Sacubitril/valsartan reduces proteinuria depending on blood pressure in patients with stage 4-5 chronic kidney disease

Background: Blood pressure (BP) control is an important factor in the management of chronic kidney disease (CKD). Several studies have shown that BP in many patients with CKD remained uncontrolled even with multiple medications. Sacubitril/valsartan, an angiotensin receptor neprilysin inhibitor (ARNI), has been newly approved for treating hypertension in Japan. However, the renoprotective effects remain unclear, particularly in patients with advanced CKD. Here, we investigated the effects on proteinuria of this ARNI in patients with stage 4-5 CKD. Methods: We retrospectively collected data from outpatients with stage 4-5 CKD who started ARNI from January until December 2023. The primary outcome was the change in urine protein creatinine ratio (UPCR) at 6 months after ARNI initiation. Secondary outcomes were systolic and diastolic BP, estimated glomerular filtration rate (eGFR), serum potassium, and serum uric acid (UA). We analyzed factors associated with 50% UPCR reduction by multivariate analysis. Results: In total, 47 patients were analyzed. ARNI reduced UPCR from 2.14 g/gCr (interquartile range; 1.09-2.91) to 1.05 g/gCr (0.42-1.95; p < 0.001). Systolic BP fell from 150.0 mmHg (139.5-160.0) to 134.0 mmHg (124.5-140.0; p < 0.001). No significant changes in eGFR, serum potassium, and serum uric acid were observed, except for a slight decrease in eGFR among patients with conversion from a renin-angiotensin system inhibitor to ARNI. In multivariate regression analysis, higher systolic BP (per 10-mmHg increase) was significantly associated with reduced proteinuria (odds ratio 2.51, 95% confidence interval 1.35-4.66; p = 0.004). Conclusions: ARNI reduced proteinuria in patients with stage 4-5 CKD, particularly for those with uncontrolled hypertension.