Kidney Week

Abstract: SA-PO803

C3 Nephrotic Factor at Diagnosis Is Associated with Better eGFR Preservation in Patients with C3 Glomerulopathy (C3G): Findings from the European Rare Kidney Disease Registry (ERKReg)

Session Information

• C3G, TMA, MGRS, Amyloidosis, and More
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Hofstetter, Jonas, European Rare Kidney Disease Reference Network, Heidelberg, Baden-Württemberg, Germany

Jonas Hofstetter, MSc

• Vivarelli, Marina, Ospedale Pediatrico Bambino Gesu, Roma, Italy

Marina Vivarelli, MD

• Perez-Beltran, Victor, Hospital Universitari Vall d'Hebron, Barcelona, Catalunya, Spain

Victor Perez-Beltran, MD

• Conlon, Peter J., Beaumont Hospital, Dublin, Dublin, Ireland

Peter J. Conlon, MD, MBBS, MBChB

• Vidal, Enrico, Azienda Ospedale Universita Padova, Padova, Veneto, Italy

Enrico Vidal, MD, PhD

• Schaefer, Franz, European Rare Kidney Disease Reference Network, Heidelberg, Baden-Württemberg, Germany

Franz Schaefer, MD, PhD

Background

C3G and ic-MPGN are complement-mediated rare kidney disorders with variable responsiveness to standard immunosuppressive protocols. Information regarding biomarkers of therapeutic responsiveness is scarce. ERKReg, a longitudinal pan-European registry for rare kidney diseases is currently following >9,000 patients with rare glomerulopathies, including 484 patients with C3G/ic-MPGN. We assessed the database for risk factors associated with a progressive disease course.

Methods

Retrospective diagnostic and prospective follow-up information was extracted from a total of 208 C3G/ic-MPGN patients enrolled in ERKReg between 10/2018 and 05/2024, most commonly (84%) as prevalent patients with a median (IQR) total disease duration of 5.8 (2.9; 9.3) years. Serum C3NeF at time of diagnosis was available for 55 C3G patients (cohort 1) and serum C3 for 146 C3G and 62 ic-MPGN patients (cohort 2). Multivariable, linear mixed-effects models were fitted to longitudinal eGFR adjusted for sex, eGFR and age at first visit (baseline), hypertension and RASi therapy for each cohort to investigate whether C3NeF status and/or serum C3 levels at diagnosis were associated with prospective eGFR change.

Results

Disease onset was observed at childhood age in 77%. Prospective observation time accounted for a median of 21% (0%; 52%) of total disease duration. eGFR at baseline was 103 (66;127) ml/min/1.73m². Systolic hypertension was documented in 21% and RASi therapy in 69% of visits.
In cohort 1, eGFR improved with time in C3G patients positive for C3NeF at diagnosis (ß=1.1, p =0.039) whereas C3NeF-negative patients exhibited a negative eGFR slope (ß=-3.9, p <0.01). In cohort 2, low vs. normal C3 levels at time of diagnosis tended to associate with improved eGFR preservation (ß^Δ=2.69, p = 0.078). Among the potential confounder variables accounted for in the models, adult age at baseline had a distinct negative association with eGFR over time in both cohorts.

Conclusion

In patients with C3G undergoing standard-of-care management in the past 5 years, the detection of C3NeF at time of diagnosis was associated with better kidney function. We speculate that C3NeF identifies a subset of patients with greater sensitivity to standard immunosuppressive therapies.

Funding

• Commercial Support – Novartis