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The UK HARP-III (UK Heart and Renal Protection-III) trial is comparing a novel angiotensin receptor-nepilysin inhibitor, sacubitril/valsartan with irbesartan (an angiotensin receptor blocker [ARB]).

Chronic kidney disease (CKD) affects about 1 in 10 adults. CKD is often a progressive condition and in some patients will eventually lead to end-stage renal disease (ESRD) requiring dialysis or transplantation. Inhibition of the renin-angiotensin system with angiotensin converting enzyme (ACE) inhibitors or ARBs have been shown to slow the rate of progression in proteinuric kidney disease. However, despite such treatments, a substantial residual risk of ESRD remains. There is therefore a need for treatments that can slow rate of the progression of CKD.

Neprilysin is the main enzyme responsible for degrading natriuretic peptides (ANP, BNP and CNP) and other vasodilatory peptides. Sacubitril/valsartan is a new treatment which has two actions: one half of the drug is an ARB (valsartan) and the other half of the drug is a neprilysin inhibitor (sacubitril) The drug has been shown to be superior to enalapril (an ACE inhibitor) in people with heart failure and animal data suggests it may also reduce renal progression, but no such human data exists.

The UK HARP-III trial is testing whether this new drug (sacubitril/valsartan) reduces the rate of decline in kidney function compared with current standard treatment (irbesartan). The results from UK HARP-III will help design a larger trial of sacubitril/valsartan (if shown to be safe) which could reliably test whether sacubitril/valsartan is better than current treatments in slowing the progression of kidney disease and protecting the heart in people with CKD.

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