Effect of Dual Blockade of Renin-Angiotensin Aldosterone System on Proteinuria in Patients with Diabetic Nephropathy and Advanced Azotemia

Purpose: To investigate the dual effect of angiotensin blockade by irbesartan and enalapril on proteinuria in diabetic patients with azotemia.
Methods: Patients with diabetes of > 5 years duration, proteinuria at a nephrotic level and serum creatinine > 1.5 mg/dL were enrolled in the study. Forty-five enrolled patients were divided into three groups, those receiving enalapril , irbesartan, or enalapril plus irbesartan, respectively, over a period of 24 weeks. Urinary protein excretion and serum level of albumin, creatinine, potassium were measured before and after treatment
Results: In patients receiving enalapril, irbesartan, and both drugs concomitantly, mean urinary protein excretion level decreased significantly at the end of 6 months from 6.46 ± 4.66 to 3.36 ± 1.60, 5.89 ± 5.34 to 3.22 ± 1.72 and 5.99 ± 3.77 to 2.10 ± 2.22 g/day, respectively (p = 0.001). Decrease in proteinuria in the group receiving the combined therapy was more significant than the other two groups (p = 0.025). During the period of therapy, serum albumin increased and mean arterial pressure decreased significantly (p = 0.02 and p = 0.002, respectively) but serum creatinine and potassium and creatinine clearance values showed insignificant increases (p = 0.28 and p = 0.57, respectively).
Conclusion: The combined use of enalapril and irbesartan, in patients with diabetic nephropathy associated with azotemia, is more effective in decreasing proteinuria without causing any substantial increase in serum potassium levels. The combined use of these two drugs shows a more pronounced anti-proteinuric effect.

Keywords
Angiotensin-converting enzyme inhibitor; Angiotensin receptor blocker; Diabetic nephropathy; Azotemia; Proteinuria; Aldosterone; Renin; Blood pressure