The frequent use of imaging methods leads to increasing incidental diagnosis of small renal tumors (<7 cm). Partial nephrectomy is the preferred surgical treatment that often requires warm ischemia. This includes an increased risk of acute kidney injury and a higher cumulative risk of chronic kidney disease. We hypothesized that treatment with the combined AT1 receptor and neprilysin blocker (LCZ696) protects kidney function after partial nephrectomy. To test the hypothesis a pig model was employed.
Twenty female landrace pigs with a mean weight of 33kg (27-38) were enrolled and divided into 4 groups: 1) Partial nephrectomy+ LCZ696 49/51mg/day (N=6); 2), partial Nephrectomy+vehicle (N=6); 3) Control+ LCZ696(N=4); 4) Control+vehicle (N=4). Removal of one third of the kidney with 60min warm ischemia was performed in each surgery group. 99m Tc-DTPA GFR was measured at baseline and after 15 days. Urinary output and 99m Tc-DPTA clearance was measured during 4 hours at termination. Urine was collected form bladder at baseline and from right and left ureters at termination. Data were analyzed by two-way ANOVA with Tukey’s correction was using GraphPad 9.
Mean difference in urinary clearance of 99m TC-DPTA after surgery and Entresto® or vehicle was 24 ml/min (p=<0,05). In the group undergoing right partial nephrectomy and vehicle there was an increase in proteinuria from the injured kidney and albuminuria from both kidneys, while such increases were not reported in the group undergoing partial nephrectomy and treated with Entresto®
Treatment with LCZ696 was well tolerated, improved urinary clearance, and protected kidney filtration barrier after ischemia-reperfusion insult.LCZ696 could represent a novel therapy to protect kidney function after extended partial nephrectomy with prolonged warm ischemia time.