Maintenance of the plasma potassium (K+) level within normal physiological range (3.5–5.0 mM) is crucial for the proper function of excitable and non-excitable cells. This homeostatic challenge is met by the tight coordination of K+ storage occurring mainly in skeletal muscle and K+ excretion via the kidneys (and, to a lesser extent, the colon). In the kidney, K+ secretion takes place in the distal nephron and is mediated by ROMK and Big-K (BK) channels. Additionally, K+ reabsorption, mediated by HKATPase II, occurs in the distal nephron under physiological conditions, such as decreased dietary K+, hypokalemia, and gestation. Despite the relevance of ROMK, BK, and HKATPaseII in potassium handling in the distal nephron, little is known about their implications in human disorders. Recently, ROMK has been shown to exhibit an altered apical localization in familial hyperkalemic hypertension, while the implication of BK and HKATPaseII in pathological conditions involving the distal nephron is still poorly understood.
With such a narrow physiological range, dyskalemia is common. A recent population study revealed a rising trend of hypokalemia in the USA population from 3% in 1999 to 11% in 2016, making it an increasingly common health condition. Based on the key role of plasma K+ in setting the resting membrane potential of excitable tissues, hypokalemia causes skeletal muscle and myocardium dysfunction. However, hypokalemia is also associated with several disorders in non-excitable tissues, mainly the kidney. Indeed, mild dietary K+ deficiency is associated with salt-sensitive hypertension, while severe hypokalemia is associated with hypokalemic nephropathy, and nephrogenic diabetes insipidus. Moreover, hypokalemia is a risk factor for the progression of chronic kidney diseases. Despite extensive literature exploring several areas of the physiopathology of hypokalemia-associated disorders, the direct role of decreased extracellular K+ and the pathophysiologic cascades are still not fully understood.
Conversely, hyperkalemia is also increasing in the population, particularly in patients suffering chronic kidney disease where it could negatively impact their cardiac function. The development of hyperkalemia can be explained by the fact that some CKD patients maintain their K+ balance (equilibrium between K+ input and output) to the detriment of the plasma K+ level. Hyperkalemia is correlated to a higher mortality rate by cardiovascular events and its occurrence is a cause of
discontinuation or suppression of the renin-angiotensin-aldosterone system (RAAS) inhibitor medications with bad consequences on the progression of the disease. Therefore, the search for pharmacological tools that would help lowering plasma K+ value in such patients is of primary importance.
In this present Research Topic, we would like to expand the field with basic, translational, clinical, and applied research exploring, but are not limited to, these areas:
• Mechanisms regulating renal or colonic K+ excretion.
• Mechanisms regulating renal K+ reabsorption along the distal nephron.
• Physiopathology of hypokalemia-associated disorders.
• Integrated mechanisms of the K+ homeostasis in physiological and pathological states
• Studies using small animals, (such as Zebrafish, Drosophila, and C. elegans) as models for renal K+ homeostasis, are welcome.
Maintenance of the plasma potassium (K+) level within normal physiological range (3.5–5.0 mM) is crucial for the proper function of excitable and non-excitable cells. This homeostatic challenge is met by the tight coordination of K+ storage occurring mainly in skeletal muscle and K+ excretion via the kidneys (and, to a lesser extent, the colon). In the kidney, K+ secretion takes place in the distal nephron and is mediated by ROMK and Big-K (BK) channels. Additionally, K+ reabsorption, mediated by HKATPase II, occurs in the distal nephron under physiological conditions, such as decreased dietary K+, hypokalemia, and gestation. Despite the relevance of ROMK, BK, and HKATPaseII in potassium handling in the distal nephron, little is known about their implications in human disorders. Recently, ROMK has been shown to exhibit an altered apical localization in familial hyperkalemic hypertension, while the implication of BK and HKATPaseII in pathological conditions involving the distal nephron is still poorly understood.
With such a narrow physiological range, dyskalemia is common. A recent population study revealed a rising trend of hypokalemia in the USA population from 3% in 1999 to 11% in 2016, making it an increasingly common health condition. Based on the key role of plasma K+ in setting the resting membrane potential of excitable tissues, hypokalemia causes skeletal muscle and myocardium dysfunction. However, hypokalemia is also associated with several disorders in non-excitable tissues, mainly the kidney. Indeed, mild dietary K+ deficiency is associated with salt-sensitive hypertension, while severe hypokalemia is associated with hypokalemic nephropathy, and nephrogenic diabetes insipidus. Moreover, hypokalemia is a risk factor for the progression of chronic kidney diseases. Despite extensive literature exploring several areas of the physiopathology of hypokalemia-associated disorders, the direct role of decreased extracellular K+ and the pathophysiologic cascades are still not fully understood.
Conversely, hyperkalemia is also increasing in the population, particularly in patients suffering chronic kidney disease where it could negatively impact their cardiac function. The development of hyperkalemia can be explained by the fact that some CKD patients maintain their K+ balance (equilibrium between K+ input and output) to the detriment of the plasma K+ level. Hyperkalemia is correlated to a higher mortality rate by cardiovascular events and its occurrence is a cause of
discontinuation or suppression of the renin-angiotensin-aldosterone system (RAAS) inhibitor medications with bad consequences on the progression of the disease. Therefore, the search for pharmacological tools that would help lowering plasma K+ value in such patients is of primary importance.
In this present Research Topic, we would like to expand the field with basic, translational, clinical, and applied research exploring, but are not limited to, these areas:
• Mechanisms regulating renal or colonic K+ excretion.
• Mechanisms regulating renal K+ reabsorption along the distal nephron.
• Physiopathology of hypokalemia-associated disorders.
• Integrated mechanisms of the K+ homeostasis in physiological and pathological states
• Studies using small animals, (such as Zebrafish, Drosophila, and C. elegans) as models for renal K+ homeostasis, are welcome.
