NKF-FDA-EMA Workshop

The National Kidney Foundation is collaborating with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to host a scientific workshop to evaluate alternative endpoints for clinical trials in the early stages of CKD. An integral part of the initiative, now underway, is an extensive meta-analysis of existing data from both interventional clinical trials and observational cohort data to evaluate changes in albuminuria (or proteinuria), the rate of GFR decline, and combinations of both strategies, as predictors of kidney disease progression, kidney failure and other adverse clinical outcomes.

The analysis and conference will expand on prior studies of albuminuria as a surrogate endpoint, and address outstanding questions about the use of albuminuria as a surrogate endpoint, particularly in early stages of CKD.1-7 In addition, the analysis and conference will build on the 2012 NKF-FDA Workshop, "GFR Decline as an End Point in Clinical Trials in CKD" that showed strong relationships between change in eGFR and kidney failure and mortality in observational studies and in past clinical trials.8-12 Finally, the conference will explore how combinations of these endpoints might be useful, in clinical practice as well as clinical trials.

Following the workshop, to be held in the Washington, DC area on March 15-16, 2018, there will be a series of publications reporting on the workshop deliberations and the results of pre-workshop data analyses and trial simulations being conducted by investigators at Johns Hopkins University, Tufts University, the University of Utah, and Groningen University.

WORKSHOP DOCUMENTS CAN BE ACCESSED HERE (Password protected)

If you want further information about this initiative, please contact Tom Manley.

References:

  1. Fried LF, Lewis J. Rebuttal of the Pro View: Albuminuria Is an Appropriate Therapeutic Target in Patients with CKD. Clin J Am Soc Nephrol. Jun 05 2015;10(6):1095-1098.
  2. Fried LF, Lewis J. Albuminuria is Not an Appropriate Therapeutic Target in Patients with CKD: The Con View. Clin J Am Soc Nephrol. Jun 05 2015;10(6):1089-1093.
  3. Heerspink HJ, Kropelin TF, Hoekman J, de Zeeuw D. Drug-Induced Reduction in Albuminuria Is Associated with Subsequent Renoprotection: A Meta-Analysis. J Am Soc Nephrol. Aug 2015;26(8):2055-2064.
  4. Inker LA, Levey AS, Pandya K, Stoycheff N, Okparavero A, Greene T. Early change in proteinuria as a surrogate end point for kidney disease progression: an individual patient meta-analysis. Am J Kidney Dis. Jul 2014;64(1):74-85.
  5. Lambers Heerspink HJ, Gansevoort RT. Rebuttal of the Con View: Albuminuria Is an Appropriate Therapeutic Target in Patients with CKD. Clin J Am Soc Nephrol. Jun 05 2015;10(6):1099.
  6. Lambers Heerspink HJ, Gansevoort RT. Albuminuria Is an Appropriate Therapeutic Target in Patients with CKD: The Pro View. Clin J Am Soc Nephrol. Jun 05 2015;10(6):1079-1088.
  7. Levey AS, Cattran D, Friedman A, et al. Proteinuria as a surrogate outcome in CKD: report of a scientific workshop sponsored by the National Kidney Foundation and the US Food and Drug Administration. Am J Kidney Dis. Aug 2009;54(2):205-226.
  8. Coresh J, Turin TC, Matsushita K, et al. Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality. Jama. Jun 25 2014;311(24):2518-2531.
  9. Greene T, Teng CC, Inker LA, et al. Utility and validity of estimated GFR-based surrogate time-to-event end points in CKD: a simulation study. Am J Kidney Dis. Dec 2014;64(6):867-879.
  10. Inker LA, Lambers Heerspink HJ, Mondal H, et al. GFR decline as an alternative end point to kidney failure in clinical trials: a meta-analysis of treatment effects from 37 randomized trials. Am J Kidney Dis. Dec 2014;64(6):848-859.
  11. Lambers Heerspink HJ, Tighiouart H, Sang Y, et al. GFR decline and subsequent risk of established kidney outcomes: a meta-analysis of 37 randomized controlled trials. Am J Kidney Dis. Dec 2014;64(6):860-866.
  12. Levey AS, Inker LA, Matsushita K, et al. GFR decline as an end point for clinical trials in CKD: a scientific workshop sponsored by the National Kidney Foundation and the US Food and Drug Administration. Am J Kidney Dis. Dec 2014;64(6):821-835.