ACE Inhibitor or ARB Therapy Can Prevent Diabetic Kidney Disease Progression

Do angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) reduce progression to end-stage kidney disease in patients with diabetic kidney disease?

Use of ACE inhibitor or ARB therapy reduces progression to end-stage kidney disease in patients with diabetic kidney disease.¹ (Strength of Recommendation: C, consensus, usual practice, disease-oriented evidence, case series for studies of treatment or screening, and/or opinion.) Neither ACE inhibitor nor ARB therapy has been associated with reduced all-cause or cardiovascular mortality compared with placebo in patients with diabetic nephropathy.

Family physicians routinely treat patients with diabetes and kidney disease. Diabetic kidney disease, or diabetic nephropathy, is defined by the presence of persistent albuminuria (less than 300 mg/day) on two separate occasions at least 3 months apart in patients with type 1 or 2 diabetes, with or without a reduced estimated glomerular filtration rate.^1,2 Diabetic nephropathy is the most common cause of end-stage kidney disease globally and is highly associated with poor cardiovascular outcomes.² End-stage kidney disease is defined as requiring kidney replacement therapy (eg, dialysis) or kidney transplantation.³ As a precursor to overt diabetic nephropathy, microalbuminuria (30–300 mg/day) is presented in this review as an important early indicator and clinical outcome pertinent to diabetic kidney disease.¹

This Cochrane review of 109 studies included 28,341 adults who had diabetic kidney disease and an estimated glomerular filtration rate greater than 15 mL/min per 1.73 m^2.1 Compared with placebo or no treatment, neither ACE inhibitor nor ARB therapy affected the clinical outcomes of all-cause mortality or cardiovascular death in patients with diabetic kidney disease. Included studies were predominantly randomized controlled trials conducted in the United States, India, Japan, and several other European and Asian countries. Most included studies were performed between 1990 and 2010. Findings from all studies contributed to the overall conclusions. Most studies evaluated patients with type 2 diabetes.

Compared with placebo or no treatment, ACE inhibitor and ARB therapy were associated with improved kidney outcomes in patients with diabetic kidney disease.¹ Specifically, ARB therapy prevented doubling of the serum creatinine level over 3 years (risk ratio [RR] = 0.84; 95% CI, 0.72–0.97; low-certainty evidence; NNT = 23 [95% CI, 13–125]) and progression from microalbuminuria to macroalbuminuria over 2 years (RR = 0.44; 95% CI, 0.23–0.85; low-certainty evidence; NNT = 5 [95% CI, 4–16]) compared with placebo or no therapy.

Included studies about ACE inhibitor therapy did not contain all of the same clinical outcomes (eg, doubling serum creatinine, progression of microalbuminuria to macroalbuminuria).¹ The authors noted that ACE inhibitor therapy reduced overall progression to kidney failure. Specifically, ACE inhibitors prevented progression from microalbuminuria to macroalbuminuria compared with placebo or no treatment over 2 years (RR = 0.43; 95% CI, 0.28–0.64; verylow-certainty evidence; NNT = 8 [95% CI, 7–13]). Notably, ACE inhibitors may contribute to regression of microalbuminuria (RR = 3.01; 95% CI, 1.86–4.88; very low-certainty evidence; NNT = 5 [95% CI, 3–12]). There was insufficient evidence to determine the comparative superiority of either ACE inhibitor or ARB therapy on kidney outcomes.