Kidney disease is one of the leading causes of death and suffering in the 21st century. In 2017, the Global Burden of Disease (GBD) Chronic Kidney Disease Collaboration reported approximately 700 million cases worldwide and a 40% increase in prevalence over the past 30 years. In addition, chronic kidney disease (CKD) is projected to become the fifth leading cause of death globally by 2040.

One of the most common characteristics of kidney disease is the development and progressive increase of albuminuria/proteinuria, as well as tubulointerstitial injury, inflammation, and fibrosis. Recent findings have highlighted that, at the onset of kidney disease from various etiologies—during the subclinical stages—tubular changes may even precede alterations in glomerular structure and function. These observations have placed renal tubules at the center of the pathogenesis and progression of both acute and chronic kidney diseases.

Several cellular and molecular mechanisms have been proposed to mediate the development of tubulopathies. These include dysregulation of tubular epithelial cell turnover, cell senescence, autophagy/mitophagy, dedifferentiation, epithelial–mesenchymal transition, pro-inflammatory and pro-fibrotic phenotypes, as well as disruptions in the tubular metabolic state and various transport mechanisms. All of these processes are influenced by the modulation of autacoids, hormones, and inflammatory mediators within the tubular microenvironment. Despite advances in the field, the interactions among these factors remain poorly understood.

Regarding the treatment of kidney diseases, some of the cellular and molecular processes observed in various tubulopathies have been partially modulated by renin–angiotensin system (RAS) inhibitors—such as angiotensin receptor blockers and ACE inhibitors—sodium-glucose cotransporter 2 (SGLT2) inhibitors, and other promising compounds. These agents have also been shown to improve clinical outcomes in patients with kidney disease. However, their renoprotective effects are still not fully understood. Therefore, there is an urgent need to discover, design, and test new compounds that can prevent or even halt the development of tubulopathies and the progression of kidney disease.

This Research Topic aims to deepen our understanding of the complex pathophysiological mechanisms underlying different tubulopathies, as well as to discuss promising new pharmacotherapies, including their pharmacokinetics, pharmacodynamics, and safety under both physiological and pathological conditions. In this context, we welcome submissions of original research, systematic reviews, reviews, mini-reviews, hypotheses, clinical trials, theories, and perspectives addressing (but not limited to) the following topics:

- New pathophysiological mechanisms in tubulopathies, based on animal and/or human studies;

- Pharmacokinetic and pharmacodynamic studies of novel therapeutic agents for tubulopathies;

- Animal and/or human studies related to tubular injury in subclinical kidney disease;

- Studies showing the tubular damage as cause or consequence of progressive chronic glomerular dysfunction or injury;

- Studies showing renal tubules injury and dysfunction in the setting of acute kidney injury and chronic kidney disease;

- Studies involving new antiproteinuric agents;

- Innovative therapies for tubulopathies;

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Tubulopathies: Pathophysiological Insights and Advances in Therapeutic Strategies