Study of the Link Between Complement Activation and IgA Nephropathy Severity

Study Overview
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Brief Summary
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ICONE study (IgA Complement and NEphropathy is a prospective monocentric observational study. The main objective is to evaluate the relevance of complement activation as a biomarker of disease severity and progression in patients with a biopsy proven IgAN.

Detailed Description
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IgA nephropathy (IgAN) is a common cause of glomerulonephritis and a major cause of end stage renal disease in up to 20-40% of patients. However, its prognosis still cannot be accurately predicted due to the high heterogenicity of clinical presentations and courses. Complement dysregulation is a main driver of glomerular damages in many glomerulonephritis. Given the growing body of evidence of complement lectin/alternative pathways activation in IgAN pathogenesis, the investigators propose the evaluation of a combination of biomarkers of infra-clinical complement activation to stratify the risk of disease's progression. This study aims to identify subsets of patients in whom complement activation plays a critical role in disease progression. This is of particular interest in the aera of emergence of complement-targeting therapies in IgAN

Official Title
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Study of the Link Between Complement Activation and IgA Nephropathy Severity

Conditions
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IgA Nephropathy Severity in Kidney Transplantation

Intervention / Treatment
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* Other: IgAN patients


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, male or female, with a biopsy proven IgA nephropathy. Primitive and secondary forms can be included Regardless of the date of diagnosis and the level of kidney function With or without past of kidney transplantation Followed in the Nephrology Department, Strasbourg University Hospital Signed informed consent Exclusion Criteria: Active or recent infectious or inflammatory syndrome (<2 months), recent vaccination (<2 months), ongoing acute humoral rejection treatment, treatment with plasma exchanges (<2 months), current treatment with complement inhibitors Impossibility of giving informed information (emergency situation, difficulties in understanding, etc.) Subject under safeguard of justice, guardianship or curatorship

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: IgAN patients|Adult patients Histologically proven diagnosis of IgA nephropathy Primary and secondary forms of the disease With or without kidney transplantation history Regardless of kidney/graft function Patients followed in the Nephrology Department of Strasbourg University Hospital.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of a severe form of IgA nephropathy | Occurrence of a severe form of IgA nephropathy, with at least one of the following severity criteria: i) a rapid decline in estimated glomerular filtration rate the incidence of end stage kidney disease, iii) the presence of malignant hypertension or thrombotic microangiopathy features, iv) histological endo and/or extra capillary proliferation (E1 and/or C1 according to Oxford 2016 MEST-C score). Infra-clinical complement activation is defined as a sC5b-9 > 300ng/mL in plasma or a positive ex vivo complement activation functional test on endothelial cells. | At inclusion | 
| Incidence of a severe form of IgA nephropathy | Occurrence of a severe form of IgA nephropathy, with at least one of the following severity criteria: i) a rapid decline in estimated glomerular filtration rate the presence of malignant hypertension or thrombotic microangiopathy features, iv) histological endo and/or extra capillary proliferation (E1 and/or C1 according to Oxford 2016 MEST-C score). | 1 year after inclusion |