Kidney Week

Abstract: TH-PO586

Patterns of Disease Progression Among Children and Adults with IgA Nephropathy/Vasculitis in CureGN

Session Information

• Glomerular Diseases: Clinical and Epidemiologic Studies
  November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

• Glenn, Dorey A., The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States

Dorey A. Glenn,

• Carver, Ashley W., The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States

Ashley W. Carver,

• Helmuth, Margaret, Arbor Research Collaborative for Health, Ann Arbor, Michigan, United States

Margaret Helmuth,

• Smith, Abigail R., Arbor Research Collaborative for Health, Ann Arbor, Michigan, United States

Abigail R. Smith,

• Canetta, Pietro A., Columbia University, New York, New York, United States

Pietro A. Canetta,

• Nast, Cynthia C., Cedars-Sinai Medical Center, Los Angeles, California, United States

Cynthia C. Nast,

• Reich, Heather N., Toronto General Research Institute, Toronto, Ontario, Canada

Heather N. Reich,

• Nester, Carla Marie, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States

Carla Marie Nester,

• Khalid, Myda, Riley Hospital for Children at Indiana University Health, Indianapolis, Indiana, United States

Myda Khalid,

Group or Team Name

• On Behalf of the CureGN IgA Working Group.

Background

IgA nephropathy (IgAN) is the most common glomerular disease world-wide. Identifying demographic and clinical characteristics that place patients at increased risk for disease progression is critical for optimizing therapeutic interventions and targeting clinical trials.

Methods

CureGN is a multi-center cohort study of children and adults with biopsy-proven glomerular disease, including 823 patients with IgA nephropathy/vasculitis with nephritis (IgAN/IgAVN). We used latent class analysis to segregate 316 incident and prevalent patients, with at least 4 UPCR measurements within the first 2 years of their follow-up, into 3 groups based on longitudinal UPCR trajectories over 2 years. Using Cox proportional hazard models, we then modeled disease progression, defined as the composite outcome of 40% eGFR decline or kidney failure (initiation of dialysis, transplant, or 2 eGFRs <15ml/min/1.73m²), as a function of UPCR trajectory group while adjusting for age, eGFR at enrollment, use of immunosuppression, RAAS blockade, and IgAN/IgAVN status.

Results

149 incident and 167 prevalent patients (enrolled <6 months and > 6 months from biopsy (max 5 years), respectively) were followed for a median of 6.1 (IQR 4.5,6.9) years. Three groups were identified based on UPCR trajectories (Figure). Among incident patients, those with the highest UPCR (group 3) demonstrated faster eGFR decline (median (IQR) decline -4.0 (-7.3,-0.1) ml/min/1.73m²/year compared to +1.3 (-2.0,+3.1) in group 1 and -0.9 (-3.9,+1.7) in group 2) and had 5.4-times higher hazard of progressing to the composite outcome compared to Groups 1+2 combined (p=0.0016). Among prevalent patients, those with the highest UPCR (Group 3) had 3.9-times higher hazard of progressing to the composite outcome (p=0.0049). No association between immunosuppression use and the composite outcome was detected.

Conclusion

In both incident and prevalent IgAN/IgAVN cohorts proteinuria trajectories define patients into distinct clinical groups and are a strong independent predictor of disease progression.

Funding

• NIDDK Support