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Optimal nephroprotection: use, misuse and misconceptions about blockade of the renin-angiotensin system. Lessons from the ONTARGET and other recent trials.

Abstract：

:Results from the ONTARGET trial remind us that acute haemodynamically mediated renal dysfunction, triggered by low arterial pressure or volume depletion, can occur in high-risk cardiovascular patients (who usually have some degree of diseased intrarenal vessels) treated with renin-angiotensin system (RAS) blockers (especially in combination). However, nephroprotection could not be properly assessed in the trial, as the population was at low renal risk. Although albuminuria remains a useful marker in many patients, it can neither predict acute renal dysfunction nor replace end-stage renal disease (ESRD) as the endpoint in clinical trials. Recent trials using surrogate endpoints suggest that some RAS blockers (ACE inhibitors, angiotensin receptor blockers, the renin inhibitor aliskiren) may be more nephroprotective than others, but proving this requires comparing them (alone or in combination) in populations with identified renal disease (mainly diabetic nephropathy) and the use of hard endpoints. RAS-blocker dosages are critical: as some patients need much larger doses to decrease proteinuria than do others, the efficacy of a high-dose RAS blocker needs to be assessed in patients with persistent proteinuria. In patients with massive proteinuria despite maximum RAS-blocker dosages, combination RAS blockade should be considered by nephrologists, but will require close monitoring of renal function; also, the treatment needs to be withdrawn (at least temporarily) as soon as volume depletion or excessively low arterial pressure arises. In recent trials, lowering blood pressure towards values recommended by the current guidelines (130/80mmHg) has reduced microvascular (lower levels of urinary albumin excretion) and macrovascular events in diabetic patients.

journal_name

Diabetes Metab

journal_title

Diabetes & metabolism

authors

Halimi JM,Asmar R,Ribstein J

doi

10.1016/j.diabet.2009.05.003

subject

Has Abstract

pub_date

2009-12-01 00:00:00

pages

425-30

issue

eissn

1262-3636

issn

1878-1780

pii

S1262-3636(09)00144-X

journal_volume

pub_type

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Optimal nephroprotection: use, misuse and misconceptions about blockade of the renin-angiotensin system. Lessons from the ONTARGET and other recent trials.