title: Proteinuria and progression of glomerular diseases.
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.
authors.affiliation: Division of Pediatric Nephrology, Children's Hospital of Pittsburgh, 530 45th Street 5th Floor, Office # 5129, Pittsburgh, PA 15201, USA. erkane@upmc.edu
authors.forename: Elif
authors.initials: E
authors.lastname: Erkan
mesh_terms: D000419:Albuminuria / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D018450:Disease Progression; D042241:Early Diagnosis; D006801:Humans; D007674:Kidney Diseases / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011237:Predictive Value of Tests; D011379:Prognosis
chemical_list: D015415:Biomarkers