Molecular Mechanisms of Proteinuria

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Background

Persistent and increased leakage of protein in the urine (proteinuria) is abnormal. Circulating serum proteins are filtered by the glomerulus, and the small amount of protein that is present in the filtrate is passed through the glomerular capillary wall and reabsorbed by the proximal tubule. Although defects in tubular reabsorption of protein can also result in renal proteinuria (Fanconi’s syndrome), changes in glomerular permeability are what results in the most significant and highest urine protein concentrations. Thus, proteinuria is considered a key marker for renal dysfunction and characterizes the severity of the underlying kidney disease. Proteinuria is also an independent predictor for cardiovascular morbidity and mortality.

In the past twenty years, major progress in our understanding of the molecular mechanisms leading to the development of proteinuria was made. Spearheaded by the discovery that proteins located at the slit diaphragm of the glomerulus play a crucial role in the proper function of the glomerular filtration barrier, it has become clear that the molecular mechanisms leading to the development of proteinuria are complex.

Experimental basic research and clinical evidence, together with emerging clinical reports suggest the presence of a spectrum of disorders for which proteinuria is a typical occurrence. In addition, a plethora of published evidence support the presence of a salutary effect of reducing proteinuria. However, available studies do not offer unequivocal evidence in terms of treatment and benefits, given the complexity and heterogeneity of renal impairment encountered and, all considered, they share limitations that warrant discussion.

The primary focus of this topic edition is to identify different pathological components and molecular mechanisms contributing to the development of proteinuria in a variety of kidney diseases. Discerning the individual roles and impact of each component and mechanism can potentially lead to the identification of the best opportunities to intervene and improve patient outcomes.

Keywords: Proteinuria, kidney disease, molecular mechanisms, renal dysfunction

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