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Chronic kidney disease, heart failure and neprilysin inhibition

Richard Haynes1,2, Doreen Zhu2, Parminder K Judge1,2

  • 1Medical Research Council Population Health Research Unit, University of Oxford, Headington, Oxford, UK.

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
|April 28, 2019
PubMed

Insights

Neprilysin inhibition (sacubitril/valsartan) did not improve kidney function in patients with advanced kidney disease. However, it reduced cardiac biomarkers, suggesting potential cardiovascular benefits needing further investigation in larger trials.

Area of Science:

  • Nephrology
  • Cardiology
  • Pharmacology

Background:

  • Patients with chronic kidney disease (CKD) face elevated cardiovascular disease (CVD) risk, often presenting as heart failure (HF).
  • Conversely, HF patients frequently exhibit impaired kidney function, highlighting the intricate cardiorenal link.
  • Management guidelines for HF are robust, yet patients with advanced CKD are often excluded from pivotal trials.

Purpose of the Study:

  • To evaluate the efficacy of neprilysin inhibition in improving kidney function in patients with advanced CKD.
  • To assess the impact of neprilysin inhibition on cardiovascular biomarkers in this population.
  • To investigate the potential of neprilysin inhibition for managing cardiorenal conditions.

Main Methods:

  • The UK HARP-III trial investigated neprilysin inhibition (sacubitril/valsartan) versus irbesartan in patients with advanced kidney disease.
  • Short- to medium-term effects on kidney function and cardiovascular biomarkers were assessed.
  • Randomized controlled trial design was employed to compare treatment arms.

Main Results:

  • Neprilysin inhibition showed no significant improvement in kidney function compared to the irbesartan control group.
  • Allocation to neprilysin inhibition led to a greater reduction in cardiac biomarkers than irbesartan.
  • These findings suggest a potential cardiovascular benefit of neprilysin inhibition in advanced CKD.

Conclusions:

  • Neprilysin inhibition does not appear to enhance kidney function in patients with advanced CKD.
  • The observed reduction in cardiac biomarkers warrants further investigation into cardiovascular outcome benefits.
  • Larger clinical outcome trials are necessary to confirm the efficacy of neprilysin inhibition for cardiorenal patients.

Keywords:
CKDblood pressurecardiovascularheart failurerenin-angiotensin system

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