Sacubitril/valsartan preserves kidney function in rats with cardiorenal syndrome after myocardial infarction

TL;DR

The drug Sacubitril/valsartan helps protect kidney function in rats with heart failure and kidney issues after a heart attack.

Contribution

This study shows that Sacubitril/valsartan preserves kidney function and reduces left atrial dilation in rats with cardiorenal syndrome.

Findings

Sacubitril/valsartan preserved renal function similarly to valsartan alone in rats with heart failure.

Sacubitril/valsartan uniquely reduced left atrial dilatation compared to valsartan and vehicle treatments.

Both treatments lowered mean arterial pressure compared to sham and vehicle groups.

Abstract

Renal dysfunction in heart failure increases mortality, limits treatment options and blunts responses to therapy. Angiotensin receptor-blocker and neprilysin inhibitors (ARNI) may preserve renal function by modulating both the renin-angiotensin-aldosterone system and the natriuretic peptide system. We investigated the renal effects of the ARNI Sacubitril/valsartan (Sac/Val) in rats with systolic dysfunction secondary to myocardial infarction. Male Sprague-Dawley rats underwent surgical MI induction and were randomized to six weeks of treatment with vehicle, valsartan or Sac/Val, and compared to sham operated animals. Renal function was evaluated by creatinine clearance, mean arterial pressure (MAP) by tail-cuff measurements, and cardiac function by magnetic resonance imaging and echocardiography. Vehicle treated animals developed cardiorenal syndrome, with impaired cardiac systolic function and mild renal dysfunction. Both valsartan and Sac/Val preserved renal function compared to vehicle (creatinine clearance mL/min [median with interquartile range]; sham 5.4 [4.8–6.0], vehicle 4.5 [4.1–5.1], valsartan 5.1 [5.1–5.5], Sac/Val 5.1 [5.0–5.6]; vehicle vs valsartan p = 0.034 and vehicle vs Sac/Val p = 0.044). MAP was reduced by both treatments compared to sham and vehicle groups (MAP mmHg; sham 131 [116–138], vehicle 123 [115–132], valsartan 108 [99–112], Sac/Val 111 [99–119]; sham vs valsartan p < 0.001 and sham vs Sac/Val p = 0.003, vehicle vs valsartan p = 0.006 and vehicle vs Sac/Val p = 0.041). Only Sac/Val reduced left atrial dilatation (diameter mm; sham 4.1 [3.7–4.4], vehicle 4.6 [3.8–5.6], valsartan 4.6 [4.1–5.5], Sac/Val 3.9 [3.6–4.5]; vehicle vs Sac/Val p = 0.047, valsartan vs Sac/Val p = 0.017) despite no improvement in systolic function in either treatment group. Sac/Val initiated in the acute post-MI phase preserved renal function to the same extent as valsartan alone and uniquely reduced left atrial dilatation, suggesting additional benefits beyond renoprotection in the setting of persistent systolic dysfunction.

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