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Proteinuria and progression of glomerular diseases

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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.

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Authors and Affiliations

  1. Division of Pediatric Nephrology, Children’s Hospital of Pittsburgh, 530 45th Street 5th Floor, Office # 5129, Pittsburgh, PA, 15201, USA

    Elif Erkan

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Correspondence to Elif Erkan.

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Questions

1) What is the most common cause of end-stage renal disease during adolescence?

a) Obstructive nephropathy

b) Diabetes mellitus

c) Polycystic kidney disease

d) Glomerulonephritis

2) Which one of these is not considered as a ligand of megalin?

a) Vitamin D binding protein

b) Retinol-binding protein

c) Albumin

d) Vit B12

3) What is the mechanism/epithelial cell type responsible for internalization of albumin?

a)Pinocytosis/proximal tubule

b) Caveolin-mediated endocytosis/distal tubule

c) Receptor-mediated endocytosis/proximal tubule

d) Diffusion/proximal tubule

4) In which of these diseases has microalbuminuria been implicated as a marker for renal damage?

a) Diabetes mellitus

b) Autosomal dominant polycystic kidney disease

c) Sickle cell anemia

d) All of the above

5) A 15-year-old male patient has had a history of insulin-dependent diabetes mellitus for 7 years. His 24-h urine albumin excretion is 130 μg/min (normal: 20–200). His HbA1c is 9 %. BUN: 15 mg/dl, creatinine 0.7 mg/dl. Blood pressure: 130/70 mmHg. The rest of the physical exam is unremarkable. What would be your recommendation?

a) Follow-up in 6 months

b) Restrict salt intake

c) Tight blood glucose control and start the patient on an ACE inhibitor

d) Increase physical activity

Answers

1-d

2-d

3-c

4-d

5-c, d

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Erkan, E. Proteinuria and progression of glomerular diseases. Pediatr Nephrol 28, 1049–1058 (2013). https://doi.org/10.1007/s00467-012-2335-1

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  • DOI: https://doi.org/10.1007/s00467-012-2335-1

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