Logo image
Back
Renal pathology as a predictor of complement dysregulation in C3 glomerulopathy
Abstract   Open access   Peer reviewed

Renal pathology as a predictor of complement dysregulation in C3 glomerulopathy

Jillian Hall, Lauren Fergus, Tina Liu, Monica Hall, Patrick Walker, Richard Smith and Carla Nester
Immunobiology (1979), Vol.230(4), p.153017
07/2025
DOI: 10.1016/j.imbio.2025.153017
url
https://doi.org/10.1016/j.imbio.2025.153017View
Published (Version of record) Open Access

Abstract

C3 Glomerulopathy (C3G) is characterized by complement dysregulation and resulting C3 deposition in glomeruli. We reviewed the characteristics of the baseline kidney biopsy in a cohort of patients with C3G to determine whether biopsy features of activity and chronicity at presentation correlate with complement dysregulation across the disease course. Patient data from the University of Iowa’s C3G Natural History Study were used. Criteria for entry included baseline native biopsy diagnosis of C3G, complement biomarkers within 1 year of diagnostic biopsy, and at least one additional complement panel drawn greater than one year later. Patients with a history of dialysis, transplant, or anti-complement therapy were excluded. Significance was assessed using Pearson correlation coefficients with two-tailed p values (95% confidence); results were considered statistically significant when p-values were less than 0.05. Of 59 subjects, 35 (59.3%) presented with an activity score of ≥9 while 12 (20.3%) presented with a chronicity score of ≥4, the a priori determinants of increased risk for progression to renal failure. A high activity score was associated with a high soluble C5b-9 (p = 0.009) and a negative slope over time (p = 0.042, R = −0.283). In patients >18 years of age, a high activity score was also associated with an increased Ba slope over time (p = 0.03, R = 0.579). In patients who presented <12 years of age, the index chronicity score correlated with a sustained increase of C5 nephritic factor (p = 0.023, R = 0.532). Some complement biomarkers correlate with indices of renal pathology in C3G. Specifically, a more severe activity score correlates with a high soluble C5b-9 and a progressive increase in Ba, consistent with complement activity playing a role in renal inflammation. The relationship between an increased chronicity score and sustained elevation of C5 nephritic factor in the pediatric population points to a longer-term effect of ongoing terminal pathway activity. Kidney Int. 2018 Apr;93(4):977–985, Clin J Am Soc Nephrol. 2022 Jul;17(7):994–1007, Am J Kidney Dis. 2021 May;77(5):684–695.e1. NIDDK: R01 110023.

Details

Metrics

20 Record Views
Logo image