Evaluation of Variation in the Performance of GFR Slope as a Surrogate End Point for Kidney Failure in Clinical Trials that Differ by Severity of CKD.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Corporate Authors:
      Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)*
    • Source:
      Publisher: Wolters Kluwer Health Country of Publication: United States NLM ID: 101271570 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1555-905X (Electronic) Linking ISSN: 15559041 NLM ISO Abbreviation: Clin J Am Soc Nephrol Subsets: MEDLINE
    • Publication Information:
      Publication: 2023- : Hagerstown, MD : Wolters Kluwer Health
      Original Publication: Washington, D.C. : American Society of Nephrology, c2005-
    • Subject Terms:
      Renal Insufficiency, Chronic*/diagnosis ; Renal Insufficiency, Chronic*/therapy ; Renal Insufficiency, Chronic*/epidemiology ; Kidney Failure, Chronic* ; Renal Insufficiency*; Humans ; Glomerular Filtration Rate ; Biomarkers ; Disease Progression
    • Abstract:
      Background: The GFR slope has been evaluated as a surrogate end point for kidney failure in meta-analyses on a broad collection of randomized controlled trials (RCTs) in CKD. These analyses evaluate how accurately a treatment effect on GFR slope predicts a treatment effect on kidney failure. We sought to determine whether severity of CKD in the patient population modifies the performance of GFR slope.
      Methods: We performed Bayesian meta-regression analyses on 66 CKD RCTs to evaluate associations between effects on GFR slope (the chronic slope and the total slope over 3 years, expressed as mean differences in ml/min per 1.73 m2/yr) and those of the clinical end point (doubling of serum creatinine, GFR <15 ml/min per 1.73 m2, or kidney failure, expressed as a log-hazard ratio), where models allow interaction with variables defining disease severity. We evaluated three measures (baseline GFR in 10 ml/min per 1.73 m2, baseline urine albumin-to-creatinine ratio [UACR] per doubling in mg/g, and CKD progression rate defined as the control arm chronic slope, in ml/min per 1.73 m2/yr) and defined strong evidence for modification when 95% posterior credible intervals for interaction terms excluded zero.
      Results: There was no evidence for modification by disease severity when evaluating 3-year total slope (95% credible intervals for the interaction slope: baseline GFR [-0.05 to 0.03]; baseline UACR [-0.02 to 0.04]; CKD progression rate [-0.07 to 0.02]). There was strong evidence for modification in evaluations of chronic slope (95% credible intervals: baseline GFR [0.02 to 0.11]; baseline UACR [-0.11 to -0.02]; CKD progression rate [0.01 to 0.15]).
      Conclusions: These analyses indicate consistency of the performance of total slope over 3 years, which provides further evidence for its validity as a surrogate end point in RCTs representing varied CKD populations.
      (Copyright © 2023 by the American Society of Nephrology.)
    • References:
      J Am Soc Nephrol. 2019 Sep;30(9):1735-1745. (PMID: 31292197)
      Ann Intern Med. 2020 Jun 2;172(11):776. (PMID: 32479147)
      Stat Methods Med Res. 2017 Oct;26(5):2287-2318. (PMID: 26271918)
      Kidney Int. 1997 Mar;51(3):793-7. (PMID: 9067912)
      Stat Med. 2019 Sep 30;38(22):4218-4239. (PMID: 31338848)
      J Am Soc Nephrol. 2019 Sep;30(9):1756-1769. (PMID: 31292198)
      Biometrics. 2009 Jun;65(2):530-8. (PMID: 18759836)
      J Am Soc Nephrol. 2022 Feb;33(2):291-303. (PMID: 34862238)
      Stat Med. 2008 Feb 28;27(5):670-86. (PMID: 17492826)
      Stat Med. 2020 Apr 15;39(8):1103-1124. (PMID: 31990083)
      Lancet Diabetes Endocrinol. 2016 Apr;4(4):309-17. (PMID: 26774608)
      Stat Med. 1997 Sep 15;16(17):1965-82. (PMID: 9304767)
      BMJ. 2010 Jun 23;340:c2289. (PMID: 20573762)
      Int J Epidemiol. 2016 Dec 1;45(6):2075-2088. (PMID: 27375287)
      J Am Soc Nephrol. 2009 Apr;20(4):883-92. (PMID: 19225038)
      JAMA Intern Med. 2015 Aug;175(8):1389-98. (PMID: 26098871)
      Ann Intern Med. 2009 May 5;150(9):604-12. (PMID: 19414839)
      Kidney Int. 2013 Sep;84(3):622-3. (PMID: 23989362)
      Ann Intern Med. 1996 Oct 1;125(7):605-13. (PMID: 8815760)
      Am J Kidney Dis. 2014 Dec;64(6):821-35. (PMID: 25441437)
      J Am Soc Nephrol. 2019 Sep;30(9):1746-1755. (PMID: 31292199)
      Kidney Int. 2011 Aug;80(3):282-7. (PMID: 21451458)
    • Grant Information:
      UL1 TR002538 United States TR NCATS NIH HHS
    • Accession Number:
      0 (Biomarkers)
    • Publication Date:
      Date Created: 20230208 Date Completed: 20230210 Latest Revision: 20240306
    • Publication Date:
      20240306
    • Accession Number:
      PMC10103374
    • Accession Number:
      10.2215/CJN.0000000000000050
    • Accession Number:
      36754007