Protein handling in kidney tubules

Abstract

The kidney proximal tubule reabsorbs and degrades filtered plasma proteins to reclaim valuable nutrients and maintain body homeostasis. Defects in this process result in proteinuria, one of the most frequently used biomarkers of kidney disease. Filtered proteins enter proximal tubules via receptor-mediated endocytosis and are processed within a highly developed apical endo-lysosomal system (ELS). Proteinuria is a strong risk factor for chronic kidney disease progression and genetic disorders of the ELS cause hereditary kidney diseases, so deepening understanding of how the proximal tubule handles proteins is crucial for translational nephrology. Moreover, the ELS is both an entry point for nephrotoxins that induce tubular damage and a target for novel therapies to prevent it. Cutting-edge research techniques, such as functional intravital imaging and computational modelling, are shedding light on spatial and integrative aspects of renal tubular protein processing in vivo, how these are altered under pathological conditions and the consequences for other tubular functions. These insights have potentially important implications for understanding the origins of systemic complications arising in proteinuric states, and might lead to the development of new ways of monitoring and treating kidney diseases.