French National Cohort MATRIX Renal and Systemic Thrombotic Microangiopathy

Study Overview
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Brief Summary
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Thrombotic microangiopathies (TMAs) are a diverse, rare but serious group of diseases. Progress has been made regarding the epidemiology of TMA (Bayer CJASN 2019). It has been shown that secondary TMAs account for 95% of cases, whereas primary TMAs (atypical hemolytic syndromes (HUS) and thrombotic thrombocytopenic purpura (TTP)) account for only about 5%. However, in many cases, the pathophysiology, optimal management and prognosis of TMA remains unclear and it has been shown that patients with TMA may have renal-limited TMA or renal and hematological TMA (ie. With (mechanical anemia, thrombocytopenia, elevated LDH, decreased haptoglobin, schistocytes). In most studies, kidney biopsies are not performed and the diagnostic workup is uncomplete. As this is a rare disease, only a multicenter approach (>20 centers) over a long period of time (>10 years), with adequate diagnostic workup including kidney biopsies can help us to answer these questions (investigators in the present are usually members of the CNR-MAT (a network of the TMA centers in France).

Detailed Description
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Thrombotic microangiopathies (TMAs) are a diverse, rare but serious group of diseases. Their epidemiology has recently been elucidated thanks to work published by our team. It has been shown that secondary TMAs account for 95% of cases, whereas primary TMAs (atypical hemolytic syndromes (HUS) and thrombotic thrombocytopenic purpura (TTP)) account for only about 5%. However, many epidemiologic problems remain. First, many but not all patients with TMA as classically defined (mechanical anemia, thrombocytopenia, elevated LDH, decreased haptoglobin, schizocytes) have impaired renal function. If a renal biopsy is performed (which is not always the case, as TMA is a risk factor for bleeding after renal biopsy), the renal lesions do not always show renal-limited TMA. We also do not know which of the causes of systemic TMA are associated with renal TMA and which are not. Conversely, in patients with renal biopsy, we can find stigmata of renal-limited TMA in the absence of systemic TMA. Why do some patients have systemic TMA but not renal TMA and others have renal TMA but not systemic TMA? Most studies are based on a few small clinical cases and the literature reviews that report them. The vital, renal, and cardiovascular prognosis of patients with TMA obviously depends on the cause, the clinical presentation of the patients, and their management. However, the renal, systemic, and vital outcomes of renal-only vs. systemic-only vs. systemic and renal TMA, regardless of the cause and severity of TMA, are currently unknown. As this is a rare disease, only a multicenter approach (>20 centers) over a long period of time (>10 years), including highly recruited university and general hospitals, with experienced and motivated investigators, can help us to answer these currently unanswered questions (these investigators usually belong to the competence centers of the national reference center).

Official Title
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French National Cohort MATRIX Renal and Systemic Thrombotic Microangiopathy

Conditions
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Nephrology, Thrombotic Microangiopathy, Acute Kidney Injury, Hemolytic Uremic Syndrome, Kidney Diseases

Intervention / Treatment
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* Other: Collecting datas


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients 18 years of age or older Who have undergone renal biopsy of the native kidney for impaired renal function between 2009 and July 2022. Presence of classically defined systemic MAT (most of the following parameters: elevated LDH, decreased haptoglobin, schizocytes, thrombocytopenia and anemia) AND/OR presence of arteriolar or glomerular renal MAT as indicated by the pathologist (including endothelial turgor, mesangiolysis, double contours, presence of thrombi, fibrinoid necrosis of the arterial wall). Exclusion Criteria: 1. Kidney transplantation

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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| MATRIX<br>Thrombotic microangiopathy with kidney biopsy | Other: Collecting datas<br>* Blood, Tissue and Urine samples<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of isolated renal, hematological or renal associated with hematological features ot thrombotic microangiopathies | Clinical data | 1/ Baseline, ie date of kidney biopsy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess correlations between specific anatomopathological lesions and thrombotic microangiopathies phenotypes | Pathological and clinical data | 1/ Baseline, ie date of kidney biopsy | 
| Assess correlations between cause of thrombotic microangiopathies and clinical phenotypes | Clinical data | 1/ Baseline, ie date of kidney biopsy | 
| Define the biological profile (standard biology and alternative complement pathway analyses including genetic data) of these thrombotic microangiopathies. | Biological data | 1/ Up to 2 weeks after baseline date ; 2/ Date of last follow-up, an average of 2 years | 
| Define the renal, cardiovascular and vital prognosis of these patients | Clinical data | 1/ Hospital discharge date, an average of 2 weeks ; 2/ Date of last follow-up, an average of 2 years | 
| Define treatments for these patients | Clinical data | 1/ Hospital discharge date, an average of 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thrombotic microangiopathy, Acute kidney injury, Hemolytic uremic syndrome, Kidney histology, Complement