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Pediatric Nephrology

, Volume 28, Issue 7, pp 1049–1058 | Cite as

Proteinuria and progression of glomerular diseases

  • Elif Erkan
Educational Review

Abstract

One of the major challenges of nephrology is to develop therapeutic strategies to halt the progression of kidney diseases. In clinical settings, nephrotic-range proteinuria correlates with the rate of progression, particularly in glomerular diseases. Hence, the degree of proteinuria has been utilized to monitor the response to treatment as well as to predict outcome. However, the pathophysiology of proteinuria-induced progression remains unknown. Albumin accounts for the majority of the protein in nephrotic urine and as a result of this clinical observation studies have focused on understanding the adverse effects of albumin overload in the kidney. Albumin is internalized by receptor-mediated endocytosis in proximal tubule cells via low density lipoprotein (LDL) type receptor, megalin. Albumin at high concentrations mimicking nephrotic milieu has resulted in the upregulation of pro-inflammatory/fibrogenic genes and apoptosis in proximal tubule cells in in vivo and in vitro models of albumin overload. These properties of albumin on proximal tubule cells may explain extensive tubulointerstitial fibrosis and tubular atrophy observed in end-stage kidney disease. In addition to tubular toxicity, podocytes respond to proteinuric states by cytoskeletal alterations and loss of the differentiation marker synaptopodin. Identifying the molecular network of proteins involved in albumin handling will enable us to manipulate the specific signaling pathways and prevent damage caused by proteinuria.

Keywords

Proteinuria Progression Kidney disease Microalbuminuria 

Notes

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Copyright information

© IPNA 2012

Authors and Affiliations

  1. 1.Division of Pediatric NephrologyChildren’s Hospital of PittsburghPittsburghUSA

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