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

Phisitt Vejakama,Atiporn Ingsathit,Mark Mcevoy,Gareth J Mckay,Ammarin Thakkinstian,Alexander P Maxwell,John Attia

doi:10.1186/s12882-017-0753-9

Phisitt Vejakama, Atiporn Ingsathit + Show 5 more

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https://doi.org/10.1186/s12882-017-0753-9

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Abstract

BackgroundChronic 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.MethodsWe 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.ResultsAmong 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.ConclusionsReceiving RAAS blockade for 1 year or longer could prevent both CKD progression to ESRD and premature mortality.

Highlights

Chronic kidney disease (CKD) is a leading cause of death before and after onset of end-stage renal disease (ESRD)
Our results suggest that use of renin angiotensin aldosterone system (RAAS) blocking drugs for longer than 1 year in patients with CKD reduces major clinical outcomes, i.e., ESRD progression and death prior ESRD onset in both diabetic and non-diabetic patients
For every 100 diabetic and non-diabetic subjects with CKD being treated with RAAS blockers for longer than 1 year, approximately 14 and 7 cases of ESRD, 5 and 6 deaths before ESRD will be prevented over 4.5 years

Summary

Introduction

Chronic kidney disease (CKD) is a leading cause of death before and after onset of end-stage renal disease (ESRD). We aimed to estimate the effectiveness of renin angiotensin aldosterone system (RAAS) blockade on CKD progression. Chronic kidney disease (CKD) is one of the leading noncommunicable diseases contributing to morbidity and mortality globally. Estimates of age-standardized mortality from the Global Burden of Disease 2013 study have ranked CKD highest in terms of years of life lost for any non-communicable cause of premature death between the years 1990 and 2013 [7]. Current guidelines identify individuals with CKD as being at high risk for cardiovascular disease (CVD) and other adverse outcomes and that individuals who succumb to end-stage renal disease (ESRD) have a very high mortality, often as a consequence of accelerated CVD [8]. The primary therapeutic options to prevent and treat CKD are blood pressure control, mainly through renin angiotensin aldosterone system (RAAS) blockade, i.e. angiotensin converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), combined with improved glycemic control

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