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Antihypertensive agents for preventing diabetic kidney disease

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Abstract

Background

Twenty to sixty percent of diabetic patients are affected by hypertension and antihypertensive agents are used to treat this condition. These agents are also used to prevent the onset of kidney disease both in normotensive and hypertensive diabetics.

Objectives

To evaluate the comparative effects of antihypertensive agents in patients with diabetes and normoalbuminuria.

Search methods

MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, conference proceedings, and contact with investigators were used to identify relevant trials.

Selection criteria

Randomised controlled trials (RCTs) comparing any antihypertensive agent with placebo or another agent in hypertensive or normotensive patients with diabetes and no kidney disease (albumin excretion rate < 30 mg/d) were included.

Data collection and analysis

Two investigators independently extracted data on renal outcomes and other patient relevant outcomes (all‐cause mortality, serious cardiovascular events), and assessed quality of trials. Analysis was by a random effects model and results expressed as risk ratio (RR) and 95% confidence intervals (CI).

Main results

Sixteen trials (7603 patients) were identified, six of angiotensin converting enzyme inhibitors (ACEi) versus placebo, six of ACEi versus calcium channel blockers (CCBs), one of ACEi versus CCBs or combined ACEi and CCBs and three of ACEi versus other agents. Compared to placebo, ACEi significantly reduced the development of microalbuminuria (six trials, 3840 patients: RR 0.60, 95% CI 0.43 to 0.84) but not doubling of creatinine (three trials, 2683 patients: RR 0.81, 95% CI 0.24 to 2.71) or all‐cause mortality (four trials, 3284 patients: RR 0.81, 95% CI 0.64 to 1.03). Compared to CCBs, ACEi significantly reduced progression to microalbuminuria (four trials, 1210 patients: RR 0.58, 95% CI 0.40 to 0.84).

Authors' conclusions

A significant reduction in the risk of developing microalbuminuria in normoalbuminuric patients with diabetes has been demonstrated for ACEi only. It appears that the effect of ACEi is independent of baseline blood pressure, renal function and type of diabetes, but data is too sparse to be confident that these are not important effect modifiers and an individual patient data meta‐analysis is required.

Plain language summary

Angiotensin converting enzyme inhibitors (ACEi) were found to be effective for the primary prevention of kidney disease in patients with diabetes

Twenty to sixty percent of diabetic patients are affected by hypertension and antihypertensive agents are used to treat this condition. These agents are also used to prevent the onset of kidney disease both in normotensive and hypertensive diabetics. Twenty to 40% of patients with diabetic kidney disease progress to end‐stage renal disease (ESRD) while the rest may die from associated coronary artery disease or other cardiovascular causes before the onset of ESRD. This study was undertaken to determine the benefits and harms of antihypertensive treatment in patients with diabetes but who do not show signs of kidney disease. Sixteen trials (7603 patients) were identified comparing antihypertensive agents to placebo, no treatment and other antihypertensive agents. ACEi significantly reduced the development of urinary protein (a sign of kidney damage) compared to other agents, but did not reduce all‐cause mortality. More trials are needed that report the affect of antihypertensive agents on the prevention of kidney disease in diabetic patients.