Journal article
Results from a national-wide retrospective cohort measure the impact of C3 and soluble C5b-9 levels on kidney outcomes in C3 glomerulopathy
Kidney international, Vol.102(4), pp.904-916
06/22/2022
DOI: 10.1016/j.kint.2022.05.027
PMCID: PMC10588728
PMID: 35752323
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.
Details
- Title: Subtitle
- Results from a national-wide retrospective cohort measure the impact of C3 and soluble C5b-9 levels on kidney outcomes in C3 glomerulopathy
- Creators
- Sophie Chauvet - Hôpital Européen Georges-PompidouJill J Hauer - University of IowaFlorent Petitprez - La Ligue Contre le CancerMarion Rabant - Hôpital Necker-Enfants MaladesPaula Vieira Martins - Hôpital EuropéenVéronique Baudouin - Hôpital Robert-DebréYahsou Delmas - Department of nephrology, CH Bordeaux, France.Noémie Jourde-Chiche - department of Nephrology, CHU Marseille.Alexandre Cez - Aix-Marseille UniversitéDavid Ribes - department of Nephrology, CHU Toulouse, France.Sylvie Cloarec - Centre Hospitalier Universitaire de ToursAude Servais - Hôpital Necker-Enfants MaladesMohamad Zaidan - Bicêtre HospitalEric Daugas - Assistance Publique – Hôpitaux de ParisMichel Delahousse - Hôpital FochAlain Wynckel - department of Nephrology, CHU Reims, France.Amélie Ryckewaert - Department of VirologyAnne Laure Sellier-Leclerc - Department of pediatric nephrology, CHU Lyon France.Olivia Boyer - Hôpital Necker-Enfants MaladesEric Thervet - Hôpital EuropéenAlexandre Karras - Hôpital EuropéenRichard J H Smith - University of IowaVéronique Frémeaux-Bacchi - Hôpital Européen
- Resource Type
- Journal article
- Publication Details
- Kidney international, Vol.102(4), pp.904-916
- DOI
- 10.1016/j.kint.2022.05.027
- PMID
- 35752323
- PMCID
- PMC10588728
- NLM abbreviation
- Kidney Int
- ISSN
- 0085-2538
- eISSN
- 1523-1755
- Language
- English
- Date published
- 06/22/2022
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
- Record Identifier
- 9984269211402771
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