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Proteinuria and events beyond the slit

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Abstract

The origin of proteinuria is found in either the glomerular filtration device or the proximal tubular reabsorption machinery. During equilibrium, small amounts of predominantly low molecular weight proteins are filtered and reabsorbed by the receptor complex megalin/cubilin/amnionless. This results in a protein-free filtrate passing further down the tubule. During glomerular damage, the reabsorption machinery in the proximal tubule is challenged due to elevated amounts of proteins passing the glomerular filtration slits. Even though it is considered to be a high-capacity system, several conditions result in proteinuria, thus exposing the cells in the rest of the nephron to a protein-rich environment. The impact on cells in the more distal part of the nephron is uncertain, but studies support an involvement in fibrosis development. Protein accumulation in lysosomes of the proximal tubule, due to increased protein internalization, is thought to mediate inflammation and fibrosis, eventually leading to renal failure. In contrast, low molecular weight proteinuria develops when the endocytic machinery is malfunctioning either by direct or indirect causes such as in Imerslund-Gräsbeck syndrome (IGS) or Dent’s disease, respectively. This review discusses the origin of proteinuria and describes the structural fundament for protein reabsorption in the proximal tubule as well as conditions resulting in low molecular weight proteinuria.

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Abbreviations

IGS:

Imerslund-Gräsbeck syndrome

DB/FOAR:

Donnai-Barrow/facio-oculo-acoustico-renal

AMN:

Amnionless

LDL:

Low-density lipoprotein

RAP:

Receptor-associated protein

RBP:

Retinol-binding protein

DBP:

Vitamin-D-binding protein

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Acknowledgements

This work was supported by the University of Aarhus, Novo Nordisk Foundation, The Danish Medical Research Council, and programs of the European Community; EuReGene (FP6, GA#5085) and EUNEPHRON (FP7, GA#201590).

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Correspondence to Erik Ilsø Christensen.

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Nielsen, R., Christensen, E.I. Proteinuria and events beyond the slit. Pediatr Nephrol 25, 813–822 (2010). https://doi.org/10.1007/s00467-009-1381-9

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  • DOI: https://doi.org/10.1007/s00467-009-1381-9

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