Patterns of Kidney Function Decline in Autosomal Dominant Polycystic Kidney Disease: A Post Hoc Analysis From the HALT-PKD Trials

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  • Additional Information
    • Affiliation:
      1 University of Colorado Denver, Aurora, CO
      2 University of Pittsburgh, Pittsburgh, PA
      3 Emory University, Atlanta, GA
      4 University of Kansas Medical Center, Kansas City, KS
      5 Cleveland Clinic, Cleveland, OH
      6 University of Chicago, Chicago, IL
      7 National Institutes of Health, Bethesda, MD
      8 Mayo Clinic, Rochester, MN
      9 Tufts Medical Center, Boston, MA
      10 Beth Israel Deaconess Medical Center, Boston, MA
    • Note:
      Complete author and article information (including a list of the members of the HALT-PKD Trial Investigators) provided before references.
      HALT-PKD Trial Investigators: Beth Israel Deaconess Medical Center: Theodore Steinman, MD, Jesse Wei, MD, Peter Czarnecki, MD, Ivan Pedrosa, MD; Cleveland Clinic Foundation: William Braun, MD, Saul Nurko, MD, Erick Remer, MD; Emory University: Arlene Chapman, MD, Diego Martin, MD, PhD, Frederic Rahbari-Oskoui, MD, MS, Pardeep Mittal, MD; Mayo Clinic: Vicente Torres, MD, PhD, Marie C. Hogan, MD, PhD, Ziad El-Zoghby, MD, Peter Harris, PhD, James Glockner, MD, PhD, Bernard King Jr, MD; Tufts Medical Center: Ronald Perrone, MD, Neil Halin, DO, Dana Miskulin, MD; University of Colorado: Robert Schrier, MD, Godela Brosnahan, MD, Berenice Gitomer, PhD, Cass Kelleher, MD, Amirali Masoumi, MD, Nayana Patel, MD; University of Kansas Medical Center: Franz Winklhofer, MD, Jared Grantham, MD,† Alan Yu, MB, BChir, Connie Wang, MD, Louis Wetzel, MD; University of Pittsburgh (Data Coordinating Center): Charity G. Moore, PhD, MSPH, James E. Bost, PhD, Kyongtae Bae, MD, Kaleab Z. Abebe; Washington University in St. Louis (Data Coordinating Center): J. Philip Miller, PhD, Paul A. Thompson; National Institutes of Health (NIH): Josephine Briggs, MD, Michael Flessner, MD, Catherine M. Meyers, MD, and Robert Star, MD. Data and Safety Monitoring Committee: James Shayman, MD, (Chair), William Henrich, MD, (Former Chair), Tom Greene, PhD, Mary Leonard, MD, MSCE, Peter McCullough, MD, PhD, Sharon Moe, MD, Michael Rocco, MD, and David Wendler, PhD. †Deceased.
      Authors’ Full Names and Academic Degrees: Godela M. Brosnahan, MD, Kaleab Z. Abebe, PhD, Charity G. Moore, PhD, Frederic F. Rahbari-Oskoui, MD, Kyongtae T. Bae, MD, PhD, Jared J. Grantham, MD,† Robert W. Schrier, MD, William E. Braun, MD, Arlene B. Chapman, MD, Michael F. Flessner, MD, PhD, Peter C. Harris, PhD, Marie C. Hogan, MD, PhD, Ronald D. Perrone, MD, Dana C. Miskulin, MD, Theodore I. Steinman, MD, and Vicente E. Torres, MD, PhD, on behalf of the HALT-PKD Trial Investigators. †Deceased.
      Authors’ Contributions: Research idea and study design: GMB (for original HALT-PKD trials: RWS, JJG, ABC, VET, RDP, WEB, TIS, MFF); data acquisition: GMB, RWS, ABC, KTB, MCH, DCM, VET, RDP, WEB, TIS, FFR-O; data analysis/interpretation: GMB, JJG, VET, RDP, WEB, PCH, KTB, FFR-O, MFF; statistical analysis: KZA, CGM. JJG died before the manuscript was submitted; GMB affirms that he contributed to data interpretation and vouches for his coauthorship status; all authors approved the final author list. Except as noted, each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved.
      Support: 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 PKD Center at the University of Colorado for various clinical studies including HALT), and the Polycystic Kidney Disease Foundation provided financial support to the clinical centers and recruitment assistance for the enrollment phase of HALT-PKD (from 2006-2009). Mutation analysis was supported by DK62410-S1 to Dr Harris and the Mayo Translational PKD Center (DK090728). Study drugs were donated by Boehringer Ingelheim Pharmaceuticals Inc (telmisartan and matched placebo) and Merck & Co Inc (lisinopril). For the primary report of the HALT-PKD trials (published in N Engl J Med in 2014), individuals at the National Institutes of Health participated in the study design, interpretation of the data, and writing of the report. For this article, aside from Dr Flessner’s authorship role, the funders had no role in the design, data collection, interpretation, and writing of the current secondary analysis or decision to submit the manuscript for publication.
      Financial Disclosure: Dr Schrier reports having received fees for serving on advisory boards from Otsuka Pharmaceuticals, Janssen Pharmaceuticals, and Ikaria; Dr Perrone reports consulting fees from Sanofi–Genzyme and Vertex Pharmaceuticals and consulting fees and grant support through his institution from Otsuka Pharmaceuticals; Drs Torres and Harris report grant support from Otsuka Pharmaceuticals; Dr Steinman reports grant support from Kadmon, Fibrogen, and AMAG Pharmaceuticals and a consulting fee from Sanofi-Genzyme; Dr Rahbari-Oskoui reports fees for serving on advisory boards from Otsuka, Kadmon, and Astute medical and also research support from Otsuka; Dr Bae reports consulting fees from Kadmon Pharmaceuticals; Dr Chapman reports consulting fees from Kadmon, Otsuka Pharmaceuticals, and Pfizer and grant support from Otsuka Pharmaceuticals; and Dr Hogan reports receiving grant support from Novartis. The other authors declare that they have no other relevant financial interests.
    • Keywords:
      Autosomal dominant polycystic kidney disease (ADPKD)
      Bayesian models
      end-stage renal disease (ESRD)
      estimated glomerular filtration rate (eGFR)
      eGFR trajectory
      eGFR slope
      total kidney volume
      mutation analysis
      kidney disease progression
    • Abstract:
      Background Previous clinical studies of autosomal dominant polycystic kidney disease (ADPKD) reported that loss of kidney function usually follows a steep and relentless course. A detailed examination of individual patterns of decline in estimated glomerular filtration rate (eGFR) has not been performed.
    • Abstract:
      Setting & Participants 494 HALT-PKD Study A participants (younger; preserved eGFR) and 435 Study B participants (older; reduced eGFR) who had more than 3 years of follow-up and 7 or more eGFR assessments.
    • Abstract:
      Measurements Longitudinal eGFR assessments using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation.
    • Abstract:
      Predictors Demographic, clinical, laboratory, and imaging features of participants.
    • Abstract:
      Outcomes Probability of linear and nonlinear decline patterns or of stable eGFR calculated for each participant from a Bayesian model of individual eGFR trajectories.
    • Abstract:
      Results Most (62.5% in Study A and 81% in Study B) participants had a linear decline in eGFR during up to 8 years of follow-up. A proportion (22% in Study A and 13% in Study B) of progressors had a nonlinear pattern. 15.5% of participants in Study A and 6% in Study B had a prolonged (≥4.5 years) period of stable eGFRs. These individuals (Study A) had significantly smaller total kidney volumes, higher renal blood flows, lower urinary albumin excretion, and lower body mass index at baseline and study end. In Study B, participants with reduced but stable eGFRs were older than the progressors. Two-thirds of nonprogressors in both studies had PKD1 mutations, with enrichment for weak nontruncating mutations.
    • Abstract:
      Limitations Relatively short follow-up of a clinical trial population.
    • Abstract:
      Conclusions Although many individuals with ADPKD have a linear decline in eGFR, prolonged intervals of stable GFRs occur in a substantial fraction. Lower body mass index was associated with more stable kidney function in early ADPKD.
    • ISSN:
      0272-6386
    • Accession Number:
      10.1053/j.ajkd.2017.10.023
    • Accession Number:
      S0272638617310971
    • Copyright:
      © 2017 by the National Kidney Foundation, Inc.
  • Citations
    • ABNT:
      STEINMAN, T. et al. Patterns of Kidney Function Decline in Autosomal Dominant Polycystic Kidney Disease: A Post Hoc Analysis From the HALT-PKD Trials. American Journal of Kidney Diseases, [s. l.], v. 71, n. 5, p. 666–676, 2018. DOI 10.1053/j.ajkd.2017.10.023. Disponível em: http://widgets.ebscohost.com/prod/customlink/proxify/proxify.php?count=1&encode=0&proxy=&find_1=&replace_1=&target=http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edselp&AN=S0272638617310971&authtype=sso&custid=s5834912. Acesso em: 5 abr. 2020.
    • AMA:
      Steinman T, Wei J, Czarnecki P, et al. Patterns of Kidney Function Decline in Autosomal Dominant Polycystic Kidney Disease: A Post Hoc Analysis From the HALT-PKD Trials. American Journal of Kidney Diseases. 2018;71(5):666-676. doi:10.1053/j.ajkd.2017.10.023.
    • APA:
      Steinman, T., Wei, J., Czarnecki, P., Pedrosa, I., Braun, W., Nurko, S., Remer, E., Chapman, A., Martin, D., Rahbari-Oskoui, F., Mittal, P., Torres, V., Hogan, M. C., El-Zoghby, Z., Harris, P., Glockner, J., King, J. B., Perrone, R., Halin, N., … Torres, V. E. (2018). Patterns of Kidney Function Decline in Autosomal Dominant Polycystic Kidney Disease: A Post Hoc Analysis From the HALT-PKD Trials. American Journal of Kidney Diseases, 71(5), 666–676. https://doi.org/10.1053/j.ajkd.2017.10.023
    • Chicago/Turabian: Author-Date:
      Steinman, Theodore, Jesse Wei, Peter Czarnecki, Ivan Pedrosa, William Braun, Saul Nurko, Erick Remer, et al. 2018. “Patterns of Kidney Function Decline in Autosomal Dominant Polycystic Kidney Disease: A Post Hoc Analysis From the HALT-PKD Trials.” American Journal of Kidney Diseases 71 (5): 666–76. doi:10.1053/j.ajkd.2017.10.023.
    • Harvard:
      Steinman, T. et al. (2018) ‘Patterns of Kidney Function Decline in Autosomal Dominant Polycystic Kidney Disease: A Post Hoc Analysis From the HALT-PKD Trials’, American Journal of Kidney Diseases, 71(5), pp. 666–676. doi: 10.1053/j.ajkd.2017.10.023.
    • Harvard: Australian:
      Steinman, T, Wei, J, Czarnecki, P, Pedrosa, I, Braun, W, Nurko, S, Remer, E, Chapman, A, Martin, D, Rahbari-Oskoui, F, Mittal, P, Torres, V, Hogan, MC, El-Zoghby, Z, Harris, P, Glockner, J, King, JB, Perrone, R, Halin, N, Miskulin, D, Schrier, R, Brosnahan, G, Gitomer, B, Kelleher, C, Masoumi, A, Patel, N, Winklhofer, F, Grantham, J, Yu, A, Wang, C, Wetzel, L, Moore, CG, Bost, JE, Bae, K, Abebe, KZ, Miller, JP, Thompson, PA, Briggs, J, Flessner, M, Meyers, CM, Star, R, Shayman, J, Henrich, W, Greene, T, Leonard, M, McCullough, P, Moe, S, Rocco, M, Wendler, D, Brosnahan, GM, Abebe, KZ, Moore, CG, Rahbari-Oskoui, FF, Bae, KT, Grantham, JJ, Schrier, RW, Braun, WE, Chapman, AB, Flessner, MF, Harris, PC, Hogan, MC, Perrone, RD, Miskulin, DC, Steinman, TI & Torres, VE 2018, ‘Patterns of Kidney Function Decline in Autosomal Dominant Polycystic Kidney Disease: A Post Hoc Analysis From the HALT-PKD Trials’, American Journal of Kidney Diseases, vol. 71, no. 5, pp. 666–676, viewed 5 April 2020, .
    • MLA:
      Steinman, Theodore, et al. “Patterns of Kidney Function Decline in Autosomal Dominant Polycystic Kidney Disease: A Post Hoc Analysis From the HALT-PKD Trials.” American Journal of Kidney Diseases, vol. 71, no. 5, May 2018, pp. 666–676. EBSCOhost, doi:10.1053/j.ajkd.2017.10.023.
    • Chicago/Turabian: Humanities:
      Steinman, Theodore, Jesse Wei, Peter Czarnecki, Ivan Pedrosa, William Braun, Saul Nurko, Erick Remer, et al. “Patterns of Kidney Function Decline in Autosomal Dominant Polycystic Kidney Disease: A Post Hoc Analysis From the HALT-PKD Trials.” American Journal of Kidney Diseases 71, no. 5 (May 1, 2018): 666–76. doi:10.1053/j.ajkd.2017.10.023.
    • Vancouver/ICMJE:
      Steinman T, Wei J, Czarnecki P, Pedrosa I, Braun W, Nurko S, et al. Patterns of Kidney Function Decline in Autosomal Dominant Polycystic Kidney Disease: A Post Hoc Analysis From the HALT-PKD Trials. American Journal of Kidney Diseases [Internet]. 2018 May 1 [cited 2020 Apr 5];71(5):666–76. Available from: http://widgets.ebscohost.com/prod/customlink/proxify/proxify.php?count=1&encode=0&proxy=&find_1=&replace_1=&target=http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edselp&AN=S0272638617310971&authtype=sso&custid=s5834912