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

[ Vol. 13 , Issue. 2 ]

Author(s):

Godela M. Brosnahan*, Kaleab Z. Abebe, Frederic F. Rahbari-Oskoui, Charity G. Patterson, Kyongtae T. Bae, Robert W. Schrier, William E. Braun, Arlene B. Chapman, Michael F. Flessner, Peter C. Harris, Ronald D. Perrone, Theodore I. Steinman, Vicente E. Torres and The HALT PKD Investigators   Pages 109 - 120 ( 12 )

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.

Keywords:

Autosomal dominant polycystic kidney disease, end-stage renal disease, glomerular filtration rate, HALT PKD trials, hydroxymethylglutaryl-CoA reductase inhibitors, total kidney volume.

Affiliation:

University of Colorado, Denver, Colorado CO, University of Pittsburgh, Pittsburgh, Pennsylvania PA, Emory University, Atlanta, Carolinas HealthCare System, Charlotte, North Carolina NC, University of Pittsburgh, Pittsburgh, Pennsylvania PA, University of Colorado, Denver, Colorado CO, Cleveland Clinic, Cleveland, Ohio OH, University of Chicago, Chicago, Illinois IL, National Institutes of Health, Bethesda, Maryland MD, Mayo Clinic, Rochester, Minnesota MN, Tufts Medical Center, Boston, Massachusetts MA, Beth Israel Deaconess Medical Center, Boston, Massachusetts MA, Mayo Clinic, Rochester, Minnesota MN

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