Glomerular Disease Outcomes Across the Lifespan: Report of the Cure Glomerulonephropathy (CureGN) Research Consortium

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Background: Direct comparisons of outcomes between adult and pediatric patients with primary glomerular disease (GD) are rare. We compared disease outcomes among patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), and IgA nephropathy (IgAN) across the lifespan. Methods: CureGN observational cohort participants enrolled from centers in North America and Europe and followed for at least 1 year were included. With age at biopsy as the primary predictor, we examined risk of death, ESKD, and ≥40% eGFR decline below 60ml/min/1.73m2 stratified by histologic subtype and adjusted for sex, race/ethnicity, proteinuria at biopsy, and eGFR at biopsy in multivariable Cox regression. Results: 2,915 patients (MCD N=647, FSGS N=738, MN N=636, IgA N=894) with a median (IQR) of 5.6y (2.1-7.6) follow-up were included. Pediatric MCD patients had steeper eGFR declines compared to adults (-0.6 to -1.3 mL/min/1.73m2vs. -0.4 to +0.5 mL/min/1.73m2, respectively), while MN patients aged 13-17 and FSGS and IgA patients aged 18-44y at time of biopsy had the steepest declines in eGFR among their diagnosis cohorts. For patients with MCD, FSGS, and MN, no differences were detected among various age groups in the risk of progression to the composite outcome of death, ESKD or ≥40% eGFR decline, while IgA patients aged 6-12y, 13-17y, and 45-64y had lower risks of progression compared to those aged 18-44y (HR [95% CI] 0.33 [0.17-0.62], 0.44 [0.24-0.81], 0.64 [0.43-0.96], respectively). Conclusion: Patients with primary GD face similar risks for declines in kidney function regardless of the age at disease diagnosis. For younger patients, this represents a higher likelihood of reaching ESKD and requiring dialysis and/or transplant in their lifetimes. Funding: NIDDK SupportLeft - eGFR slope by age at biopsy diagnosis and histologic subtype among patients with primary glomerular disease. Right - Hazard ratios for the composite outcome of death, ESKD, or >=40% eGFR decline by age at biopsy diagnosis.

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