Title:Determinants of Progression in Early Autosomal Dominant Polycystic Kidney Disease: Is it Blood Pressure or Renin-Angiotensin-Aldosterone-System Blockade?
VOLUME: 14 ISSUE: 1
Author(s):Godela M. Brosnahan*, Kaleab Z. Abebe, Charity G. Moore, Kyongtae T. Bae, William E. Braun, Arlene B. Chapman, Michael F. Flessner, Peter C. Harris, Marie C. Hogan, Ronald D. Perrone, Frederic F. Rahbari-Oskoui, Theodore I. Steinman, Vicente E. Torres and The HALT PKD Investigators
Affiliation:University of Colorado Denver, Aurora, Colorado, CO, University of Pittsburgh, Pittsburgh, Pennsylvania, PA, University of Pittsburgh, Pittsburgh, Pennsylvania, PA, University of Pittsburgh, Pittsburgh, Pennsylvania, PA, Cleveland Clinic, Cleveland, Ohio, OH, University of Chicago, Chicago, Illinois, IL, National Institutes of Health, Bethesda, Maryland, MD, Mayo Clinic, Rochester, Minnesota, MN, Mayo Clinic, Rochester, Minnesota, MN, Tufts Medical Center, Boston, Massachusetts, MA, Emory University, Atlanta, Beth Israel Deaconess Medical Center, Boston, Massachusetts, MA, Mayo Clinic, Rochester, Minnesota, MN
Keywords:Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, autosomal dominant polycystic kidney
disease, estimated glomerular filtration rate, HALT PKD trials, total kidney volume.
Abstract:Background: The HALT PKD trial in early autosomal dominant polycystic kidney disease
(ADPKD) showed that intensive control of systolic blood pressure to 95-110 mmHg was associated
with a 14% slower rate of kidney volume growth compared to standard control. It is unclear
whether this result was due to greater blockade of the renin-angiotensin-aldosterone system
(RAAS) by allowing the use of higher drug doses in the low blood pressure arm, or due to the lower
blood pressure per se.
Methods: In this secondary analysis of HALT PKD Study A, we categorized participants into high
and low dose groups based on the median daily equivalent dose of RAAS blocking drugs used after
the initial dose titration period. Using linear mixed models, we compared the percent change in total
kidney volume and the slope of estimated glomerular filtration rate (eGFR) between the 2 groups.
We also assessed the effects of time-varying dose and time-varying blood pressure parameters on
these outcomes.
Results: Subjects in the high dose group (n=252) did not experience a slower increase in total kidney
volume than those in the low-dose (n=225) group, after adjustment for age, sex, genotype, and
BP arm. The chronic slope of eGFR decline was similar in the 2 groups. Higher time-varying systolic
blood pressure was associated with a steeper decline in eGFR.
Conclusion: ADPKD progression (as detected by eGFR decline and TKV increase) was ameliorated
by intense blood pressure control as opposed to pharmacologic intensity of RAAS blockade.
