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Protective effect of sacubitril/valsartan (Entresto®) on kidney function and filtration barrier injury in a porcine model of partial nephrectomy.
Nephrology, Dialysis, Transplantation 2022 June 16
Kidney surgery often includes organ ischemia with risk of acute kidney injury. The present study tested if treatment with combined angiotensin II-AT1 receptor and neprilysin blocker Entresto® (LCZ696-sacubitril/valsartan) protects filtration barrier and kidney function after ischemia and partial nephrectomy in pigs. Single kidney glomerular filtration rate (GFR) by technetium-99m-diethylene-triamine-pentaasetate ([99mTc]Tc-DTPA) clearance was validated (n = 6). Next, four groups of pigs were followed for 15 days (n = 24) after: 1) Partial nephrectomy (1/3 right kidney, 60 min ischemia) + Entresto® (49/51 mg/day, n = 8); 2) partial nephrectomy + vehicle (n = 8); 3) sham + Entresto® (49/51 mg/day, n = 4); 4) sham + vehicle (n = 4). GFR, diuresis, and u-albumin were measured at baseline and from each kidney after 15 days. The sum of single kidney GFR (25 ± 6 mL/min, right and 31 ± 7 mL/min, left) accounted for total GFR (56 ± 14 mL/min). Entresto® had no effect on baseline blood pressure, p-creatinine, midregional pro atrial natriuretic peptide (MR-proANP), heart rate, and diuresis. After 15 days, Entresto® increased GFR in the uninjured kidney (+23 ± 6 mL/min, P < 0.05) and reduced albuminuria from both kidneys. In the sham group, plasma MR-proANP was not altered by Entresto®; it increased to similar levels 2 hours after surgery with and without Entresto®. Fractional sodium excretion increased by Entresto®. Kidney histology and kidney injury molecule-1 in cortex tissue were not different. In conclusion, Entresto® protects the filtration barrier and increases the functional adaptive response of the uninjured kidney.
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