The impact of angiotensin-receptor neprilysin inhibitors on cardiovascular events and solute transport function in peritoneal dialysis patients: a multicenter retrospective controlled study.

BACKGROUND: Whether angiotensin receptor-neprilysin inhibitor (ARNI) can reduce the incidence of cardiovascular events and improve peritoneal function in peritoneal dialysis (PD) patients remains unclear. Thus, this study aims to clarify the role of ARNI in PD patients. METHODS: This was a multicenter retrospective study. A total of 102 patients were enrolled for analysis. Patients who continuously used ARNI for 12 months were assigned to the ARNI group (n = 55), while those who never used ARNI to the control group (n = 47). Clinical indicators and cardiovascular risk factors were analyzed, along with in vitro experiments on neoangiogenesis to investigate the underlying molecular mechanisms of peritoneal protection by ARNI. RESULTS: Systolic blood pressure (p = 0.001), diastolic blood pressure (p = 0.001), and left ventricular ejection fraction (p = 0.008) were statistically improved after 12 months of ARNI therapy, whereas these metrics did not change in control patients. The risk factors for the occurrence of cardiac events in PD patients included the use of ARNI [hazard ratio (HR) 0.053; 95% confidence interval (CI), 0.006-0.492] and NT-proBNP level (HR 2.317; 95% CI, 1.179-4.554). Additionally, there was a decrease in 4-hour ratio of creatinine concentration in dialysate to plasma (4h Scr D/P) in the ARNI group (p = 0.020). The in vitro experiments showed that LCZ696, a combination of sacubitril and valsartan, inhibited neoangiogenesis via the VEGFR2/ERK1/2 and Notch1 pathways. CONCLUSIONS: ARNI may play a protective role in reducing the incidence of cardiovascular events and decreasing solute transport in PD patients.