Combined renin-angiotensin-aldosterone system blockade and statin therapy effectively reduces the risk of cerebrovascular accident in autosomal dominant polycystic kidney disease: a nationwide population-based cohort study.

Pei-Hsun Sung,Hon-Kan Yip,John Y Chiang,Yao-Hsu Yang,Hsin-Ju Chiang,Mel S Lee

doi:10.18632/oncotarget.18636

Abstract

Fairly limited data reported the incidence and risk of cerebrovascular accident (CVA) in autosomal dominant polycystic kidney disease (ADPKD). Additionally, little is known regarding the therapeutic impact of renin-angiotensin-aldosterone system (RAAS) blockade and statin on reducing the occurrence of CVA in ADPKD. We utilized the data from Taiwan National Health Insurance Research Database (NHIRD) to perform a population-based cohort study (1997-2013). A total of 2,647 patients with ADPKD were selected from 1,000,000 general population after excluding patients with age<18, renal replacement therapy and concomitant diagnosis of CVA. Additionally, non-ADPKD subjects were assigned as comparison group by matching study cohort with age, gender, income and urbanization in 1:10 ratio (n=26,470). The results showed that ADPKD group had significantly higher frequency rate and cumulative incidence of CVA as compared with the non-ADPKD group (8.73% v.s. 3.93%, p<0.0001). Furthermore, the frequencies of both hemorrhagic and ischemic strokes were also significantly higher in the ADPKD than non-ADPKD group (all p-values <0.0001). After adjusting for age, gender and atherosclerotic risk factors with multivariate analysis, ADPKD independently carried 2.34- and 5.12-fold risk for occurrence of CVA and hemorrhagic stroke (95% CI: 2.02-2.72 and 4.01-6.54), respectively. Combination therapy [adjusted (a) HR=0.19, 95% CI: 0.11-0.31] was superior to either RAAS blockade (aHR=0.37, 95% CI, 0.28-0.5) or statin (aHR=0.44, 95% CI, 0.24-0.79) alone for reducing the CVA occurrence in the ADPKD population. In conclusion, ADPKD was associated with an increased risk of CVA occurrence. Combined RAAS blockade and statin therapy effectively reduces the risk of CVA in ADPKD.

Highlights

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease that affects 1/1,000 to 1/400 individuals worldwide [1, 2], and accounts for 8-10% of patients with end-stage renal disease (ESRD) in the Western countries [3]
Yoo et al has further reported that the patients with ADPKD on maintenance dialysis have around threefold risk for intracranial hemorrhage (ICH) [11]
60.26% and 26.52% of ADPKD patients were on the treatment with renin-angiotensin-aldosterone system (RAAS) blockade and statin, respectively, which had significantly higher prescription rate than general population

Summary

Introduction

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease that affects 1/1,000 to 1/400 individuals worldwide [1, 2], and accounts for 8-10% of patients with end-stage renal disease (ESRD) in the Western countries [3]. These patients have been found around threefold mortality rate compared with general population [4] if lacks of appropriate treatment. Current guidelines [10] have recommended to carefully screen ADPKD patients with family history of ICA or SAH, previous ICA rupture, and high risk professions. Feasible therapeutic modalities that could reduce the occurrence of CVA in ADPKD remain unclear

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