What is the role of direct renin inhibitors in the treatment of diabetic nephropathy?

Updated: Oct 09, 2019
  • Author: Vecihi Batuman, MD, FASN; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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In a small double-blind, randomized, crossover trial, Persson et al observed the combination of aliskiren and irbesartan to be more antiproteinuric in type 2 diabetes mellitus than was monotherapy with either drug. [41] This study assessed the effect of aliskiren, a direct renin inhibitor, on proteinuria in patients with type 2 DM (n = 26) and compared the effect with that of placebo, irbesartan (an ARB), and the combination of aliskiren and irbesartan.

Patients were assigned to four 2-month treatments in random order. Monotherapy with either aliskiren or irbesartan significantly improved albuminuria when compared with placebo. Combination therapy with aliskiren and irbesartan reduced albuminuria by 71%, more than did either monotherapy (aliskiren monotherapy 48%; irbesartan monotherapy 58%). Use of direct renin inhibitors with ARBs or ACEIs is no longer recommended. This after the FDA issued an advisory in April 2012 based on deliterios serious side effects when such combinations were used.

Research suggests that vitamin D may have a role in renin inhibition and that vitamin D supplementation may be useful in reducing proteinuria in patients with diabetic nephropathy. Patients with diabetic nephropathy with stage 3 chronic kidney disease (eGFR 59 – 30 mL/min/1.73 m2) or more advanced stages should be evaluated for their vitamin D and parathyroid hormone status as recommended by the National Kidney Foundation- Kidney Disease Dialysis Outcomes Quality Initiative (NKF-KDOQI). [42] If vitamin D levels are low, patients should be given vitamin D supplementation. One randomized controlled trial suggested that vitamin D supplementation may reduce proteinuria in patients with diabetic nephropathy. [43, 44]

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