The renin-angiotensin system in progression, remission and regression of chronic nephropathies.
Chronic proteinuric nephropathies may progress to end-stage renal disease (ESRD) through a series of events relatively independent of the initial insult that causes parenchymal damage when the injury involves a critical number of nephrons. The key event is enhanced glomerular capillary pressure, which, among other effects, impairs glomerular permeability to proteins, which reach the lumen of the proximal tubule. In this pathological process angiotensin II has a central role. Reabsorption of filtered proteins contributes to the interstitial injury by activating intracellular events, including upregulation of vasoactive and inflammatory genes. Both interstitial inflammation and progression of disease can be limited by angiotensin-converting enzyme (ACE) inhibitors that strengthen the glomerular permeability barrier to proteins, thus limiting proteinuria and filtered protein-dependent inflammatory signals. Clinical evidence suggests that remission is now achievable in some patients with chronic nephropathies. The current lag time between starting treatment and remission, however, is such that a substantial proportion of patients still progress to ESRD before their renal function begins to stabilize. A multimodal approach aimed at reducing or abolishing all the risk factors for progression may shorten the time to remission for the majority of patients with proteinuric nephropathies.
Aros
Claudio
C
Mario Negri Institute for Pharmacological Research, Unit of Nephrology and Dialysis, Ospedali Riuniti di Bergamo, 24128-Bergamo, Italy.
Remuzzi
Giuseppe
G
D000804:Angiotensin II; D000818:Animals; D002908:Chronic Disease; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology* / Q000628:therapy; D007678:Kidney Glomerulus; D007684:Kidney Tubules / Q000473:pathology; D011506:Proteins / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*
D011506:Proteins; D000804:Angiotensin II