Kidney Week

Abstract: TH-OR069

Proteinuria and Short-Term eGFR Decline in FSGS

Session Information

• Glomerular Diseases: Epidemiology and Real-World Outcomes
  October 22, 2026 | Location: Room 501, Convention Center
  Abstract Time: 05:20 PM - 05:30 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Smith, Abigail R., Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Abigail R. Smith, PhD

• Helmuth, Margaret, University of Michigan, Ann Arbor, Michigan, United States

Margaret Helmuth, MA

• Derebail, Vimal K., The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States

Vimal K. Derebail, MD, MPH, FASN

• Angeletti, Andrea, Istituto Giannina Gaslini, Genoa, Liguria, Italy

Andrea Angeletti, MD, PhD

• Schaefer, Franz, Universitat Heidelberg, Heidelberg, BW, Germany

Franz Schaefer, MD, PhD

• Caravaca-Fontan, Fernando, Hospital Universitario 12 de Octubre, Madrid, Community of Madrid, Spain

Fernando Caravaca-Fontan, MD, PhD

• Jauhal, Arenn Singh, University of Toronto, Toronto, Ontario, Canada

Arenn Singh Jauhal, MD, MS, MSc

• Khalid, Myda, Indiana University School of Medicine, Indianapolis, Indiana, United States

Myda Khalid, MD, FASN

• Modi, Zubin J., University of Michigan, Ann Arbor, Michigan, United States

Zubin J. Modi, MD, MS

• Damashek, Laurel J., International Society of Glomerular Disease, Florence, Massachusetts, United States

Laurel J. Damashek, MA

• Kretzler, Matthias, University of Michigan, Ann Arbor, Michigan, United States

Matthias Kretzler, MD

• Mariani, Laura H., University of Michigan, Ann Arbor, Michigan, United States

Laura H. Mariani, MD, MS, FASN

Group or Team Name

• the PARASOL consortium

Background

Prior work in PARASOL has demonstrated challenges with eGFR as a clinical trial outcome in FSGS, largely due to variability within and across patients. While continuous endpoints like eGFR slope are more statistically efficient, high variability could make trials infeasible to due sample size requirements. Our objective was to assess eGFR percent decline endpoints to inform performance in clinical trials.

Methods

Datasets from 9 registries across North America and Europe were harmonized. Eligible participants had biopsy-proven or genetic FSGS, UPCR≥1.5 g/g at index with associated eGFR≥30 ml/min/1.73m², at least one UPCR up to 1yr, and at least 2yrs of follow-up post-index. eGFR decline was defined as sustained 30 and 40% below index with eGFR<90 ml/min/1.73m² within 2yrs. Associations with proteinuria response<0.3-1.0 g/g were assessed using multivariable logistic regression and interactions were tested to identify differences by subgroup.

Results

1533 participants were included; median age was 21 (IQR 9-43), 46% were pediatric, 54% were male. Median (IQR) UPCR and eGFR at index were 3.8 (2.3, 7.1) g/g and 82 (56, 110) ml/min/1.73m², respectively. At index, 53% had UPCR≥3.5 g/g and 30% were CKD stage 3 or higher. 2-yr eGFR decline≥30% and 40% occurred in 19% and 13% of participants, respectively. Odds of eGFR decline were higher in pediatrics (aOR₃₀=1.4, 95% CI = 1.1-1.8; aOR₄₀=1.4, 95% CI = 1.0-1.9), those with UPCR≥3.5 g/g at index (aOR₃₀=1.6, 95% CI = 1.3-2.1; aOR₄₀=1.8, 95% CI = 1.3-2.5), and those in CKD stage 3 or higher at index (aOR₃₀=1.7, 95% CI = 1.3-2.3; aOR₄₀=1.7, 95% CI = 1.2-2.4). Those achieving UPCR<0.3-<1.0 g/g by 1yr had lower odds of 30% and 40% eGFR decline over 2 years (aOR₃₀ range 0.26-0.30; aOR₄₀ range 0.15-0.22, Figure). No differences in associations by subgroups defined by age, index UPCR or eGFR were detected.

Conclusion

Achievement of proteinuria reduction down to thresholds as high as 1.0 g/g at 1yr was associated with substantial reduction in the odds of sustained 30 or 40% eGFR decline by 2yrs. This observed association may indicate that % decline in eGFR could be useful in understanding the clinical benefit of proteinuria reduction.

Funding

• Private Foundation Support