Results from a nationwide retrospective cohort measure the impact of C3 and soluble C5b-9 levels on kidney outcomes in C3 glomerulopathy.

Abstract

C3 glomerulopathy (C3G) is a rare complement-mediated disease. Specific treatments are not yet available and factors predictive of kidney survival such as age, kidney function and proteinuria are not specific to C3G. The prognostic value of biomarkers of complement activation, which are pathognomonic of the diseases, remains unknown. In a large cohort of 165 patients from the French National registry, we retrospectively assess the prognostic value of C3, soluble C5b-9 (sC5b-9), C3 nephritic factor, and rare disease-predicting variants in complement genes in predicting clinical outcome of patients. By multivariate analysis age (adult onset), reduced kidney function (defined by estimated glomerular filtration rate under 60ml/min) and presence of rare disease-predicting variants in complement genes predicted risk of progression to kidney failure. Moreover, by multivariate analysis, normal C3/high sC5b-9 levels or low C3/normal sC5b-9 levels remained independently associated with a worse kidney prognosis, with the relative risk 3.7- and 8-times higher, respectively. Subgroup analysis indicated that the complement biomarker profiles independently correlated to kidney prognosis in patients with adult but not pediatric onset. In this subgroup, we showed that profiles of biomarkers C3 and/or sC5b-9 correlated with intra glomerular inflammation and may explain kidney outcomes. In children, only the presence of rare disease-predicting variants correlated with kidney survival. Thus, in an adult population, we propose a three-point C3G prognostic score based on biomarker profiles at risk, estimated glomerular filtration rate at presentation and genetic findings, which may help stratify adult patients into subgroups that require close monitoring and more aggressive therapy.

• Authors: Sophie Chauvet, Jill J Hauer, Florent Petitprez, Marion Rabant, Paula Vieira Martins, Véronique Baudouin, Yahsou Delmas, Noémie Jourde-Chiche, Alexandre Cez, David Ribes, Sylvie Cloarec, Aude Servais, Mohamad Zaidan, Eric Daugas, Michel Delahousse, Alain Wynckel, Amélie Ryckewaert, Anne Laure Sellier-Leclerc, Olivia Boyer, Eric Thervet, Alexandre Karras, Richard J H Smith, Véronique Frémeaux-Bacchi
• Journal: Kidney international (Kidney Int) Vol. 102 Issue 4 Pg. 904-916 (10 2022) ISSN: 1523-1755 [Electronic] United States
• PMID: 35752323 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• Complement C3
• Complement C3 Nephritic Factor
• Complement Membrane Attack Complex

Topics

• Adult
• Biomarkers
• Child
• Complement C3 (genetics)
• Complement C3 Nephritic Factor (genetics)
• Complement Membrane Attack Complex
• Glomerulonephritis, Membranoproliferative (drug therapy, genetics)
• Humans
• Kidney Diseases (diagnosis, genetics)
• Kidney Glomerulus
• Rare Diseases
• Retrospective Studies