Effect of Statin Therapy on the Progression of Autosomal Dominant Polycystic Kidney Disease. A Secondary Analysis of the HALT PKD Trials

Abstract

Background Autosomal dominant polycystic kidney disease (ADPKD) commonly results in end-stage renal disease (ESRD), yet a long-term treatment that is well tolerated is still lacking. In a small randomized trial in children and adolescents pravastatin administration for 3 years was associated with reduced renal cyst growth, but no large trial has tested the effect of statins in adults. Methods We performed a post-hoc analysis of the HALT PKD trials to compare outcomes of participants who never used statins with those who used statin for at least 3 years. Because statins were not randomly allocated we used propensity score models with inverse probability of treatment weighting to account for imbalances between the groups. For subjects in Study A (preserved renal function, n=438) relevant outcomes were percent change in total kidney and liver volume and the rate of decline in estimated glomerular filtration rate (eGFR); for those in Study B (reduced renal function, n=352) we compared time to the composite endpoint of death, ESRD or 50% decline in eGFR. Follow-up was 5–8 years. Results There was no difference in any outcome between the 2 groups. However, limitations of this analysis are the small number of statin users in Study A, different statin drugs and doses used, non-randomized allocation and advanced disease stage in Study B. Conclusions Although this post-hoc analysis of the HALT PKD trials does not demonstrate a benefit of statin therapy, conclusions remain preliminary. A larger randomized trial in young people with ADPKD is necessary to answer the question whether statins can slow renal cyst growth and preserve kidney function.

Updated Canadian Expert Consensus on Assessing Risk of Disease Progression and Pharmacological Management of Autosomal Dominant Polycystic Kidney Disease

“…A post hoc analysis of the HALT-PKD study did not show differences in outcomes (percentage change in TKV for study A; composite of time to ESRD, death, or 50% reduction in eGFR for study B; and change in eGFR for both studies) between patients who never used statins and patients who used statins for at least 3 years. 55 Although this study did not demonstrate a benefit of statin therapy, it may be considered in cases where there are other indications for chronic kidney disease (CKD). Further studies are required to evaluate the benefits of statin therapy in patients with ADPKD.…”

International consensus statement on the diagnosis and management of autosomal dominant polycystic kidney disease in children and young people

“…Routine statin treatment for cardiovascular indications is more prevalent in adults than in children. A secondary analysis of the HALT-PKD trials reported no effect of self-reported statin use versus no statin use on TKV or composite end points in adults with ADPKD 116 . Therefore, the encouraging findings in the only controlled paediatric study of statin therapy in ADPKD published to date need to be balanced against the lack of evidence of beneficial effects on renal outcome in the uncontrolled adult study 116 and the lack of regulatory approval of statins for ADPKD.…”

Oxidative stress in autosomal dominant polycystic kidney disease: player and/or early predictor for disease progression?

“…Recently, because no large trials were available to test the effect of statins in adults, a post hoc analysis on the adults in the HALT-PKD trials, with 438 participants in group A (age 15-49 years, GFR > 60 mL/min/1.73 m 2 ) and 352 participants in group B (age 18-64 years, GFR 25-60 mL/min/1.73 m 2 ), was performed. Interestingly, no differences were found in any outcome between the two groups, which implies no potential benefit for the statin therapy in those populations [95].…”