ACE-inhibitor use and the long-term risk of renal failure in diabetes

Abstract

The incidence of end-stage renal disease (ESRD) owing to diabetes has continued to increase despite the extensive use of angiotensin-converting enzyme (ACE) inhibitors to prevent diabetic nephropathy, primarily from evidence of short-term effectiveness. We assessed the long-term effect of ACE inhibitors on the risk of ESRD. We formed a population-based cohort of all diabetic patients treated with antihypertensive drugs in the Province of Saskatchewan, Canada, between 1982 and 1986. The patients were followed up to the end of 1997 to identify cases of end-stage renal failure. A nested case-control analysis was used with the controls matched to each case on age, diabetes type, and duration of follow-up. The cohort comprised 6102 subjects, of which the 102 cases who developed end-stage renal failure were matched to 4129 controls. Relative to thiazide diuretic use, the adjusted rate ratio of end-stage renal failure associated with the use of ACE inhibitors was 2.5 (95% confidence interval 1.3-4.7), whereas it was 0.8 (95% confidence interval 0.5-1.4) for beta-blockers and 0.7 (95% confidence interval 0.4-1.3) for calcium antagonists. The rate ratio of end-stage renal failure with the use of ACE inhibitors was 0.8 (95% confidence interval 0.3-2.5) during the first 3 years of follow-up, but increased to 4.2 (95% confidence interval 2.0-9.0) after 3 years. ACE-inhibitor use does not appear to decrease the long-term risk of end-stage renal failure in diabetes. Our data suggest instead that ACE inhibitors might actually increase this risk, which may possibly contribute to the continued increasing incidence of ESRD owing to diabetes.

Determinants and Changes Associated with Aldosterone Breakthrough after Angiotensin II Receptor Blockade in Patients with Type 2 Diabetes with Overt Nephropathy

“…Indeed, residual proteinuria is a predictor of progression to renal failure (6). However, despite RAAS blockade, many patients display high residual proteinuria levels and develop ESRD (7). It is possible that RAAS blockade strategies may be suboptimal, because serum aldosterone levels may increase during RAAS blockade with all ACEIs (8) or ARBs (9) tested so far.…”

Molecular Docking and Quantum Mechanical Studies on Pelargonidin-3-Glucoside as Renoprotective ACE Inhibitor

“…Inhibition of ACE results in the dwindled formation of angiotensin II and reduced catabolism of bradykinin, leading to systematic dilation of the arteries and veins and a decrease in arterial blood pressure. Inhibition of this enzyme also decreases the risk of end-stage renal disease (ESRD) in diabetics [3]. perindopril is a synthetic chemical drug which inhibits ACE; however, it causes dysfunctioning of the left ventricle of in Duchenne muscular dystrophy [4].…”

Angiotensin-converting enzyme inhibitors versus angiotensin receptor blockers for diabetic nephropathy: a retrospective comparison

“…The adjusted rate ratio for renal failure was 2.5 in patients initially treated with ACE inhibitors compared with patients treated with diuretics, when compared with the control patients. 24 This study has several limitations which need to be taken into consideration. First, there is no information on the indication for the medication in the patients, making bias by indication a major problem since it is possible that the ACE inhibitors were given to patients at particularly high risk for development of ESRD.…”