鎌状赤血球症における腎機能低下：レニン・アンジオテンシン系阻害薬との関連

Sickle cell disease (SCD) is associated with accelerated kidney function decline, with no proven effective therapies. We examined the associations between treatment with renin-angiotensin system inhibitors (RASi) and eGFR decline in SCD.

This 2-center observational study used electronic health record data of adult, Black patients with SCD (by hemoglobin electrophoresis) and ≥1 year follow-up between 2010-2024. We compared incident RASi users (exposure) to no treatment (reference). We created 1:1 propensity score-matched cohorts, balancing on demographics, vital signs, comorbidities, medications, and laboratory values. The primary endpoint was the difference in the mean change in eGFR per year, analyzing only chronic slopes (≥90 days post-index date) using linear mixed models on the matched cohorts. Sensitivity analyses were performed excluding patients with missing albuminuria and excluding low-dose RASi. Effect modification by SCD-modifying therapies was also examined.

Matched cohorts identified were primary analysis (358 patients), excluding missing albuminuria data (262 patients), and excluding low dose RASi (270 patients). All cohorts achieved optimal standardized mean differences < 0.2. After multivariable adjustment, there was no significant difference in eGFR decline between RASi and the reference in the primary cohort (-0.15 mL/min/year; 95% confidence interval [CI], -1.67 to +1.36; p = 0.84), the sensitivity analysis cohort excluding missing albuminuria data (+0.89 mL/min/year; 95% CI, -0.86 to +2.63; p = 0.32) and the sensitivity analysis cohort excluding low dose RASi (+0.78 mL/min/year; 95% CI, -1.12 to +2.67; p = 0.42). All p values for interaction terms between RASi and SCD-modifying therapies in all models were > 0.05.

In this large, real-world cohort of patients with SCD, RASi use was not associated with slowed eGFR decline. These findings underscore the limitations of observational data and highlight the urgent need for prospective trials to identify effective GFR-preserving therapies for this high-risk population.