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REVIEW article

Front. Med.
Sec. Nephrology
Volume 11 - 2024 | doi: 10.3389/fmed.2024.1478697
This article is part of the Research Topic The Role and Mechanism of Interstitial Microenvironment Alterations in Kidney Injury View all articles

TUBULOINTERSTITIAL INJURY IN PROTEINURIC CHRONIC KIDNEY DISEASES

Provisionally accepted
Giuseppe Remuzzi Giuseppe Remuzzi *Norberto Perico Norberto Perico Monica Cortinovis Monica Cortinovis *
  • Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy

The final, formatted version of the article will be published soon.

    Proteinuria is an independent risk factor for chronic kidney disease progression and cardiovascular diseases. Apart from its prognostic role, the load of proteins that pass across the disrupted glomerular capillary wall trigger multiple pathophysiologic processes. These include, among others, intratubular complement activation and excessive proximal tubular reabsorption of filtered proteins, especially albumin and albumin-bound free fatty acids, which can set off several pathways of cellular damage. The activation of these pathways can cause apoptosis of proximal tubular cells and paracrine effects that incite the development of interstitial inflammation and fibrosis, ultimately leading to irreversible kidney injury. In this review, we provide a comprehensive overview of the current understanding on the mechanisms underlying the tubular toxicity of ultrafiltered proteins in the setting of proteinuric chronic kidney diseases. The acquired knowledge is expected to be instrumental for the development of novel therapeutic classes of medications to be tested on top of standard of care with optimized renin-angiotensin-aldosterone blockade and sodium-glucose cotransporter-2 inhibition, in order to further improve the clinical outcomes of patients with proteinuric chronic kidney diseases.

    Keywords: Proteinuria, tubulointerstial injury, Chronic kidne disease, tubule toxicity, Fibrosis

    Received: 10 Aug 2024; Accepted: 14 Oct 2024.

    Copyright: © 2024 Remuzzi, Perico and Cortinovis. 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) or licensor 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.

    * Correspondence:
    Giuseppe Remuzzi, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy
    Monica Cortinovis, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy

    Disclaimer: 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.