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

• Type of Material: Article
• Authors: Godela M. Brosnahan, University of Colorado; Kaleab Z. Abebe, University of Pittsburgh; Frederic Rahbari Oskoui, Emory University; Charity G. Patterson, Carolinas HealthCare System; Kyongtae T. Bae, University of Pittsburgh; Robert W. Schrier, University of Colorado; William E. Braun, Cleveland Clinic; Arlene B Chapman, Emory University; Michael F. Flessner, National Institutes of Health; Peter C. Harris, Mayo Clinic; Ronald D. Perrone, Tufts Medical Center; Theodore I. Steinman, Beth Israel Deaconess Medical Center; Vicente E. Torres, Mayo Clinic
• Language: English
• Date: 2017
• Publisher: Bentham Science Publishers
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 Bentham Science Publishers
• Final Published Version (URL): http://dx.doi.org/10.2174/1573402113666170427142815
• Title of Journal or Parent Work: Current Hypertension Reviews
• ISSN: 1573-4021
• Volume: 13
• Issue: 2
• Start Page: 109
• End Page: 120
• Grant/Funding Information: Mutation analysis was supported by DK62410-S1 to Dr. Harris and the Mayo Translational PKD Center (DK090728).; Supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (DK62402 to Dr. Schrier, DK62411 to Dr. Perrone, DK62410 to Dr. Torres, DK082230 to Dr. Moore, DK62408 to Dr. Chapman, and DK62401 to Washington University in St. Louis) and the National Center for Research Resources General Clinical Research Centers (RR000039 to Emory University, RR000585 to the Mayo Clinic, RR000054 to Tufts Medical Center, RR000051 to the University of Colorado, RR023940 to the University of Kansas Medical Center, and RR001032 to Beth Israel Deaconess Medical Center), National Center for Advancing Translational Sciences Clinical and Translational Science Awards (RR025008 and TR000454 to Emory University, RR024150 and TR00135 to the Mayo Clinic, RR025752 and TR001064 to Tufts University, RR025780 and TR001082 to the University of Colorado, RR025758 and TR001102 to Beth Israel Deaconess Medical Center, RR033179 and TR000001 to the University of Kansas Medical Center, and RR024989 and TR000439 to Cleveland Clinic), by funding from the Zell Family Foundation (to the University of Colorado), and by a grant from the PKD Foundation.
• Keywords: hydroxymethylglutaryl-CoA reductase inhibitors; HALT PKD trials; end-stage renal disease; total kidney volume; glomerular filtration rate; Autosomal dominant polycystic kidney disease

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. CONCLUSION: 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.