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Kidney Week

Abstract: SA-PO948

Rate of Loss of eGFR and Time-Averaged Proteinuria in IgA Nephropathy (IgAN) Patients Progressing from Early-Stage Disease to Kidney Failure

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Pitcher, David, UK Renal Registry, Bristol, United Kingdom
  • Braddon, Fiona E. M., UK Renal Registry, Bristol, United Kingdom
  • Hendry, Bruce M., Travere Therapeutics Inc, San Diego, California, United States
  • Mercer, Alex, JAMCO Pharma Consulting, Stockholm, Sweden
  • Osmaston, Kate, UK Renal Registry, Bristol, United Kingdom
  • Saleem, Moin, University of Bristol & Bristol Royal Hospital for Children, Bristol, United Kingdom
  • Steenkamp, Retha D., UK Renal Registry, Bristol, United Kingdom
  • Gong, Wu, Travere Therapeutics Inc, San Diego, California, United States
  • Turner, A. Neil, University of Edinburgh, Edinburgh, United Kingdom
  • Barratt, Jonathan, University of Leicester & Leicester General Hospital, Leicester, United Kingdom
  • Gale, Daniel P., Royal Free Hospital & University College London, London, United Kingdom
Background

Cohort studies in IgAN have analyzed time-averaged proteinuria (TA-PU) and eGFR decline over long-term follow-up (f/u), and randomized controlled trials typically measure proteinuria and eGFR over 1-2 years, but none compare disease progression in early vs later stages of disease. In this study of patients enrolled into the UK National Registry of Rare Kidney Diseases (RaDaR) with biopsy-proven IgAN and f/u data spanning early-to-late CKD stages, we present preliminary findings comparing the extent of proteinuria (PU) and eGFR decline prior to and after entering CKD stage 3B.

Methods

Linear regression of eGFR values from baseline (first PU value ≥6mo after diagnosis) until kidney replacement therapy initiation or end of f/u was used to define patient’s Time0 as the estimated date their eGFR passed 45. Longitudinal PU was assessed as TA-PU. Differences in eGFR slope and TA-PU before and after Time0 were analyzed using multilevel models and paired t-test; patients were required to have ≥3 eGFR and ≥2 PU values before and after Time0.

Results

eGFR decline was rapid and comparable in the 2 periods, either unadjusted or adjusted for age and sex (Table 1A; Figure). TA-PU was 41.4% greater in patients after progressing through the 45 ml/min/1.73m2 threshold than before reaching this mark (Table 1B).

Conclusion

Given the comparability of eGFR decline prior to and after passing an eGFR of 45ml/min/1.73m2, slope measurements in early disease stages may be useful in estimating future eGFR loss. Comparability of eGFR slopes but differences in TA-PU suggest patients with stable rates of eGFR loss suffer increasing damage to the glomerular filtration barrier.

Funding

  • Commercial Support – Travere Therapeutics, Inc.