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Abstract: TH-PO0578

Renal Trajectories in the French RaDiCo Alport Syndrome Cohort

Session Information

Category: Genetic Diseases of the Kidneys

  • 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases

Authors

  • Wang, Xiaomeng, Imagine Institute, Necker Hospital, Paris, France
  • Haydock, Ludwig, Necker Hospital, Nephrology Department, APHP, Paris, France
  • Chen, Xiaoyi, Imagine Institute, Necker Hospital, Paris, France
  • Oueslati, Molka, Necker Hospital, Pediatric Nephrology, Paris, France
  • Gueguen, Sonia, Inserm U933, RaDiCo, Hopital Trousseau, Paris, France
  • Heidet, Laurence, Necker Hospital, Pediatric Nephrology, Paris, France
  • Knebelmann, Bertrand, Necker Hospital, Nephrology Department, APHP, Paris, France
Background

Alport syndrome (AS) is increasingly diagnosed due to advances in molecular genetics. While kidney survival by genotypes has been well described, less is known regarding response to RAS inhibition (RASi) and eGFR decline—key factors for future clinical trials

Methods

RaDiCo-Alport is a national, multicenter observational cohort involving 36 nephrology centers. Patients were enrolled from May 2017 to June 2022. Urine protein-to-creatinine ratio (uPCR) before and after initiation of RASi were analyzed at predefined intervals using mixed models for repeated measures (MMRM) on log-transformed values. Individual eGFR slopes (EKFC formula) were estimated by linear regression for chronic kidney disease (CKD) patients with ≥2 measurements and ≥1 year follow-up and then analyzed using univariable linear regressions according to various factors.

Results

641 patients were included: 203 in the male X-linked (MX) group, 179 in the female X-linked (FX) group, 96 in the autosomal dominant (AD) group, 64 in the autosomal recessive (AR) group, and 99 with uncertain inheritance. Among them, 303 patients received RASi treatment. The estimated mean uPCR values (mg/mmol, 95% CI) at each treatment interval were: M0 - 88 (75, 103), M12 - 61 (52, 73), M24 - 57 (48, 69), M36 - 58 (49, 69), M60 - 75 (64, 88), M84 - 78 (64, 94), M120 - 64 (46, 88). These results indicate significant uPCR reduction up to M36, followed by an escape from efficacy. The median eGFR slope was -2.4 (-4.4, -0.5) ml/min/1.73m2/year. Faster decline was observed in the AD and AR+MX groups compared to the FX group. Baseline uPCR (from 100 mg/mmol) significantly impacted progression (Figure1)

Conclusion

The RaDiCo-Alport cohort provides valuable insights into the natural history of AS and will help refine selection criteria and efficacy endpoints for clinical trials.

Factors associated with individual eGFR slopes (univariable linear regression)

Funding

  • Government Support – Non-U.S.

Digital Object Identifier (DOI)