Kidney Week

Abstract: SA-PO0572

Comparison of Surrogate Kidney End Points for Clinical Trials in PKD

Session Information

• Cystic Kidney Diseases: Clinical Research
  November 08, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases

Authors

• Noruzi, Anahita, Erasmus MC, Rotterdam, ZH, Netherlands

Anahita Noruzi, MD, MSc

• Bais, Thomas, Universitair Medisch Centrum Groningen, Groningen, GR, Netherlands

Thomas Bais, MD

• Xue, Laixi, Erasmus MC, Rotterdam, ZH, Netherlands

Laixi Xue, MD

• Meijer, Esther, Universitair Medisch Centrum Groningen, Groningen, GR, Netherlands

Esther Meijer, MD, PhD

• van Gastel, Maatje D.A., Universitair Medisch Centrum Groningen, Groningen, GR, Netherlands

Maatje D.A. van Gastel

• Drenth, Joost P.H., Radboud universitair medisch centrum, Nijmegen, GE, Netherlands

Joost P.H. Drenth, MD, PhD

• Spijker, Siebe, Leids Universitair Medisch Centrum, Leiden, ZH, Netherlands

Siebe Spijker, MD, PhD

• Nijenhuis, Tom, Radboud universitair medisch centrum, Nijmegen, GE, Netherlands

Tom Nijenhuis, MD, PhD

• Peters, Dorien J.M., Leids Universitair Medisch Centrum, Leiden, ZH, Netherlands

Dorien J.M. Peters, PhD

• Hoorn, Ewout J., Erasmus MC, Rotterdam, ZH, Netherlands

Ewout J. Hoorn, MD, PhD

• Salih, Mahdi, Erasmus MC, Rotterdam, ZH, Netherlands

Mahdi Salih, MD, PhD

• Gansevoort, Ron T., Universitair Medisch Centrum Groningen, Groningen, GR, Netherlands

Ron T. Gansevoort, MD, PhD, FASN

Group or Team Name

• On behalf of the DIPAK Consortium.

Background

Autosomal dominant polycystic kidney disease (ADPKD) progresses at highly variable rates. The introduction of new medications necessitates further studies and highlights the importance of identifying meaningful renal outcomes. In nephrology, the classical endpoint for clinical trials has been an eGFR decline ≥57% from baseline, or initiation of kidney replacement therapy (KRT). We studied whether using lesser declines in eGFR or a difference in eGFR slope also captures patients with rapid disease progression and improves power to detect meaningful differences.

Methods

We analyzed data from the DIPAK cohort, a Dutch prospective multicenter observational study, with an average follow-up of 5.1 years. We studied characteristics of patients who reached eGFR decline thresholds of ≥20%, ≥30% and ≥40% or KRT from baseline, and compared them with those who reached ≥57% or KRT. Multivariable models identified factors associated with each threshold. In patients typically included in trials (age <55 years, eGFR ≥30 ml/min/1.73m², Mayo class 1C/D/E), we performed sample size simulations, to assess the implications of different thresholds for clinical trial design.

Results

Among 590 patients (mean age 48 ± 12 years, eGFR 64 ± 29 mL/min/1.73m2), 333, 242, 178 and 117 reached a ≥20%, ≥30%, ≥40%, and ≥57% or initiated KRT, respectively. Higher thresholds (≥40% and ≥57%) captured patients with more advanced disease, as reflected by lower baseline eGFR and larger total kidney volumes. Mean annual eGFR declines were -4.2, -4.5, -4.7, and -5.1 mL/min/1.73m2, respectively. Independent predictors of eGFR decline included lower baseline eGFR, higher blood pressure, male sex, and PKD1 truncating variants. Sample size simulations indicated that using lower eGFR decline thresholds necessitates fewer patients to be included, yet still require more patients than slope-based endpoints.

Conclusion

Using ≥20-30% eGFR decline identifies patients with rapid disease progression, at earlier stages of the disease. Using eGFR thresholds requires larger numbers of trial-eligible patients, supporting the use of eGFR slope as a more efficient trial endpoint.

Funding

• Government Support – Non-U.S.

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025atsty8gb