Pathophysiology of Proteinuria and Its Value as an Outcome Measure in Chronic Kidney Disease

Br J Clin Pharmacol. 2013 Oct;76(4):516-23. doi: 10.1111/bcp.12104.

Abstract

Chronic kidney diseases share common pathogenic mechanisms that, independently from the initial injury, lead to glomerular hyperfiltration, proteinuria, and progressive renal scarring and function loss. Consistent experimental evidence supports the crucial role of proteinuria in accelerating kidney disease progression to end-stage renal failure through multiple pathways, including induction of tubular chemokine expression and complement activation. These events, in turn, lead to inflammatory cell infiltration in the interstitium and sustained fibrogenesis. The extent of proteinuria is widely recognized as a marker of the severity of chronic kidney disease and as a predictor of future decline in glomerular filtration rate. More importantly, a reduction in proteinuria invariably translates into a protection from renal function decline in patients with diabetic and non-diabetic renal disease. Recent evidence also showed the existence of a relationship between proteinuria levels and cardiovascular risk, which extends to the range of urinary albumin excretion that was previously thought 'normal'. Thus, proteinuria should be considered a valuable surrogate end point for clinical trials in patients with chronic renal diseases and a target for reno- and cardioprotecive strategies.

Keywords: biomarker; cardiovascular; chronic kidney disease; proteinuria.

Publication types

  • Review

MeSH terms

  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / urine
  • Chemokines / biosynthesis
  • Complement Activation / physiology
  • Glomerular Filtration Rate / physiology
  • Humans
  • Kidney Tubules / immunology
  • Kidney Tubules / metabolism
  • Kidney Tubules / pathology
  • Proteinuria / etiology*
  • Proteinuria / metabolism
  • Proteinuria / urine
  • Renal Insufficiency, Chronic / complications*
  • Renal Insufficiency, Chronic / metabolism
  • Renal Insufficiency, Chronic / physiopathology
  • Renal Insufficiency, Chronic / urine
  • Risk Factors

Substances

  • Chemokines