Tubular toxicity of proteinuria and the progression of chronic kidney disease
Makhammajanov Z. Gaipov A. Myngbay A. Bukasov R. Aljofan M. Kanbay M.
1 April 2024Oxford University Press
Nephrology Dialysis Transplantation
2024#39Issue 4589 - 599 pp.
Proteinuria is a well-established biomarker of chronic kidney disease (CKD) and a risk predictor of associated disease outcomes. Proteinuria is also a driver of CKD progression toward end-stage kidney disease. Toxic effects of filtered proteins on proximal tubular epithelial cells enhance tubular atrophy and interstitial fibrosis. The extent of protein toxicity and the underlying molecular mechanisms responsible for tubular injury during proteinuria remain unclear. Nevertheless, albumin elicits its toxic effects when degraded and reabsorbed by proximal tubular epithelial cells. Overall, healthy kidneys excrete over 1000 individual proteins, which may be potentially harmful to proximal tubular epithelial cells when filtered and/or reabsorbed in excess. Proteinuria can cause kidney damage, inflammation and fibrosis by increasing reactive oxygen species, autophagy dysfunction, lysosomal membrane permeabilization, endoplasmic reticulum stress and complement activation. Here we summarize toxic proteins reported in proteinuria and the current understanding of molecular mechanisms of toxicity of proteins on proximal tubular epithelial cells leading to CKD progression.
albuminuria , chronic kidney disease , proteinuria , renal tubular toxicity , tubulointerstitial fibrosis
Text of the article Перейти на текст статьи
Department of Biomedical Sciences, School of Medicine, Nazarbayev University, Astana, Kazakhstan
Department of Medicine, School of Medicine, Nazarbayev University, Astana, Kazakhstan
Clinical Academic Department of Internal Medicine, CF “University Medical Center”, Astana, Kazakhstan
Department of Biology, School of Sciences and Humanities, Nazarbayev University, Astana, Kazakhstan
Department of Chemistry, School of Sciences and Humanities, Nazarbayev University, Astana, Kazakhstan
Division of Nephrology, Department of Internal Medicine, Koc University, Istanbul, Turkey
Department of Biomedical Sciences
Department of Medicine
Clinical Academic Department of Internal Medicine
Department of Biology
Department of Chemistry
Division of Nephrology
10 лет помогаем публиковать статьи Международный издатель
Книга Публикация научной статьи Волощук 2026 Book Publication of a scientific article 2026