Long-Term Outcomes of C3 Glomerulopathy and Immune-Complex Membranoproliferative Glomerulonephritis in Children

Amrit Kirpalani; Natasha Jawa; William E Smoyer; Christoph Licht; Midwest Pediatric Nephrology Consortium

doi:10.1016/j.ekir.2020.09.019

Long-Term Outcomes of C3 Glomerulopathy and Immune-Complex Membranoproliferative Glomerulonephritis in Children

Kidney Int Rep. 2020 Oct 3;5(12):2313-2324. doi: 10.1016/j.ekir.2020.09.019. eCollection 2020 Dec.

Authors

Amrit Kirpalani^{1

2}, Natasha Jawa¹, William E Smoyer^{3

4}, Christoph Licht^{1

2

5

6

7}; Midwest Pediatric Nephrology Consortium

Collaborators

Midwest Pediatric Nephrology Consortium:
Gina-Marie Barletta, Sharon Bartosh, Neal Blatt, Tom Blydt-Hansen, Patrick Brophy, Lawrence Copelovitch, Brad Dixon, Anne Durkan, Matthew Eison, Larry Greenbaum, Guillermo Hidalgo, Deborah Jones, Mini Michael, John Sanders, Donald Weaver, Amy Wilson

Affiliations

¹ Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada.
² Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.
³ The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
⁴ Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA.
⁵ Cell Biology Program, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
⁶ Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
⁷ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.

Abstract

Introduction: The reclassification of membranoproliferative glomerulonephritis (MPGN) into immune-complex MPGN (IC-MPGN) and C3 glomerulopathy (C3G) has provided insights into 2 distinct diseases. Although outcomes in adults are poor in both diseases, the pediatric literature is scarce and limited to small, single-center cohorts.

Methods: We conducted a retrospective analysis of 165 pediatric patients across 17 hospitals to compare outcomes between children with IC-MPGN and C3G.

Results: Forty-two percent of patients initially diagnosed with MPGN were reclassified as C3G after a review of renal biopsy reports. There was a trend toward higher serum creatinine levels in patients with C3G compared with IC-MPGN both at diagnosis (mean 168.9 [range 45.4-292.4] vs. 93.7 [range 70.7-116.6] μmol/l, P = 0.25) and after a mean follow-up time of 4 years (mean 145.0 (range -8.1 to 298.1) vs 99.1 (range 46.3-151.9) μmol/l, P = 0.47), although the estimated glomerular filtration rate (eGFR) was not significantly different. Steroid treatment was associated with a significant improvement in eGFR versus no steroids in C3G (mean +43.0 (range 12.9-73.0) vs. -3.0 (range -23.1 to 17.2) ml/min per 1.73 m², P = 0.02) but not in IC-MPGN. Overall kidney function was preserved in both groups although hypertension remained prevalent in 42.5% of the cohort at the last follow-up, and the urine protein/creatinine ratio remained elevated (mean 253.8 [range 91.9-415.7] mg/mmol).

Conclusion: This large pediatric IC-MPGN/C3G cohort revealed nearly half of the patients were misclassified, and there may be a trend toward worse renal prognosis in C3G although they may have greater steroid responsiveness. The overall prognosis appears to be more favorable than in adults; however, persistent hypertension and proteinuria suggest suboptimal disease control.

Keywords: C3 glomerulonephritis; C3 glomerulopathy; dense deposit disease; hypertension; immune-complex membranoproliferative glomerulonephritis; proteinuria.