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Abstract

Background: Diabetic nephropathy is part of the microvascular complication of diabetes mellitus along side neuropathy and retinopathy. Many mechanism has been presented as the pathophysiology of diabetic nephropathy but this could actually be attributed to the renin angiotensin system. The alteration in prorenin and renin homeostasis has been reported in patients with diabetes mellitus, it’s noticed to reduction in conversion of prorenin to renin there by leading to accumulation of prorenin binding to (pro)renin.

Aim: This article is targeted at explaining the contributory roles of the alteration in the prorenin and renin homeostasis in the pathogenesis of diabetic nephropathy and to explain why some the drugs that act along renin angiotensin pathways especially angiotensin receptor blockers can be very helpful in the management of diabetic nephropathy.

Methods: A careful literature search was made on some scientific databases such as PubMed, EMBase, Google Scholar, Research Gate and others using a very sensitive search strategy on researches that are related to effects of renin-angiotensin pathway on diabetic nephropathy focusing mainly on the use Handle Receptor Protein (HRP) and Angiotensin Receptor Blocker (ARB) in the management of diabetic nephropathy.

Results: The review of different articles shows HRP especially when use alongside Angiotensinogen Converting Enzyme Inhibitor (ACEI) increases plasma renin activities, reduces progression and development of glomeruli sclerosis, tubular injury, podocyte injury and proteinuria. Also, ARBs such as losartan and irbesartan was found to reduce relative risk for primary composite endpoint death of nephrons, serum creatinine level, and progression to endstage renal disease.

Conclusion: Binding of prorenin which accumulate in diabetic mellitus to (pro)renin receptor causes non-proteolytic activation at higher concentration and also release of profibrotic molecules which are injurious to the nephrons . This can be inhibited by the use of Handle Region Peptide (HRP) which is a competitive antagonist of prorenin or use of angiotensin receptor blocker which aid binding of angiotensin II to AT2 receptor leading to vasodilatory, antiinflammatory anti-proliferative, antihypertrophic and antifibrotic effects which antagonize those produced by prorenin.