Treatment effects of renin-angiotensin aldosterone system blockade on kidney failure and mortality in chronic kidney disease patients

BACKGROUND Chronic kidney disease (CKD) is a leading cause of death before and after onset of end-stage renal disease (ESRD). Knowing treatments that can delay disease progression will lead to reduced mortality. We therefore aimed to estimate the effectiveness of renin angiotensin aldosterone system (RAAS) blockade on CKD progression. METHODS We conducted a retrospective CKD cohort at Ubon Ratchathani province, Thailand from 1997 to 2011. ESRD was defined as estimated glomerular filtration rate (eGFR) <15 ml/min/1.73 m2, dialysis, or kidney transplantation. All-cause mortality was verified until December 31, 2011. A counterfactual-framework was applied to estimate the effectiveness of RAAS blockade on outcomes, i.e., ESRD, death before and after ESRD. RAAS blockade was categorized according to duration of use <0.25 year, 0.25-1 year (RAAS1), and >1 year (RAAS2). An augmented inverse-probability weighting (AIPW) method was used to estimate potential-outcome mean (POM) and average treatment-effect (ATE). Multi-logit and Poisson regressions were used for treatment and outcome models, respectively. Analyses were stratified by ESRD, death before/after ESRD for diabetic and non-diabetic groups. STATA 14.0 was used for statistical analyses. RESULTS Among 15,032 diabetic patients, 2346 (15.6%), 2351 (18.5%), and 1607 (68.5%) developed ESRD, died before ESRD, and died after ESRD, respectively. Only RAAS2 effect was significant on ESRD, death before and after ESRD. The ESRD rates were 12.9%, versus 20.0% for RAAS2 and non-RAAS, respectively, resulted in significant risk differences (RD) of -7.2% (95% CI: -8.8%, -5.5%), and a numbers needed-to-treat (NNT) of 14. Death rates before ESRD for these corresponding groups were 14.4% (12.9%, 15.9%) and 19.6% (18.7%, 20.4%) with a NNT of 19. Death rates after ESRD in RAAS2 was lower than non-RASS group (i.e., 62.8% (55.5%, 68.9%) versus 68.1% (65.9%, 70.4%)) but this was not significant. RAAS2 effects on ESRD and death before ESRD were persistently significant in non-diabetic patients (n = 17,074) but not for death after ESRD with the NNT of about 15 and 16 respectively. CONCLUSIONS Receiving RAAS blockade for 1 year or longer could prevent both CKD progression to ESRD and premature mortality.