Introduction: Aldosterone seems to have deleterious effects on the kidneys. Many animal studies and few clinical trials now have shown that suppression of aldosterone by aldosterone receptor blockers ameliorated these effects.

Method: In a double-blind, cross over study, 24 patients with diabetic nephropathy who were already receiving either ACE inhibitor(lisinopril 20-40 mg/day ) or ARB( losartan 25-100 mg/day )were given spironolactone( 25 mg during the first month and 50 mg during the second and third month if serum K remained ok) or matching placebo with 1 month of washout in between. All patients were from a single center and exclusively male veterans. Blood pressure, serum creatinine, serum K and spot urine protein/creatinine were measured at the beginning and end of each study period. The study was started in May of 2003 and completed in May 2006.

Result: Of 30 patients who were randomized 6 patients did not complete the study. Data were analyzed on the 24 patients who completed the study . The mean systolic BP on placebo was 149.9mmHg(s.d. 20.5) and 150.9(s.d. 24.7)at the beginning and at the end of 3 months study period. Diastolic BP was 76.9 (13.9) and 79.2 (13.6) respectively(p=0.103 and 0.502); mean BP on spironolactone was systolic 152.0(23.8) and 140.1(17.2) at the beginning and at the end (p=.002). Diastolic BP during spironolactone therapy was 80.16(112.3) and 76.1(9.7) respectively (p=0.092). The urine pr/cr increased from 1.24(1.13) to 1.54 (2.1) while on placebo and decreased from 1.83(1.83) to 0.79(0.9) during spironolactone period. (p=0.218 for placebo and p=.007 for spironolactone). In other words proteinuria increased by 24% during the placebo treatment period while decreased by half ( 57% ) during the active treatment. Mean serum K did not change during the period of placebo treatment. (4.3(0.48) to 4.3(0.43) but went from 4.3(0.47) to 4.6(0.56) during spironolactone therapy (p=0.023).

Conclusion: Addition of a modest dose of spironolactone to a regimen of ace inhibitor or ARB in patients with diabetic proteinuria causes further reduction in proteinuria and also lowers the systolic BP.