tanaka</surname><given-names>S</given-names></name> <name><surname>Segawa</surname><given-names>K</given-names></name> <etal/></person-group>. <article-title>Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation</article-title>. <source>Diabetes</source>. (<year>2007</year>) <volume>56</volume>:<fpage>901</fpage>&#x2013;<lpage>11</lpage>. doi: <pub-id pub-id-type="doi">10.2337/db06-0911</pub-id>, PMID: <pub-id pub-id-type="pmid">17395738</pub-id></citation></ref>
<ref id="ref30"><label>30.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Hall</surname><given-names>JE</given-names></name> <name><surname>da Silva</surname><given-names>AA</given-names></name> <name><surname>Do Carmo</surname><given-names>JM</given-names></name> <name><surname>Dubinion</surname><given-names>J</given-names></name> <name><surname>Hamza</surname><given-names>S</given-names></name> <name><surname>Munusamy</surname><given-names>S</given-names></name> <etal/></person-group>. <article-title>Obesity-induced hypertension: role of sympathetic nervous system, leptin, and melanocortins</article-title>. <source>J Biol Chem</source>. (<year>2010</year>) <volume>285</volume>:<fpage>17271</fpage>&#x2013;<lpage>6</lpage>. doi: <pub-id pub-id-type="doi">10.1074/jbc.R110.113175</pub-id>, PMID: <pub-id pub-id-type="pmid">20348094</pub-id></citation></ref>
<ref id="ref31"><label>31.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Gregor</surname><given-names>M</given-names></name> <name><surname>Hotamisligil</surname><given-names>G</given-names></name></person-group>. <article-title>Inflammatory mechanisms in obesity</article-title>. <source>Annu Rev Immunol</source>. (<year>2011</year>) <volume>29</volume>:<fpage>415</fpage>&#x2013;<lpage>45</lpage>. doi: <pub-id pub-id-type="doi">10.1146/annurev-immunol-031210-101322</pub-id></citation></ref>
<ref id="ref32"><label>32.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Ouchi</surname><given-names>N</given-names></name> <name><surname>Parker</surname><given-names>J</given-names></name> <name><surname>Lugus</surname><given-names>J</given-names></name> <name><surname>Walsh</surname><given-names>K</given-names></name></person-group>. <article-title>Adipokines in inflammation and metabolic disease</article-title>. <source>Nat Rev Immunol</source>. (<year>2011</year>) <volume>11</volume>:<fpage>85</fpage>&#x2013;<lpage>97</lpage>. doi: <pub-id pub-id-type="doi">10.1038/nri2921</pub-id>, PMID: <pub-id pub-id-type="pmid">21252989</pub-id></citation></ref>
<ref id="ref33"><label>33.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Sharma</surname><given-names>K</given-names></name> <name><surname>Ramachandrarao</surname><given-names>S</given-names></name> <name><surname>Qiu</surname><given-names>G</given-names></name> <name><surname>Usui</surname><given-names>HK</given-names></name> <name><surname>Zhu</surname><given-names>Y</given-names></name> <name><surname>Dunn</surname><given-names>SR</given-names></name> <etal/></person-group>. <article-title>Adiponectin regulates albuminuria and podocyte function in mice</article-title>. <source>J Clin Invest</source>. (<year>2008</year>) <volume>118</volume>:<fpage>1645</fpage>&#x2013;<lpage>56</lpage>. doi: <pub-id pub-id-type="doi">10.1172/jci32691</pub-id>, PMID: <pub-id pub-id-type="pmid">18431508</pub-id></citation></ref>
<ref id="ref34"><label>34.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Jais</surname><given-names>A</given-names></name> <name><surname>Br&#x00FC;ning</surname><given-names>J</given-names></name></person-group>. <article-title>Hypothalamic inflammation in obesity and metabolic disease</article-title>. <source>J Clin Investig</source>. (<year>2017</year>) <volume>127</volume>:<fpage>24</fpage>&#x2013;<lpage>32</lpage>. doi: <pub-id pub-id-type="doi">10.1172/JCI88878</pub-id>, PMID: <pub-id pub-id-type="pmid">28045396</pub-id></citation></ref>
<ref id="ref35"><label>35.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Hotamisligil</surname><given-names>G</given-names></name></person-group>. <article-title>Inflammation and metabolic disorders</article-title>. <source>Nature</source>. (<year>2006</year>) <volume>444</volume>:<fpage>860</fpage>&#x2013;<lpage>7</lpage>. doi: <pub-id pub-id-type="doi">10.1038/nature05485</pub-id></citation></ref>
<ref id="ref36"><label>36.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Spoto</surname><given-names>B</given-names></name> <name><surname>Pisano</surname><given-names>A</given-names></name> <name><surname>Zoccali</surname><given-names>C</given-names></name></person-group>. <article-title>Insulin resistance in chronic kidney disease: a systematic review</article-title>. <source>Am J Physiol Renal Physiol</source>. (<year>2016</year>) <volume>311</volume>:<fpage>F1087</fpage>&#x2013;<lpage>108</lpage>. doi: <pub-id pub-id-type="doi">10.1152/ajprenal.00340.2016</pub-id></citation></ref>
<ref id="ref37"><label>37.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Shi</surname><given-names>Z</given-names></name> <name><surname>Wong</surname><given-names>J</given-names></name> <name><surname>Brooks</surname><given-names>V</given-names></name></person-group>. <article-title>Obesity: sex and sympathetics. biology of sex</article-title>. <source>Differences</source>. (<year>2020</year>) <volume>11</volume>:<fpage>10</fpage>. doi: <pub-id pub-id-type="doi">10.1186/s13293-020-00286-8</pub-id></citation></ref>
<ref id="ref38"><label>38.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Alvarez</surname><given-names>G</given-names></name> <name><surname>Beske</surname><given-names>S</given-names></name> <name><surname>Ballard</surname><given-names>T</given-names></name> <name><surname>Davy</surname><given-names>K</given-names></name></person-group>. <article-title>Sympathetic neural activation in visceral obesity</article-title>. <source>Circulation</source>. (<year>2002</year>) <volume>106</volume>:<fpage>2533</fpage>&#x2013;<lpage>6</lpage>. doi: <pub-id pub-id-type="doi">10.1161/01.CIR.0000041244.79165.25</pub-id>, PMID: <pub-id pub-id-type="pmid">12427647</pub-id></citation></ref>
<ref id="ref39"><label>39.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Brooks</surname><given-names>V</given-names></name> <name><surname>Shi</surname><given-names>Z</given-names></name> <name><surname>Holwerda</surname><given-names>S</given-names></name> <name><surname>Fadel</surname><given-names>P</given-names></name></person-group>. <article-title>Obesity-induced increases in sympathetic nerve activity: sex matters</article-title>. <source>Auton Neurosci</source>. (<year>2015</year>) <volume>187</volume>:<fpage>18</fpage>&#x2013;<lpage>26</lpage>. doi: <pub-id pub-id-type="doi">10.1016/j.autneu.2014.11.006</pub-id>, PMID: <pub-id pub-id-type="pmid">25435000</pub-id></citation></ref>
<ref id="ref40"><label>40.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Gupte</surname><given-names>M</given-names></name> <name><surname>Thatcher</surname><given-names>S</given-names></name> <name><surname>Boustany Kari</surname><given-names>C</given-names></name> <name><surname>Shoemaker</surname><given-names>R</given-names></name> <name><surname>Yiannikouris</surname><given-names>F</given-names></name> <name><surname>Zhang</surname><given-names>X</given-names></name> <etal/></person-group>. <article-title>Angiotensin converting enzyme 2 contributes to sex differences in the development of obesity hypertension in C57BL/6 mice</article-title>. <source>Arterioscler Thromb Vasc Biol</source>. (<year>2012</year>) <volume>32</volume>:<fpage>1392</fpage>&#x2013;<lpage>9</lpage>. doi: <pub-id pub-id-type="doi">10.1161/ATVBAHA.112.248559</pub-id>, PMID: <pub-id pub-id-type="pmid">22460555</pub-id></citation></ref>
<ref id="ref41"><label>41.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Xue</surname><given-names>B</given-names></name> <name><surname>Yu</surname><given-names>Y</given-names></name> <name><surname>Zhang</surname><given-names>Z</given-names></name> <name><surname>Guo</surname><given-names>F</given-names></name> <name><surname>Beltz</surname><given-names>T</given-names></name> <name><surname>Thunhorst</surname><given-names>R</given-names></name> <etal/></person-group>. <article-title>Leptin mediates high-fat diet sensitization of angiotensin II-elicited hypertension by Upregulating the brain renin-angiotensin system and inflammation</article-title>. <source>Hypertension</source>. (<year>2016</year>) <volume>67</volume>:<fpage>970</fpage>&#x2013;<lpage>6</lpage>. doi: <pub-id pub-id-type="doi">10.1161/HYPERTENSIONAHA.115.06736</pub-id>, PMID: <pub-id pub-id-type="pmid">27021010</pub-id></citation></ref>
<ref id="ref42"><label>42.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Engeli</surname><given-names>S</given-names></name> <name><surname>B&#x00F6;hnke</surname><given-names>J</given-names></name> <name><surname>Gorzelniak</surname><given-names>K</given-names></name> <name><surname>Janke</surname><given-names>J</given-names></name> <name><surname>Schling</surname><given-names>P</given-names></name> <name><surname>Bader</surname><given-names>M</given-names></name> <etal/></person-group>. <article-title>Weight loss and the renin-angiotensin-aldosterone system</article-title>. <source>Hypertension</source>. (<year>2005</year>) <volume>45</volume>:<fpage>356</fpage>&#x2013;<lpage>62</lpage>. doi: <pub-id pub-id-type="doi">10.1161/01.HYP.0000154361.47683.d3</pub-id></citation></ref>
<ref id="ref43"><label>43.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Tuck</surname><given-names>ML</given-names></name> <name><surname>Sowers</surname><given-names>J</given-names></name> <name><surname>Dornfeld</surname><given-names>L</given-names></name> <name><surname>Kledzik</surname><given-names>G</given-names></name> <name><surname>Maxwell</surname><given-names>M</given-names></name></person-group>. <article-title>The effect of weight reduction on blood pressure, plasma renin activity, and plasma aldosterone levels in obese patients</article-title>. <source>N Engl J Med</source>. (<year>1981</year>) <volume>304</volume>:<fpage>930</fpage>&#x2013;<lpage>3</lpage>. doi: <pub-id pub-id-type="doi">10.1056/NEJM198104163041602</pub-id>, PMID: <pub-id pub-id-type="pmid">7010165</pub-id></citation></ref>
<ref id="ref44"><label>44.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Achard</surname><given-names>V</given-names></name> <name><surname>Boullu Ciocca</surname><given-names>S</given-names></name> <name><surname>Desbriere</surname><given-names>R</given-names></name> <name><surname>Nguyen</surname><given-names>G</given-names></name> <name><surname>Grino</surname><given-names>M</given-names></name></person-group>. <article-title>Renin receptor expression in human adipose tissue</article-title>. <source>AJP Regul Integr Comparat Physiol</source>. (<year>2007</year>) <volume>292</volume>:<fpage>R274</fpage>&#x2013;<lpage>82</lpage>. doi: <pub-id pub-id-type="doi">10.1152/ajpregu.00439.2005</pub-id></citation></ref>
<ref id="ref45"><label>45.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>de Paula</surname><given-names>R</given-names></name> <name><surname>da Silva</surname><given-names>A</given-names></name> <name><surname>Hall</surname><given-names>J</given-names></name></person-group>. <article-title>Aldosterone antagonism attenuates obesity-induced hypertension and glomerular hyperfiltration</article-title>. <source>Hypertension</source>. (<year>2004</year>) <volume>43</volume>:<fpage>41</fpage>&#x2013;<lpage>7</lpage>. doi: <pub-id pub-id-type="doi">10.1161/01.HYP.0000105624.68174.00</pub-id>, PMID: <pub-id pub-id-type="pmid">14638627</pub-id></citation></ref>
<ref id="ref46"><label>46.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Hall</surname><given-names>J</given-names></name></person-group>. <article-title>The kidney, hypertension, and obesity</article-title>. <source>Hypertension</source>. (<year>2003</year>) <volume>41</volume>:<fpage>625</fpage>&#x2013;<lpage>33</lpage>. doi: <pub-id pub-id-type="doi">10.1161/01.HYP.0000052314.95497.78</pub-id></citation></ref>
<ref id="ref47"><label>47.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Hall</surname><given-names>J</given-names></name> <name><surname>Do Carmo</surname><given-names>J</given-names></name> <name><surname>da Silva</surname><given-names>A</given-names></name> <name><surname>Wang</surname><given-names>Z</given-names></name></person-group>. <article-title>Obesity, kidney dysfunction and hypertension: mechanistic links</article-title>. <source>Nat Rev Nephrol</source>. (<year>2019</year>) <volume>15</volume>:<fpage>367</fpage>&#x2013;<lpage>85</lpage>. doi: <pub-id pub-id-type="doi">10.1038/s41581-019-0145-4</pub-id>, PMID: <pub-id pub-id-type="pmid">31015582</pub-id></citation></ref>
<ref id="ref48"><label>48.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Neeland</surname><given-names>I</given-names></name> <name><surname>Ross</surname><given-names>R</given-names></name> <name><surname>Despr&#x00E9;s</surname><given-names>J-P</given-names></name> <name><surname>Matsuzawa</surname><given-names>Y</given-names></name> <name><surname>Yamashita</surname><given-names>S</given-names></name> <name><surname>Shai</surname><given-names>I</given-names></name> <etal/></person-group>. <article-title>Visceral and ectopic fat, atherosclerosis, and cardiometabolic disease: a position statement</article-title>. <source>Lancet Diabetes Endocrinol</source>. (<year>2019</year>) <volume>7</volume>:<fpage>715</fpage>&#x2013;<lpage>25</lpage>. doi: <pub-id pub-id-type="doi">10.1016/S2213-8587(19)30084-1</pub-id>, PMID: <pub-id pub-id-type="pmid">31301983</pub-id></citation></ref>
<ref id="ref49"><label>49.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>da Silva</surname><given-names>A</given-names></name> <name><surname>do Carmo</surname><given-names>J</given-names></name> <name><surname>Li</surname><given-names>X</given-names></name> <name><surname>Wang</surname><given-names>Z</given-names></name> <name><surname>Mouton</surname><given-names>A</given-names></name> <name><surname>Hall</surname><given-names>J</given-names></name></person-group>. <article-title>Role of Hyperinsulinemia and insulin resistance in hypertension: metabolic syndrome revisited</article-title>. <source>Can J Cardiol</source>. (<year>2020</year>) <volume>36</volume>:<fpage>671</fpage>&#x2013;<lpage>82</lpage>. doi: <pub-id pub-id-type="doi">10.1016/j.cjca.2020.02.066</pub-id>, PMID: <pub-id pub-id-type="pmid">32389340</pub-id></citation></ref>
<ref id="ref50"><label>50.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Chagnac</surname><given-names>A</given-names></name> <name><surname>Herman</surname><given-names>M</given-names></name> <name><surname>Zingerman</surname><given-names>B</given-names></name> <name><surname>Erman</surname><given-names>A</given-names></name> <name><surname>Rozen-Zvi</surname><given-names>B</given-names></name> <name><surname>Hirsh</surname><given-names>J</given-names></name> <etal/></person-group>. <article-title>Obesity-induced glomerular hyperfiltration: its involvement in the pathogenesis of tubular sodium reabsorption</article-title>. <source>Nephrol Dial Transplant</source>. (<year>2008</year>) <volume>23</volume>:<fpage>3946</fpage>&#x2013;<lpage>52</lpage>. doi: <pub-id pub-id-type="doi">10.1093/ndt/gfn379</pub-id>, PMID: <pub-id pub-id-type="pmid">18622024</pub-id></citation></ref>
<ref id="ref51"><label>51.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Chagnac</surname><given-names>A</given-names></name> <name><surname>Zingerman</surname><given-names>B</given-names></name> <name><surname>Rozen Zvi</surname><given-names>B</given-names></name> <name><surname>Herman</surname><given-names>EM</given-names></name></person-group>. <article-title>Consequences of glomerular Hyperfiltration: the role of physical forces in the pathogenesis of chronic kidney disease in diabetes and obesity</article-title>. <source>Nephron J</source>. (<year>2019</year>) <volume>143</volume>:<fpage>38</fpage>&#x2013;<lpage>42</lpage>. doi: <pub-id pub-id-type="doi">10.1159/000499486</pub-id>, PMID: <pub-id pub-id-type="pmid">30947190</pub-id></citation></ref>
<ref id="ref52"><label>52.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Wu</surname><given-names>Y</given-names></name> <name><surname>Liu</surname><given-names>Z</given-names></name> <name><surname>Xiang</surname><given-names>Z</given-names></name> <name><surname>Zeng</surname><given-names>C</given-names></name> <name><surname>Chen</surname><given-names>Z</given-names></name> <name><surname>Ma</surname><given-names>X</given-names></name> <etal/></person-group>. <article-title>Obesity-related glomerulopathy: insights from gene expression profiles of the glomeruli derived from renal biopsy samples</article-title>. <source>Endocrinology</source>. (<year>2006</year>) <volume>147</volume>:<fpage>44</fpage>&#x2013;<lpage>50</lpage>. doi: <pub-id pub-id-type="doi">10.1210/en.2005-0641</pub-id>, PMID: <pub-id pub-id-type="pmid">16210374</pub-id></citation></ref>
<ref id="ref53"><label>53.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Liu</surname><given-names>Y</given-names></name> <name><surname>Wang</surname><given-names>L</given-names></name> <name><surname>Luo</surname><given-names>M</given-names></name> <name><surname>Chen</surname><given-names>N</given-names></name> <name><surname>Deng</surname><given-names>X</given-names></name> <name><surname>He</surname><given-names>J</given-names></name> <etal/></person-group>. <article-title>Inhibition of PAI-1 attenuates perirenal fat inflammation and the associated nephropathy in high-fat diet-induced obese mice</article-title>. <source>AJP Endocrinol. Metabolism</source>. (<year>2019</year>) <volume>316</volume>:<fpage>E260</fpage>&#x2013;<lpage>7</lpage>. doi: <pub-id pub-id-type="doi">10.1152/ajpendo.00387.2018</pub-id>, PMID: <pub-id pub-id-type="pmid">30532990</pub-id></citation></ref>
<ref id="ref54"><label>54.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Kotsis</surname><given-names>V</given-names></name> <name><surname>Martinez</surname><given-names>F</given-names></name> <name><surname>Trakatelli</surname><given-names>C</given-names></name> <name><surname>Redon</surname><given-names>J</given-names></name></person-group>. <article-title>Impact of obesity in kidney diseases</article-title>. <source>Nutrients</source>. (<year>2021</year>) <volume>13</volume>:<fpage>4482</fpage>. doi: <pub-id pub-id-type="doi">10.3390/nu13124482</pub-id>, PMID: <pub-id pub-id-type="pmid">34960033</pub-id></citation></ref>
<ref id="ref55"><label>55.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Praga</surname><given-names>M</given-names></name> <name><surname>Morales</surname><given-names>E</given-names></name></person-group>. <article-title>The fatty kidney: obesity and renal disease</article-title>. <source>Nephron</source>. (<year>2017</year>) <volume>136</volume>:<fpage>273</fpage>&#x2013;<lpage>6</lpage>. doi: <pub-id pub-id-type="doi">10.1159/000447674</pub-id></citation></ref>
<ref id="ref56"><label>56.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Mart&#x00ED;nez Montoro</surname><given-names>J</given-names></name> <name><surname>Morales</surname><given-names>E</given-names></name> <name><surname>Cornejo Pareja</surname><given-names>I</given-names></name> <name><surname>Tinahones</surname><given-names>F</given-names></name> <name><surname>Fern&#x00E1;ndez</surname><given-names>GJ</given-names></name></person-group>. <article-title>Obesity-related glomerulopathy: current approaches and future perspectives</article-title>. <source>Obes Rev</source>. (<year>2022</year>) <volume>23</volume>:<fpage>e13450</fpage>. doi: <pub-id pub-id-type="doi">10.1111/obr.13450</pub-id>, PMID: <pub-id pub-id-type="pmid">35362662</pub-id></citation></ref>
<ref id="ref57"><label>57.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>D&#x2019;Agati</surname><given-names>VD</given-names></name> <name><surname>Chagnac</surname><given-names>A</given-names></name> <name><surname>de Vries</surname><given-names>AP</given-names></name> <name><surname>Levi</surname><given-names>M</given-names></name> <name><surname>Porrini</surname><given-names>E</given-names></name> <name><surname>Herman-Edelstein</surname><given-names>M</given-names></name> <etal/></person-group>. <article-title>Obesity-related glomerulopathy: clinical and pathologic characteristics and pathogenesis</article-title>. <source>Nat Rev Nephrol</source>. (<year>2016</year>) <volume>12</volume>:<fpage>453</fpage>&#x2013;<lpage>71</lpage>. doi: <pub-id pub-id-type="doi">10.1038/nrneph.2016.75</pub-id>, PMID: <pub-id pub-id-type="pmid">27263398</pub-id></citation></ref>
<ref id="ref58"><label>58.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>M</given-names></name> <name><surname>Wang</surname><given-names>Z</given-names></name> <name><surname>Chen</surname><given-names>Y</given-names></name> <name><surname>Dong</surname><given-names>Y</given-names></name></person-group>. <article-title>Kidney damage caused by obesity and its feasible treatment drugs</article-title>. <source>Int J Mol Sci</source>. (<year>2022</year>) <volume>23</volume>:<fpage>23</fpage>. doi: <pub-id pub-id-type="doi">10.3390/ijms23020747</pub-id></citation></ref>
<ref id="ref59"><label>59.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Praga</surname><given-names>M</given-names></name> <name><surname>Borstein</surname><given-names>B</given-names></name> <name><surname>Andres</surname><given-names>A</given-names></name> <name><surname>Arenas</surname><given-names>J</given-names></name> <name><surname>Oliet</surname><given-names>A</given-names></name> <name><surname>Montoyo</surname><given-names>C</given-names></name> <etal/></person-group>. <article-title>Nephrotic proteinuria without hypoalbuminemia: clinical characteristics and response to angiotensin-converting enzyme inhibition</article-title>. <source>Am J Kidney Dis</source>. (<year>1991</year>) <volume>17</volume>:<fpage>330</fpage>&#x2013;<lpage>8</lpage>. doi: <pub-id pub-id-type="doi">10.1016/S0272-6386(12)80483-5</pub-id>, PMID: <pub-id pub-id-type="pmid">1996578</pub-id></citation></ref>
<ref id="ref60"><label>60.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Brenner</surname><given-names>BM</given-names></name> <name><surname>Lawler</surname><given-names>EV</given-names></name> <name><surname>Mackenzie</surname><given-names>HS</given-names></name></person-group>. <article-title>The hyperfiltration theory: a paradigm shift in nephrology</article-title>. <source>Kidney Int</source>. (<year>1996</year>) <volume>49</volume>:<fpage>1774</fpage>&#x2013;<lpage>7</lpage>. doi: <pub-id pub-id-type="doi">10.1038/ki.1996.265</pub-id>, PMID: <pub-id pub-id-type="pmid">8743495</pub-id></citation></ref>
<ref id="ref61"><label>61.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Vallon</surname><given-names>V</given-names></name> <name><surname>Richter</surname><given-names>K</given-names></name> <name><surname>Blantz</surname><given-names>RC</given-names></name> <name><surname>Thomson</surname><given-names>S</given-names></name> <name><surname>Osswald</surname><given-names>H</given-names></name></person-group>. <article-title>Glomerular hyperfiltration in experimental diabetes mellitus: potential role of tubular reabsorption</article-title>. <source>J Am Soc Nephrol</source>. (<year>1999</year>) <volume>10</volume>:<fpage>2569</fpage>&#x2013;<lpage>76</lpage>. doi: <pub-id pub-id-type="doi">10.1681/ASN.V10122569</pub-id></citation></ref>
<ref id="ref62"><label>62.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Chagnac</surname><given-names>A</given-names></name> <name><surname>Weinstein</surname><given-names>T</given-names></name> <name><surname>Korzets</surname><given-names>A</given-names></name> <name><surname>Ramadan</surname><given-names>E</given-names></name> <name><surname>Hirsch</surname><given-names>J</given-names></name> <name><surname>Gafter</surname><given-names>U</given-names></name></person-group>. <article-title>Glomerular hemodynamics in severe obesity</article-title>. <source>Am J Physiol Renal Physiol</source>. (<year>2000</year>) <volume>278</volume>:<fpage>F817</fpage>&#x2013;<lpage>22</lpage>. doi: <pub-id pub-id-type="doi">10.1152/ajprenal.2000.278.5.F817</pub-id></citation></ref>
<ref id="ref63"><label>63.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Henegar</surname><given-names>JR</given-names></name> <name><surname>Bigler</surname><given-names>SA</given-names></name> <name><surname>Henegar</surname><given-names>LK</given-names></name> <name><surname>Tyagi</surname><given-names>SC</given-names></name> <name><surname>Hall</surname><given-names>JE</given-names></name></person-group>. <article-title>Functional and structural changes in the kidney in the early stages of obesity</article-title>. <source>J Am Soc Nephrol</source>. (<year>2001</year>) <volume>12</volume>:<fpage>1211</fpage>&#x2013;<lpage>7</lpage>. doi: <pub-id pub-id-type="doi">10.1681/ASN.V1261211</pub-id>, PMID: <pub-id pub-id-type="pmid">11373344</pub-id></citation></ref>
<ref id="ref64"><label>64.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Yang</surname><given-names>S</given-names></name> <name><surname>Cao</surname><given-names>C</given-names></name> <name><surname>Deng</surname><given-names>T</given-names></name> <name><surname>Zhou</surname><given-names>Z</given-names></name></person-group>. <article-title>Obesity-related glomerulopathy: a latent change in obesity requiring more attention</article-title>. <source>Kidney Blood Press Res</source>. (<year>2020</year>) <volume>45</volume>:<fpage>510</fpage>&#x2013;<lpage>22</lpage>. doi: <pub-id pub-id-type="doi">10.1159/000507784</pub-id>, PMID: <pub-id pub-id-type="pmid">32498064</pub-id></citation></ref>
<ref id="ref65"><label>65.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Tobar</surname><given-names>A</given-names></name> <name><surname>Ori</surname><given-names>Y</given-names></name> <name><surname>Benchetrit</surname><given-names>S</given-names></name> <name><surname>Milo</surname><given-names>G</given-names></name> <name><surname>Herman Edelstein</surname><given-names>M</given-names></name> <name><surname>Zingerman</surname><given-names>B</given-names></name> <etal/></person-group>. <article-title>Proximal tubular hypertrophy and enlarged glomerular and proximal tubular urinary space in obese subjects with proteinuria</article-title>. <source>PLoS One</source>. (<year>2013</year>) <volume>8</volume>:<fpage>e75547</fpage>. doi: <pub-id pub-id-type="doi">10.1371/journal.pone.0075547</pub-id></citation></ref>
<ref id="ref66"><label>66.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Helal</surname><given-names>I</given-names></name> <name><surname>Fick Brosnahan</surname><given-names>G</given-names></name> <name><surname>Reed Gitomer</surname><given-names>B</given-names></name> <name><surname>Schrier</surname><given-names>R</given-names></name></person-group>. <article-title>Glomerular hyperfiltration: definitions, mechanisms and clinical implications</article-title>. <source>Nat Rev Nephrol</source>. (<year>2012</year>) <volume>8</volume>:<fpage>293</fpage>&#x2013;<lpage>300</lpage>. doi: <pub-id pub-id-type="doi">10.1038/nrneph.2012.19</pub-id>, PMID: <pub-id pub-id-type="pmid">22349487</pub-id></citation></ref>
<ref id="ref67"><label>67.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Bosch</surname><given-names>JP</given-names></name> <name><surname>Lauer</surname><given-names>A</given-names></name> <name><surname>Glabman</surname><given-names>S</given-names></name></person-group>. <article-title>Short-term protein loading in assessment of patients with renal disease</article-title>. <source>Am J Med</source>. (<year>1984</year>) <volume>77</volume>:<fpage>873</fpage>&#x2013;<lpage>9</lpage>. doi: <pub-id pub-id-type="doi">10.1016/0002-9343(84)90529-1</pub-id>, PMID: <pub-id pub-id-type="pmid">6496542</pub-id></citation></ref>
<ref id="ref68"><label>68.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Bergstr&#x00F6;m</surname><given-names>J</given-names></name> <name><surname>Ahlberg</surname><given-names>M</given-names></name> <name><surname>Alvestrand</surname><given-names>A</given-names></name></person-group>. <article-title>Influence of protein intake on renal hemodynamics and plasma hormone concentrations in normal subjects</article-title>. <source>Acta Med Scand</source>. (<year>1985</year>) <volume>217</volume>:<fpage>189</fpage>&#x2013;<lpage>96</lpage>. doi: <pub-id pub-id-type="doi">10.1111/j.0954-6820.1985.tb01655.x</pub-id>, PMID: <pub-id pub-id-type="pmid">3887848</pub-id></citation></ref>
<ref id="ref69"><label>69.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Bank</surname><given-names>N</given-names></name></person-group>. <article-title>Mechanisms of diabetic hyperfiltration</article-title>. <source>Kidney Int</source>. (<year>1991</year>) <volume>40</volume>:<fpage>792</fpage>&#x2013;<lpage>807</lpage>. doi: <pub-id pub-id-type="doi">10.1038/ki.1991.277</pub-id></citation></ref>
<ref id="ref70"><label>70.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Keller</surname><given-names>CK</given-names></name> <name><surname>Bergis</surname><given-names>KH</given-names></name> <name><surname>Fliser</surname><given-names>D</given-names></name> <name><surname>Ritz</surname><given-names>E</given-names></name></person-group>. <article-title>Renal findings in patients with short-term type 2 diabetes</article-title>. <source>J Am Soc Nephrol</source>. (<year>1996</year>) <volume>7</volume>:<fpage>2627</fpage>&#x2013;<lpage>35</lpage>. doi: <pub-id pub-id-type="doi">10.1681/ASN.V7122627</pub-id></citation></ref>
<ref id="ref71"><label>71.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Wuerzner</surname><given-names>G</given-names></name> <name><surname>Pruijm</surname><given-names>M</given-names></name> <name><surname>Maillard</surname><given-names>M</given-names></name> <name><surname>Bovet</surname><given-names>P</given-names></name> <name><surname>Renaud</surname><given-names>C</given-names></name> <name><surname>Burnier</surname><given-names>M</given-names></name> <etal/></person-group>. <article-title>Marked association between obesity and glomerular hyperfiltration: a cross-sectional study in an African population</article-title>. <source>Am J Kidney Dis</source>. (<year>2010</year>) <volume>56</volume>:<fpage>303</fpage>&#x2013;<lpage>12</lpage>. doi: <pub-id pub-id-type="doi">10.1053/j.ajkd.2010.03.017</pub-id>, PMID: <pub-id pub-id-type="pmid">20538392</pub-id></citation></ref>
<ref id="ref72"><label>72.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Bosma</surname><given-names>RJ</given-names></name> <name><surname>van der Heide</surname><given-names>JJ</given-names></name> <name><surname>Oosterop</surname><given-names>EJ</given-names></name> <name><surname>de Jong</surname><given-names>PE</given-names></name> <name><surname>Navis</surname><given-names>G</given-names></name></person-group>. <article-title>Body mass index is associated with altered renal hemodynamics in non-obese healthy subjects</article-title>. <source>Kidney Int</source>. (<year>2004</year>) <volume>65</volume>:<fpage>259</fpage>&#x2013;<lpage>65</lpage>. doi: <pub-id pub-id-type="doi">10.1111/j.1523-1755.2004.00351.x</pub-id>, PMID: <pub-id pub-id-type="pmid">14675058</pub-id></citation></ref>
<ref id="ref73"><label>73.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Tomaszewski</surname><given-names>M</given-names></name> <name><surname>Charchar</surname><given-names>FJ</given-names></name> <name><surname>Maric</surname><given-names>C</given-names></name> <name><surname>McClure</surname><given-names>J</given-names></name> <name><surname>Crawford</surname><given-names>L</given-names></name> <name><surname>Grzeszczak</surname><given-names>W</given-names></name> <etal/></person-group>. <article-title>Glomerular hyperfiltration: a new marker of metabolic risk</article-title>. <source>Kidney Int</source>. (<year>2007</year>) <volume>71</volume>:<fpage>816</fpage>&#x2013;<lpage>21</lpage>. doi: <pub-id pub-id-type="doi">10.1038/sj.ki.5002160</pub-id>, PMID: <pub-id pub-id-type="pmid">17332732</pub-id></citation></ref>
<ref id="ref74"><label>74.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Chagnac</surname><given-names>A</given-names></name> <name><surname>Weinstein</surname><given-names>T</given-names></name> <name><surname>Herman</surname><given-names>M</given-names></name> <name><surname>Hirsh</surname><given-names>J</given-names></name> <name><surname>Gafter</surname><given-names>U</given-names></name> <name><surname>Ori</surname><given-names>Y</given-names></name></person-group>. <article-title>The effects of weight loss on renal function in patients with severe obesity</article-title>. <source>J Am Soc Nephrol</source>. (<year>2003</year>) <volume>14</volume>:<fpage>1480</fpage>&#x2013;<lpage>6</lpage>. doi: <pub-id pub-id-type="doi">10.1097/01.ASN.0000068462.38661.89</pub-id></citation></ref>
<ref id="ref75"><label>75.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Kataoka</surname><given-names>H</given-names></name> <name><surname>Mochizuki</surname><given-names>T</given-names></name> <name><surname>Nitta</surname><given-names>K</given-names></name></person-group>. <article-title>Large renal corpuscle: clinical significance of evaluation of the largest renal corpuscle in kidney biopsy specimens</article-title>. <source>Contrib Nephrol</source>. (<year>2018</year>) <volume>195</volume>:<fpage>20</fpage>&#x2013;<lpage>30</lpage>. doi: <pub-id pub-id-type="doi">10.1159/000486931</pub-id>, PMID: <pub-id pub-id-type="pmid">29734147</pub-id></citation></ref>
<ref id="ref76"><label>76.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Denic</surname><given-names>A</given-names></name> <name><surname>Mathew</surname><given-names>J</given-names></name> <name><surname>Lerman</surname><given-names>L</given-names></name> <name><surname>Lieske</surname><given-names>J</given-names></name> <name><surname>Larson</surname><given-names>J</given-names></name> <name><surname>Alexander</surname><given-names>M</given-names></name> <etal/></person-group>. <article-title>Single-nephron glomerular filtration rate in healthy adults</article-title>. <source>N Engl J Med</source>. (<year>2017</year>) <volume>376</volume>:<fpage>2349</fpage>&#x2013;<lpage>57</lpage>. doi: <pub-id pub-id-type="doi">10.1056/NEJMoa1614329</pub-id>, PMID: <pub-id pub-id-type="pmid">28614683</pub-id></citation></ref>
<ref id="ref77"><label>77.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Lin</surname><given-names>L</given-names></name> <name><surname>Tan</surname><given-names>W</given-names></name> <name><surname>Pan</surname><given-names>X</given-names></name> <name><surname>Tian</surname><given-names>E</given-names></name> <name><surname>Wu</surname><given-names>Z</given-names></name> <name><surname>Yang</surname><given-names>J</given-names></name></person-group>. <article-title>Metabolic syndrome-related kidney injury: a review and update</article-title>. <source>Front Endocrinol</source>. (<year>2022</year>) <volume>13</volume>:<fpage>904001</fpage>. doi: <pub-id pub-id-type="doi">10.3389/fendo.2022.904001</pub-id></citation></ref>
<ref id="ref78"><label>78.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>D'Agati</surname><given-names>V</given-names></name></person-group>. <article-title>Pathologic classification of focal segmental glomerulosclerosis</article-title>. <source>Semin Nephrol</source>. (<year>2003</year>) <volume>23</volume>:<fpage>117</fpage>&#x2013;<lpage>34</lpage>. doi: <pub-id pub-id-type="doi">10.1053/snep.2003.50012</pub-id></citation></ref>
<ref id="ref79"><label>79.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Goumenos</surname><given-names>DS</given-names></name> <name><surname>Kawar</surname><given-names>B</given-names></name> <name><surname>El Nahas</surname><given-names>M</given-names></name> <name><surname>Conti</surname><given-names>S</given-names></name> <name><surname>Wagner</surname><given-names>B</given-names></name> <name><surname>Spyropoulos</surname><given-names>C</given-names></name> <etal/></person-group>. <article-title>Early histological changes in the kidney of people with morbid obesity</article-title>. <source>Nephrol Dial Transplant</source>. (<year>2009</year>) <volume>24</volume>:<fpage>3732</fpage>&#x2013;<lpage>8</lpage>. doi: <pub-id pub-id-type="doi">10.1093/ndt/gfp329</pub-id>, PMID: <pub-id pub-id-type="pmid">19596742</pub-id></citation></ref>
<ref id="ref80"><label>80.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Kambham</surname><given-names>N</given-names></name> <name><surname>Markowitz</surname><given-names>GS</given-names></name> <name><surname>Valeri</surname><given-names>AM</given-names></name> <name><surname>Lin</surname><given-names>J</given-names></name> <name><surname>D'Agati</surname><given-names>VD</given-names></name></person-group>. <article-title>Obesity-related glomerulopathy: an emerging epidemic</article-title>. <source>Kidney Int</source>. (<year>2001</year>) <volume>59</volume>:<fpage>1498</fpage>&#x2013;<lpage>509</lpage>. doi: <pub-id pub-id-type="doi">10.1046/j.1523-1755.2001.0590041498.x</pub-id>, PMID: <pub-id pub-id-type="pmid">11260414</pub-id></citation></ref>
<ref id="ref81"><label>81.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Kato</surname><given-names>S</given-names></name> <name><surname>Nazneen</surname><given-names>A</given-names></name> <name><surname>Nakashima</surname><given-names>Y</given-names></name> <name><surname>Razzaque</surname><given-names>MS</given-names></name> <name><surname>Nishino</surname><given-names>T</given-names></name> <name><surname>Furusu</surname><given-names>A</given-names></name> <etal/></person-group>. <article-title>Pathological influence of obesity on renal structural changes in chronic kidney disease</article-title>. <source>Clin Exp Nephrol</source>. (<year>2009</year>) <volume>13</volume>:<fpage>332</fpage>&#x2013;<lpage>40</lpage>. doi: <pub-id pub-id-type="doi">10.1007/s10157-009-0169-3</pub-id>, PMID: <pub-id pub-id-type="pmid">19533267</pub-id></citation></ref>
<ref id="ref82"><label>82.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Stasi</surname><given-names>A</given-names></name> <name><surname>Cosola</surname><given-names>C</given-names></name> <name><surname>Caggiano</surname><given-names>G</given-names></name> <name><surname>Cimmarusti</surname><given-names>M</given-names></name> <name><surname>Palieri</surname><given-names>R</given-names></name> <name><surname>Acquaviva</surname><given-names>P</given-names></name> <etal/></person-group>. <article-title>Obesity-related chronic kidney disease: principal mechanisms and new approaches in nutritional management</article-title>. <source>Front. Nutr.</source> (<year>2022</year>) <volume>9</volume>:<fpage>925619</fpage>. doi: <pub-id pub-id-type="doi">10.3389/fnut.2022.925619</pub-id></citation></ref>
<ref id="ref83"><label>83.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>D'Agati</surname><given-names>VD</given-names></name> <name><surname>Fogo</surname><given-names>AB</given-names></name> <name><surname>Bruijn</surname><given-names>JA</given-names></name> <name><surname>Jennette</surname><given-names>JC</given-names></name></person-group>. <article-title>Pathologic classification of focal segmental glomerulosclerosis: a working proposal</article-title>. <source>Am J Kidney Dis</source>. (<year>2004</year>) <volume>43</volume>:<fpage>368</fpage>&#x2013;<lpage>82</lpage>. doi: <pub-id pub-id-type="doi">10.1053/j.ajkd.2003.10.024</pub-id></citation></ref>
<ref id="ref84"><label>84.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Kataoka</surname><given-names>H</given-names></name> <name><surname>Ohara</surname><given-names>M</given-names></name> <name><surname>Honda</surname><given-names>K</given-names></name> <name><surname>Mochizuki</surname><given-names>T</given-names></name> <name><surname>Nitta</surname><given-names>K</given-names></name></person-group>. <article-title>Maximal glomerular diameter as a 10-year prognostic indicator for IgA nephropathy</article-title>. <source>Nephrol Dial Transplant</source>. (<year>2011</year>) <volume>26</volume>:<fpage>3937</fpage>&#x2013;<lpage>43</lpage>. doi: <pub-id pub-id-type="doi">10.1093/ndt/gfr139</pub-id>, PMID: <pub-id pub-id-type="pmid">21427079</pub-id></citation></ref>
<ref id="ref85"><label>85.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Kataoka</surname><given-names>H</given-names></name> <name><surname>Ohara</surname><given-names>M</given-names></name> <name><surname>Suzuki</surname><given-names>T</given-names></name> <name><surname>Inoue</surname><given-names>T</given-names></name> <name><surname>Akanuma</surname><given-names>T</given-names></name> <name><surname>Kawachi</surname><given-names>K</given-names></name> <etal/></person-group>. <article-title>Time series changes in pseudo-R2 values regarding maximum glomerular diameter and the Oxford MEST-C score in patients with IgA nephropathy: a long-term follow-up study</article-title>. <source>PLoS One</source>. (<year>2020</year>) <volume>15</volume>:<fpage>e0232885</fpage>. doi: <pub-id pub-id-type="doi">10.1371/journal.pone.0232885</pub-id>, PMID: <pub-id pub-id-type="pmid">32379841</pub-id></citation></ref>
<ref id="ref86"><label>86.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Kataoka</surname><given-names>H</given-names></name> <name><surname>Moriyama</surname><given-names>T</given-names></name> <name><surname>Manabe</surname><given-names>S</given-names></name> <name><surname>Kawachi</surname><given-names>K</given-names></name> <name><surname>Ushio</surname><given-names>Y</given-names></name> <name><surname>Watanabe</surname><given-names>S</given-names></name> <etal/></person-group>. <article-title>Maximum glomerular diameter and Oxford MEST-C score in IgA nephropathy: the significance of time-series changes in Pseudo-R(2) values in relation to renal outcomes</article-title>. <source>J Clin Med</source>. (<year>2019</year>) <volume>8</volume>:<fpage>8</fpage>. doi: <pub-id pub-id-type="doi">10.3390/jcm8122105</pub-id>, PMID: <pub-id pub-id-type="pmid">31810207</pub-id></citation></ref>
<ref id="ref87"><label>87.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Kataoka</surname><given-names>H</given-names></name> <name><surname>Ohara</surname><given-names>M</given-names></name> <name><surname>Shibui</surname><given-names>K</given-names></name> <name><surname>Sato</surname><given-names>M</given-names></name> <name><surname>Suzuki</surname><given-names>T</given-names></name> <name><surname>Amemiya</surname><given-names>N</given-names></name> <etal/></person-group>. <article-title>Overweight and obesity accelerate the progression of IgA nephropathy: prognostic utility of a combination of BMI and histopathological parameters</article-title>. <source>Clin Exp Nephrol</source>. (<year>2012</year>) <volume>16</volume>:<fpage>706</fpage>&#x2013;<lpage>12</lpage>. doi: <pub-id pub-id-type="doi">10.1007/s10157-012-0613-7</pub-id>, PMID: <pub-id pub-id-type="pmid">22350469</pub-id></citation></ref>
<ref id="ref88"><label>88.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>D'Agati</surname><given-names>VD</given-names></name> <name><surname>Kaskel</surname><given-names>FJ</given-names></name> <name><surname>Falk</surname><given-names>RJ</given-names></name></person-group>. <article-title>Focal segmental glomerulosclerosis</article-title>. <source>N Engl J Med</source>. (<year>2011</year>) <volume>365</volume>:<fpage>2398</fpage>&#x2013;<lpage>411</lpage>. doi: <pub-id pub-id-type="doi">10.1056/NEJMra1106556</pub-id></citation></ref>
<ref id="ref89"><label>89.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Denic</surname><given-names>A</given-names></name> <name><surname>Glassock</surname><given-names>RJ</given-names></name> <name><surname>Rule</surname><given-names>AD</given-names></name></person-group>. <article-title>Structural and functional changes with the aging kidney</article-title>. <source>Adv Chronic Kidney Dis</source>. (<year>2016</year>) <volume>23</volume>:<fpage>19</fpage>&#x2013;<lpage>28</lpage>. doi: <pub-id pub-id-type="doi">10.1053/j.ackd.2015.08.004</pub-id>, PMID: <pub-id pub-id-type="pmid">26709059</pub-id></citation></ref>
<ref id="ref90"><label>90.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Denic</surname><given-names>A</given-names></name> <name><surname>Elsherbiny</surname><given-names>H</given-names></name> <name><surname>Mullan</surname><given-names>A</given-names></name> <name><surname>Leibovich</surname><given-names>B</given-names></name> <name><surname>Thompson</surname><given-names>RH</given-names></name> <name><surname>Ricaurte Archila</surname><given-names>L</given-names></name> <etal/></person-group>. <article-title>Larger nephron size and Nephrosclerosis predict progressive CKD and mortality after radical nephrectomy for tumor and independent of kidney function</article-title>. <source>J Am Soc Nephrol</source>. (<year>2020</year>) <volume>31</volume>:<fpage>2642</fpage>&#x2013;<lpage>52</lpage>. doi: <pub-id pub-id-type="doi">10.1681/ASN.2020040449</pub-id>, PMID: <pub-id pub-id-type="pmid">32938650</pub-id></citation></ref>
<ref id="ref91"><label>91.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Brenner</surname><given-names>BM</given-names></name></person-group>. <article-title>Hemodynamically mediated glomerular injury and the progressive nature of kidney disease</article-title>. <source>Kidney Int</source>. (<year>1983</year>) <volume>23</volume>:<fpage>647</fpage>&#x2013;<lpage>55</lpage>. doi: <pub-id pub-id-type="doi">10.1038/ki.1983.72</pub-id></citation></ref>
<ref id="ref92"><label>92.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Hull</surname><given-names>K</given-names></name> <name><surname>Adenwalla</surname><given-names>S</given-names></name> <name><surname>Topham</surname><given-names>P</given-names></name> <name><surname>Graham</surname><given-names>BM</given-names></name></person-group>. <article-title>Indications and considerations for kidney biopsy: an overview of clinical considerations for the non-specialist</article-title>. <source>Clin Med</source>. (<year>2022</year>) <volume>22</volume>:<fpage>34</fpage>&#x2013;<lpage>40</lpage>. doi: <pub-id pub-id-type="doi">10.7861/clinmed.2021-0472</pub-id>, PMID: <pub-id pub-id-type="pmid">34921054</pub-id></citation></ref>
<ref id="ref93"><label>93.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Roberts</surname><given-names>IS</given-names></name> <name><surname>Cook</surname><given-names>HT</given-names></name> <name><surname>Troyanov</surname><given-names>S</given-names></name> <name><surname>Alpers</surname><given-names>CE</given-names></name> <name><surname>Amore</surname><given-names>A</given-names></name> <name><surname>Barratt</surname><given-names>J</given-names></name> <etal/></person-group>. <article-title>The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility</article-title>. <source>Kidney Int</source>. (<year>2009</year>) <volume>76</volume>:<fpage>546</fpage>&#x2013;<lpage>56</lpage>. doi: <pub-id pub-id-type="doi">10.1038/ki.2009.168</pub-id>, PMID: <pub-id pub-id-type="pmid">19571790</pub-id></citation></ref>
<ref id="ref94"><label>94.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Cattran</surname><given-names>DC</given-names></name> <name><surname>Coppo</surname><given-names>R</given-names></name> <name><surname>Cook</surname><given-names>HT</given-names></name> <name><surname>Feehally</surname><given-names>J</given-names></name> <name><surname>Roberts</surname><given-names>ISD</given-names></name> <name><surname>Troyanov</surname><given-names>S</given-names></name> <etal/></person-group>. <article-title>The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification</article-title>. <source>Kidney Int</source>. (<year>2009</year>) <volume>76</volume>:<fpage>534</fpage>&#x2013;<lpage>45</lpage>. doi: <pub-id pub-id-type="doi">10.1038/ki.2009.243</pub-id>, PMID: <pub-id pub-id-type="pmid">19571791</pub-id></citation></ref>
<ref id="ref95"><label>95.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Moriya</surname><given-names>T</given-names></name> <name><surname>Yamagishi</surname><given-names>T</given-names></name> <name><surname>Matsubara</surname><given-names>M</given-names></name> <name><surname>Ouchi</surname><given-names>M</given-names></name></person-group>. <article-title>Serial renal biopsies in normo-and microalbuminuric patients with type 2 diabetes demonstrate that loss of renal function is associated with a reduction in glomerular filtration surface secondary to mesangial expansion</article-title>. <source>J Diabetes Complicat</source>. (<year>2019</year>) <volume>33</volume>:<fpage>368</fpage>&#x2013;<lpage>73</lpage>. doi: <pub-id pub-id-type="doi">10.1016/j.jdiacomp.2019.02.002</pub-id>, PMID: <pub-id pub-id-type="pmid">30846231</pub-id></citation></ref>
<ref id="ref96"><label>96.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Vallon</surname><given-names>V</given-names></name> <name><surname>Thomson</surname><given-names>S</given-names></name></person-group>. <article-title>Renal function in diabetic disease models: the tubular system in the pathophysiology of the diabetic kidney</article-title>. <source>Annu Rev Physiol</source>. (<year>2012</year>) <volume>74</volume>:<fpage>351</fpage>&#x2013;<lpage>75</lpage>. doi: <pub-id pub-id-type="doi">10.1146/annurev-physiol-020911-153333</pub-id></citation></ref>
<ref id="ref97"><label>97.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Fogo</surname><given-names>AB</given-names></name></person-group>. <article-title>Glomerular hypertension, abnormal glomerular growth, and progression of renal diseases</article-title>. <source>Kidney Int Suppl</source>. (<year>2000</year>) <volume>75</volume>:<fpage>S15</fpage>&#x2013;<lpage>21</lpage>. doi: <pub-id pub-id-type="doi">10.1046/j.1523-1755.57.s75.5.x</pub-id>, PMID: <pub-id pub-id-type="pmid">10828756</pub-id></citation></ref>
<ref id="ref98"><label>98.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Young</surname><given-names>RJ</given-names></name> <name><surname>Hoy</surname><given-names>WE</given-names></name> <name><surname>Kincaid Smith</surname><given-names>P</given-names></name> <name><surname>Seymour</surname><given-names>AE</given-names></name> <name><surname>Bertram</surname><given-names>JF</given-names></name></person-group>. <article-title>Glomerular size and glomerulosclerosis in Australian aborigines</article-title>. <source>Am J Kidney Dis</source>. (<year>2000</year>) <volume>36</volume>:<fpage>481</fpage>&#x2013;<lpage>9</lpage>. doi: <pub-id pub-id-type="doi">10.1053/ajkd.2000.9788</pub-id>, PMID: <pub-id pub-id-type="pmid">10977779</pub-id></citation></ref>
<ref id="ref99"><label>99.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Hoy</surname><given-names>WE</given-names></name> <name><surname>Hughson</surname><given-names>MD</given-names></name> <name><surname>Diouf</surname><given-names>B</given-names></name> <name><surname>Zimanyi</surname><given-names>M</given-names></name> <name><surname>Samuel</surname><given-names>T</given-names></name> <name><surname>McNamara</surname><given-names>BJ</given-names></name> <etal/></person-group>. <article-title>Distribution of volumes of individual glomeruli in kidneys at autopsy: association with physical and clinical characteristics and with ethnic group</article-title>. <source>Am J Nephrol</source>. (<year>2011</year>) <volume>33</volume>:<fpage>15</fpage>&#x2013;<lpage>20</lpage>. doi: <pub-id pub-id-type="doi">10.1159/000327044</pub-id>, PMID: <pub-id pub-id-type="pmid">21659730</pub-id></citation></ref>
<ref id="ref100"><label>100.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Hoy</surname><given-names>WE</given-names></name> <name><surname>Hughson</surname><given-names>MD</given-names></name> <name><surname>Zimanyi</surname><given-names>M</given-names></name> <name><surname>Samuel</surname><given-names>T</given-names></name> <name><surname>Douglas-Denton</surname><given-names>R</given-names></name> <name><surname>Holden</surname><given-names>L</given-names></name> <etal/></person-group>. <article-title>Distribution of volumes of individual glomeruli in kidneys at autopsy: association with age, nephron number, birth weight and body mass index</article-title>. <source>Clin Nephrol</source>. (<year>2010</year>) <volume>74</volume>:<fpage>S105</fpage>&#x2013;<lpage>12</lpage>. doi: <pub-id pub-id-type="doi">10.5414/CNP74S105</pub-id></citation></ref>
<ref id="ref101"><label>101.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Hayslett</surname><given-names>JP</given-names></name> <name><surname>Kashgarian</surname><given-names>M</given-names></name> <name><surname>Epstein</surname><given-names>FH</given-names></name></person-group>. <article-title>Functional correlates of compensatory renal hypertrophy</article-title>. <source>J Clin Invest</source>. (<year>1968</year>) <volume>47</volume>:<fpage>774</fpage>&#x2013;<lpage>82</lpage>. doi: <pub-id pub-id-type="doi">10.1172/jci105772</pub-id>, PMID: <pub-id pub-id-type="pmid">5641618</pub-id></citation></ref>
<ref id="ref102"><label>102.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Toyota</surname><given-names>E</given-names></name> <name><surname>Ogasawara</surname><given-names>Y</given-names></name> <name><surname>Fujimoto</surname><given-names>K</given-names></name> <name><surname>Kajita</surname><given-names>T</given-names></name> <name><surname>Shigeto</surname><given-names>F</given-names></name> <name><surname>Asano</surname><given-names>T</given-names></name> <etal/></person-group>. <article-title>Global heterogeneity of glomerular volume distribution in early diabetic nephropathy</article-title>. <source>Kidney Int</source>. (<year>2004</year>) <volume>66</volume>:<fpage>855</fpage>&#x2013;<lpage>61</lpage>. doi: <pub-id pub-id-type="doi">10.1111/j.1523-1755.2004.00816.x</pub-id>, PMID: <pub-id pub-id-type="pmid">15253743</pub-id></citation></ref>
<ref id="ref103"><label>103.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Miller</surname><given-names>PL</given-names></name> <name><surname>Rennke</surname><given-names>HG</given-names></name> <name><surname>Meyer</surname><given-names>TW</given-names></name></person-group>. <article-title>Glomerular hypertrophy accelerates hypertensive glomerular injury in rats</article-title>. <source>Am J Phys</source>. (<year>1991</year>) <volume>261</volume>:<fpage>F459</fpage>&#x2013;<lpage>65</lpage>. doi: <pub-id pub-id-type="doi">10.1152/ajprenal.1991.261.3.F459</pub-id>, PMID: <pub-id pub-id-type="pmid">1887907</pub-id></citation></ref>
<ref id="ref104"><label>104.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Coresh</surname><given-names>J</given-names></name> <name><surname>Heerspink</surname><given-names>HJL</given-names></name> <name><surname>Sang</surname><given-names>Y</given-names></name> <name><surname>Matsushita</surname><given-names>K</given-names></name> <name><surname>Arnlov</surname><given-names>J</given-names></name> <name><surname>Astor</surname><given-names>B</given-names></name> <etal/></person-group>. <article-title>Change in albuminuria and subsequent risk of end-stage kidney disease: an individual participant-level consortium meta-analysis of observational studies</article-title>. <source>Lancet Diabetes Endocrinol.</source> (<year>2019</year>) <volume>7</volume>:<fpage>115</fpage>&#x2013;<lpage>27</lpage>. doi: <pub-id pub-id-type="doi">10.1016/S2213-8587(18)30313-9</pub-id>, PMID: <pub-id pub-id-type="pmid">30635225</pub-id></citation></ref>
<ref id="ref105"><label>105.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Kataoka</surname><given-names>H</given-names></name> <name><surname>Ono</surname><given-names>K</given-names></name> <name><surname>Mochizuki</surname><given-names>T</given-names></name> <name><surname>Hanafusa</surname><given-names>N</given-names></name> <name><surname>Imai</surname><given-names>E</given-names></name> <name><surname>Hishida</surname><given-names>A</given-names></name> <etal/></person-group>. <article-title>A body mass index-based cross-classification approach for the assessment of prognostic factors in chronic kidney disease progression</article-title>. <source>Kidney Blood Press Res</source>. (<year>2019</year>) <volume>44</volume>:<fpage>362</fpage>&#x2013;<lpage>83</lpage>. doi: <pub-id pub-id-type="doi">10.1159/000501021</pub-id>, PMID: <pub-id pub-id-type="pmid">31203292</pub-id></citation></ref>
<ref id="ref106"><label>106.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Fries</surname><given-names>JW</given-names></name> <name><surname>Sandstrom</surname><given-names>DJ</given-names></name> <name><surname>Meyer</surname><given-names>TW</given-names></name> <name><surname>Rennke</surname><given-names>HG</given-names></name></person-group>. <article-title>Glomerular hypertrophy and epithelial cell injury modulate progressive glomerulosclerosis in the rat</article-title>. <source>Lab Investig</source>. (<year>1989</year>) <volume>60</volume>:<fpage>205</fpage>&#x2013;<lpage>18</lpage>. PMID: <pub-id pub-id-type="pmid">2915515</pub-id></citation></ref>
<ref id="ref107"><label>107.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Cahill</surname><given-names>MM</given-names></name> <name><surname>Ryan</surname><given-names>GB</given-names></name> <name><surname>Bertram</surname><given-names>JF</given-names></name></person-group>. <article-title>Biphasic glomerular hypertrophy in rats administered puromycin aminonucleoside</article-title>. <source>Kidney Int</source>. (<year>1996</year>) <volume>50</volume>:<fpage>768</fpage>&#x2013;<lpage>75</lpage>. doi: <pub-id pub-id-type="doi">10.1038/ki.1996.375</pub-id>, PMID: <pub-id pub-id-type="pmid">8872950</pub-id></citation></ref>
<ref id="ref108"><label>108.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Fogo</surname><given-names>A</given-names></name> <name><surname>Hawkins</surname><given-names>EP</given-names></name> <name><surname>Berry</surname><given-names>PL</given-names></name> <name><surname>Glick</surname><given-names>AD</given-names></name> <name><surname>Chiang</surname><given-names>ML</given-names></name> <name><surname>MacDonell</surname><given-names>RC</given-names> <suffix>Jr</suffix></name> <etal/></person-group>. <article-title>Glomerular hypertrophy in minimal change disease predicts subsequent progression to focal glomerular sclerosis</article-title>. <source>Kidney Int</source>. (<year>1990</year>) <volume>38</volume>:<fpage>115</fpage>&#x2013;<lpage>23</lpage>. doi: <pub-id pub-id-type="doi">10.1038/ki.1990.175</pub-id>, PMID: <pub-id pub-id-type="pmid">2385079</pub-id></citation></ref>
<ref id="ref109"><label>109.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Osterby</surname><given-names>R</given-names></name> <name><surname>Gundersen</surname><given-names>HJ</given-names></name></person-group>. <article-title>Glomerular size and structure in diabetes mellitus. I. Early abnormalities</article-title>. <source>Diabetologia</source>. (<year>1975</year>) <volume>11</volume>:<fpage>225</fpage>&#x2013;<lpage>9</lpage>. doi: <pub-id pub-id-type="doi">10.1007/BF00422326</pub-id>, PMID: <pub-id pub-id-type="pmid">1149955</pub-id></citation></ref>
<ref id="ref110"><label>110.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Zerbini</surname><given-names>G</given-names></name> <name><surname>Bonfanti</surname><given-names>R</given-names></name> <name><surname>Meschi</surname><given-names>F</given-names></name> <name><surname>Bognetti</surname><given-names>E</given-names></name> <name><surname>Paesano</surname><given-names>PL</given-names></name> <name><surname>Gianolli</surname><given-names>L</given-names></name> <etal/></person-group>. <article-title>Persistent renal hypertrophy and faster decline of glomerular filtration rate precede the development of microalbuminuria in type 1 diabetes</article-title>. <source>Diabetes</source>. (<year>2006</year>) <volume>55</volume>:<fpage>2620</fpage>&#x2013;<lpage>5</lpage>. doi: <pub-id pub-id-type="doi">10.2337/db06-0592</pub-id>, PMID: <pub-id pub-id-type="pmid">16936212</pub-id></citation></ref>
<ref id="ref111"><label>111.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Trimarchi</surname><given-names>H</given-names></name> <name><surname>Barratt</surname><given-names>J</given-names></name> <name><surname>Cattran</surname><given-names>DC</given-names></name> <name><surname>Cook</surname><given-names>HT</given-names></name> <name><surname>Coppo</surname><given-names>R</given-names></name> <name><surname>Haas</surname><given-names>M</given-names></name> <etal/></person-group>. <article-title>Oxford classification of IgA nephropathy 2016: an update from the IgA nephropathy classification working group</article-title>. <source>Kidney Int</source>. (<year>2017</year>) <volume>91</volume>:<fpage>1014</fpage>&#x2013;<lpage>21</lpage>. doi: <pub-id pub-id-type="doi">10.1016/j.kint.2017.02.003</pub-id>, PMID: <pub-id pub-id-type="pmid">28341274</pub-id></citation></ref>
<ref id="ref112"><label>112.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Azevedo</surname><given-names>F</given-names></name> <name><surname>Alperovich</surname><given-names>G</given-names></name> <name><surname>Moreso</surname><given-names>F</given-names></name> <name><surname>Ibernon</surname><given-names>M</given-names></name> <name><surname>Goma</surname><given-names>M</given-names></name> <name><surname>Fulladosa</surname><given-names>X</given-names></name> <etal/></person-group>. <article-title>Glomerular size in early protocol biopsies is associated with graft outcome</article-title>. <source>Am J Transplant</source>. (<year>2005</year>) <volume>5</volume>:<fpage>2877</fpage>&#x2013;<lpage>82</lpage>. doi: <pub-id pub-id-type="doi">10.1111/j.1600-6143.2005.01126.x</pub-id>, PMID: <pub-id pub-id-type="pmid">16303000</pub-id></citation></ref>
<ref id="ref113"><label>113.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Schmitz</surname><given-names>A</given-names></name> <name><surname>Gundersen</surname><given-names>HJ</given-names></name> <name><surname>Osterby</surname><given-names>R</given-names></name></person-group>. <article-title>Glomerular morphology by light microscopy in non-insulin-dependent diabetes mellitus. Lack of glomerular hypertrophy</article-title>. <source>Diabetes</source>. (<year>1988</year>) <volume>37</volume>:<fpage>38</fpage>&#x2013;<lpage>43</lpage>. doi: <pub-id pub-id-type="doi">10.2337/diabetes.37.1.38</pub-id>, PMID: <pub-id pub-id-type="pmid">3335276</pub-id></citation></ref>
<ref id="ref114"><label>114.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Lane</surname><given-names>PH</given-names></name> <name><surname>Steffes</surname><given-names>MW</given-names></name> <name><surname>Mauer</surname><given-names>SM</given-names></name></person-group>. <article-title>Estimation of glomerular volume: a comparison of four methods</article-title>. <source>Kidney Int</source>. (<year>1992</year>) <volume>41</volume>:<fpage>1085</fpage>&#x2013;<lpage>9</lpage>. doi: <pub-id pub-id-type="doi">10.1038/ki.1992.165</pub-id></citation></ref>
<ref id="ref115"><label>115.</label><citation citation-type="journal"><article-title>How to read clinical journals: II. To learn about a diagnostic test</article-title>. <source>Can Med Assoc J</source>. (<year>1981</year>) <volume>124</volume>:<fpage>703</fpage>&#x2013;<lpage>10</lpage>. PMID: <pub-id pub-id-type="pmid">7471014</pub-id></citation></ref>
<ref id="ref116"><label>116.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Weibel</surname><given-names>ER</given-names></name> <name><surname>Gomez</surname><given-names>DM</given-names></name></person-group>. <article-title>A principle for counting tissue structures on random sections</article-title>. <source>J Appl Physiol</source>. (<year>1962</year>) <volume>17</volume>:<fpage>343</fpage>&#x2013;<lpage>8</lpage>. doi: <pub-id pub-id-type="doi">10.1152/jappl.1962.17.2.343</pub-id>, PMID: <pub-id pub-id-type="pmid">14005589</pub-id></citation></ref>
<ref id="ref117"><label>117.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Gundersen</surname><given-names>HJ</given-names></name> <name><surname>Jensen</surname><given-names>EB</given-names></name></person-group>. <article-title>The efficiency of systematic sampling in stereology and its prediction</article-title>. <source>J Microsc</source>. (<year>1987</year>) <volume>147</volume>:<fpage>229</fpage>&#x2013;<lpage>63</lpage>. doi: <pub-id pub-id-type="doi">10.1111/j.1365-2818.1987.tb02837.x</pub-id>, PMID: <pub-id pub-id-type="pmid">3430576</pub-id></citation></ref>
<ref id="ref118"><label>118.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Yoshida</surname><given-names>Y</given-names></name> <name><surname>Fogo</surname><given-names>A</given-names></name> <name><surname>Ichikawa</surname><given-names>I</given-names></name></person-group>. <article-title>Glomerular hemodynamic changes vs. hypertrophy in experimental glomerular sclerosis</article-title>. <source>Kidney Int</source>. (<year>1989</year>) <volume>35</volume>:<fpage>654</fpage>&#x2013;<lpage>60</lpage>. doi: <pub-id pub-id-type="doi">10.1038/ki.1989.35</pub-id>, PMID: <pub-id pub-id-type="pmid">2709670</pub-id></citation></ref>
<ref id="ref119"><label>119.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Pagtalunan</surname><given-names>ME</given-names></name> <name><surname>Drachman</surname><given-names>JA</given-names></name> <name><surname>Meyer</surname><given-names>TW</given-names></name></person-group>. <article-title>Methods for estimating the volume of individual glomeruli</article-title>. <source>Kidney Int</source>. (<year>2000</year>) <volume>57</volume>:<fpage>2644</fpage>&#x2013;<lpage>9</lpage>. doi: <pub-id pub-id-type="doi">10.1046/j.1523-1755.2000.00125.x</pub-id></citation></ref>
<ref id="ref120"><label>120.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Yoshida</surname><given-names>Y</given-names></name> <name><surname>Kawamura</surname><given-names>T</given-names></name> <name><surname>Ikoma</surname><given-names>M</given-names></name> <name><surname>Fogo</surname><given-names>A</given-names></name> <name><surname>Ichikawa</surname><given-names>I</given-names></name></person-group>. <article-title>Effects of antihypertensive drugs on glomerular morphology</article-title>. <source>Kidney Int</source>. (<year>1989</year>) <volume>36</volume>:<fpage>626</fpage>&#x2013;<lpage>35</lpage>. doi: <pub-id pub-id-type="doi">10.1038/ki.1989.239</pub-id></citation></ref>
<ref id="ref121"><label>121.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Thomas</surname><given-names>M</given-names></name> <name><surname>Lemaitre</surname><given-names>M</given-names></name> <name><surname>Wilson</surname><given-names>ML</given-names></name> <name><surname>Viboud</surname><given-names>C</given-names></name> <name><surname>Yordanov</surname><given-names>Y</given-names></name> <name><surname>Wackernagel</surname><given-names>H</given-names></name> <etal/></person-group>. <article-title>Applications of extreme value theory in public health</article-title>. <source>PLoS One</source>. (<year>2016</year>) <volume>11</volume>:<fpage>e0159312</fpage>. doi: <pub-id pub-id-type="doi">10.1371/journal.pone.0159312</pub-id>, PMID: <pub-id pub-id-type="pmid">27419853</pub-id></citation></ref>
<ref id="ref122"><label>122.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Lang</surname><given-names>T</given-names></name></person-group>. <article-title>Twenty statistical errors even you can find in biomedical research articles</article-title>. <source>Croat Med J</source>. (<year>2004</year>) <volume>45</volume>:<fpage>361</fpage>&#x2013;<lpage>70</lpage>. PMID: <pub-id pub-id-type="pmid">15311405</pub-id></citation></ref>
<ref id="ref123"><label>123.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Feinstein</surname><given-names>AR</given-names></name></person-group>. <article-title>X and iprP: an improved summary for scientific communication</article-title>. <source>J Chronic Dis</source>. (<year>1987</year>) <volume>40</volume>:<fpage>283</fpage>&#x2013;<lpage>8</lpage>. doi: <pub-id pub-id-type="doi">10.1016/0021-9681(87)90043-9</pub-id>, PMID: <pub-id pub-id-type="pmid">3558705</pub-id></citation></ref>
<ref id="ref124"><label>124.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Murray</surname><given-names>GD</given-names></name></person-group>. <article-title>The task of a statistical referee</article-title>. <source>Br J Surg</source>. (<year>1988</year>) <volume>75</volume>:<fpage>664</fpage>&#x2013;<lpage>7</lpage>. doi: <pub-id pub-id-type="doi">10.1002/bjs.1800750714</pub-id>, PMID: <pub-id pub-id-type="pmid">3046700</pub-id></citation></ref>
<ref id="ref125"><label>125.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Manabe</surname><given-names>S</given-names></name> <name><surname>Kataoka</surname><given-names>H</given-names></name> <name><surname>Mochizuki</surname><given-names>T</given-names></name> <name><surname>Iwadoh</surname><given-names>K</given-names></name> <name><surname>Ushio</surname><given-names>Y</given-names></name> <name><surname>Kawachi</surname><given-names>K</given-names></name> <etal/></person-group>. <article-title>Maximum carotid intima-media thickness in association with renal outcomes</article-title>. <source>J Atheroscler Thromb</source>. (<year>2021</year>) <volume>28</volume>:<fpage>491</fpage>&#x2013;<lpage>505</lpage>. doi: <pub-id pub-id-type="doi">10.5551/jat.57752</pub-id>, PMID: <pub-id pub-id-type="pmid">32759541</pub-id></citation></ref>
<ref id="ref126"><label>126.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Kataoka</surname><given-names>H</given-names></name> <name><surname>Watanabe</surname><given-names>S</given-names></name> <name><surname>Sato</surname><given-names>M</given-names></name> <name><surname>Manabe</surname><given-names>S</given-names></name> <name><surname>Makabe</surname><given-names>S</given-names></name> <name><surname>Akihisa</surname><given-names>T</given-names></name> <etal/></person-group>. <article-title>Predicting liver cyst severity by mutations in patients with autosomal-dominant polycystic kidney disease</article-title>. <source>Hepatol Int</source>. (<year>2021</year>) <volume>15</volume>:<fpage>791</fpage>&#x2013;<lpage>803</lpage>. doi: <pub-id pub-id-type="doi">10.1007/s12072-021-10176-9</pub-id></citation></ref></ref-list>
</back>
</article>