Spironolactone Improves Renoprotection in Patients with Diabetes and Hypertension

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Adding spironolactone to a regimen that includes maximal ACE inhibition improves renoprotection in patients with diabetic nephropathy, data suggest.

The finding is based on a placebo-controlled, double-blind trial involving 81 hypertensive diabetics who had albuminuria (urine albumin-to-creatinine ratio of 300 mg/g or higher) and were taking the ACE inhibitor lisinopril (80 mg once daily). The investigators noted that they used a supramaximal dose of lisinopril to ensure that add-on therapy would reflect effects beyond what is achievable with ACE inhibition alone.

Robert D. Toto, MD, and colleagues at the University of Texas Southwestern Medical Center in Dallas, randomly assigned patients to receive placebo, losartan (100 mg daily), or spironolactone (25 mg daily) for 48 weeks.

Compared with the placebo group, the spironolactone-treated patients experienced a significant 34% decrease in urine albumin-to-creatinine ratio, the researchers reported in the Journal of the American Society of Nephrology (2009;20:2641-2650). The losartan group had a nonsignificant 16.8% decrease. Clinic and ambulatory BP, glycemic control, creatinine clearance, and sodium and protein intake did not differ among the groups.

The addition of spironolactone was associated with a greater incidence of hyperkalemia, and the authors noted that this condition can cause serious cardiotoxicity. Clinicians should be cautious whenever using drugs that block the renin-angiotensin-aldosterone system (RAAS) to manage patients with diabetes and kidney disease, “especially when using combinations of drugs that block the RAAS at multiple sites,” they wrote.

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