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Evidence summaries

Antihypertensive Agents for Preventing Diabetic Kidney Disease

Angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) are effective for the prevention of new onset diabetic kidney disease and death in normoalbuminuric people with diabetes. Level of evidence: "A"

A systematic review with network meta-analyses 2 assessing renal outcomes of renin-angiotensin system blockade in adults with diabetes (with or without proteinuria) included 71 trials with 103 120 participants. For the risk of progression of renal disease, no significant differences were detected between angiotensin-converting enzyme inhibitors (ACEi) and each of the remaining therapies: angiotensin receptor blockers (ARB) (OR 1.10; 95% CI 0.90 to 1.40), ACEi plus ARB (0.97; 95% CI 0.72 to 1.29), direct renin (DR) inhibitor plus ACEi (0.99; 95% CI 0.65 to 1.57), and DR inhibitor plus ARB (1.18; 95% CI 0.78 to 1.84). No significant differences were showed between ACEi and ARBs with respect to all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, angina pectoris, hospitalization for heart failure, end stage renal disease (ESRD), or doubling serum creatinine. Findings were limited by the clinical and methodological heterogeneity of the included studies.

Another meta-analysis 3 included 26 RCTs (20 for ACEi and 6 for ARB) with a total of 10 378 participants with diabetes and normoalbuminuria or any level of albuminuria. Compared to placebo, treatment with ACEi or ARB did not reduce all-cause mortality or CV. For renal outcomes, ARB significantly reduced the risk of ESRD by 23% (odds ratio 0.77, 95%CI 0.65 to 0.92), while ACEi were not associated with a decreased risk of ESRD (0.69, 0.43 to 1.10). Both ACEi and ARB reduced the risk of doubling of the serum creatinine level (0.60, 0.39 to 0.91 for ACEi; 0.75, 0.64 to 0.88 for ARB), and subgroup analyses for patients with macroalbuminuria or microalbuminuria showed similar results.

A Cochrane review [Abstract] 1 included 26 studies with a total of 61 264 subjects. CEi reduced the risk of new onset of microalbuminuria, macroalbuminuria or both when compared to placebo (RR 0.71, 95% CI 0.56 to 0.89; 8 studies, n=11 906), with similar benefits in people with and without hypertension (P = 0.74), and when compared to calcium channel blockers (RR 0.60, 95% CI 0.42 to 0.85; 5 studies, n=1 253). ACEi reduced the risk of death when compared to placebo (RR 0.84, 95% CI 0.73 to 0.97; 6 studies, n=11 350).

No effect was observed for ARB when compared to placebo for new microalbuminuria, macroalbuminuria or both (RR 0.90, 95% CI 0.68 to 1.19; 5 studies, n=7 653) or death (RR 1.12, 95% CI 0.88 to 1.41; 5 studies, n=7 653); however, meta-regression suggested possible benefits from ARB for preventing kidney disease in high risk patients. There was a trend towards benefit from use of combined ACEi and ARB for prevention of diabetic kidney disease compared with ACEi alone (RR 0.88, 95% CI 0.78 to 1.00; 2 studies, n=4 171).

The risk of cough was significantly increased with ACEi when compared to placebo (RR 1.84, 95% CI 1.24 to 2.72; 6 studies, n=11 791), however there was no significant difference in the risk of headache or hyperkalaemia. There was no significant difference in the risk of cough, headache or hyperkalaemia when ARB was compared to placebo.

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    References

    • Lv J, Perkovic V, Foote CV et al. Antihypertensive agents for preventing diabetic kidney disease. Cochrane Database Syst Rev 2012;(12):CD004136. [PubMed]
    • Catalá-López F, Macías Saint-Gerons D, González-Bermejo D et al. Cardiovascular and Renal Outcomes of Renin-Angiotensin System Blockade in Adult Patients with Diabetes Mellitus: A Systematic Review with Network Meta-Analyses. PLoS Med 2016;13(3):e1001971. [PubMed].
    • Wu HY, Huang JW, Lin HJ et al. Comparative effectiveness of renin-angiotensin system blockers and other antihypertensive drugs in patients with diabetes: systematic review and bayesian network meta-analysis. BMJ 2013;(347):f6008. [PubMed]

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