Potential effects and application prospect of angiotensin receptor-neprilysin inhibitor in diabetic kidney disease.

Diabetic kidney disease (DKD) is one of the main causes of end-stage renal disease (ESRD) and all-cause mortality in diabetic patients, despite the extensive use of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB). Angiotensin receptor-neprilysin inhibitor (ARNI), combining ARB and neutral endopeptidase inhibitor (NEPI), is likely to have potential favorable effects in DKD. This review summarizes existing preclinical and clinical studies on mechanism of ARNI and its potential effects on DKD. In preclinical studies, ARNI manifested its renoprotective effects by improving natriuresis, ameliorating inflammation, oxidative stress and renal dysfunction, and slowing down glomerulosclerosis and tubulointerstitial injury of kidney, but its effect on proteinuria is still controversial. Beneficial effects of ARNI on blood glucose regulation and glycometabolism have also been reported. There are no clinical studies of ARNI that specifically focus on DKD patients so far. ARNI has application potential in DKD, but there still need clinical studies that focus on DKD patients to determine its effectiveness, safety and underlying mechanism.