French National Cohort MATRIX "Renal and Systemic Thrombotic Microangiopathy"

NCT ID: NCT05991245

Last Updated: 2023-08-14

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 1000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-01-01
• Study Completion Date: 2025-01-31

Brief Summary

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

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).

Conditions

Thrombotic Microangiopathy; Acute Kidney Injury; Hemolytic Uremic Syndrome; Nephrology; Kidney Diseases

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

MATRIX

Thrombotic microangiopathy with kidney biopsy

Collecting datas

Intervention Type: OTHER

Blood, Tissue and Urine samples

Interventions

Collecting datas

Blood, Tissue and Urine samples

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Adult patients 18 years of age or older

2. Who have undergone renal biopsy of the native kidney for impaired renal function between 2009 and July 2022.

3. 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Tours

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean-Michel Halimi, MD, PhD

Role: STUDY_DIRECTOR

CHRU TOURS, Nephrology

Valentin Maisons, MD

Role: PRINCIPAL_INVESTIGATOR

CHRU TOURS, Nephrology

Locations

Department of Nephrology, University Hospital of Tours

Tours, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Jean-Michel Halimi, MD, PhD

Role: CONTACT

jmhalimi@univ-tours.fr

02.47.47.37.46 ext. +33

Valentin Maisons, MD

Role: CONTACT

valentin.maisons@univ-tours.fr

02.47.47.37.46 ext. +33

Facility Contacts

Jean-Michel Halimi, MD,PhD

Role: primary

jmhalimi@univ-tours.fr

02.47.47.37.46 ext. +33

Valentin Maisons, MD

Role: backup

valentin.maisons@univ-tours.fr

02.47.47.37.46 ext. +33

References

Goodship TH, Cook HT, Fakhouri F, Fervenza FC, Fremeaux-Bacchi V, Kavanagh D, Nester CM, Noris M, Pickering MC, Rodriguez de Cordoba S, Roumenina LT, Sethi S, Smith RJ; Conference Participants. Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference. Kidney Int. 2017 Mar;91(3):539-551. doi: 10.1016/j.kint.2016.10.005. Epub 2016 Dec 16.

Reference Type: BACKGROUND

PMID: 27989322 (View on PubMed)

Bayer G, von Tokarski F, Thoreau B, Bauvois A, Barbet C, Cloarec S, Merieau E, Lachot S, Garot D, Bernard L, Gyan E, Perrotin F, Pouplard C, Maillot F, Gatault P, Sautenet B, Rusch E, Buchler M, Vigneau C, Fakhouri F, Halimi JM. Etiology and Outcomes of Thrombotic Microangiopathies. Clin J Am Soc Nephrol. 2019 Apr 5;14(4):557-566. doi: 10.2215/CJN.11470918. Epub 2019 Mar 12.

Reference Type: BACKGROUND

PMID: 30862697 (View on PubMed)

Genest DS, Patriquin CJ, Licht C, John R, Reich HN. Renal Thrombotic Microangiopathy: A Review. Am J Kidney Dis. 2023 May;81(5):591-605. doi: 10.1053/j.ajkd.2022.10.014. Epub 2022 Dec 10.

Reference Type: BACKGROUND

PMID: 36509342 (View on PubMed)

Halimi JM, Duval A, Chardon E, Mesnard L, Frimat M, Fakhouri F, Grange S, Servais A, Cartery C, Coppo P, Titeca-Beauport D, Roger S, Baroukh N, Fage N, Delmas Y, Querard AH, Seret G, Bobot M, Le Quintrec M, Ville S, von Tokarski F, Chauvet S, Wynckel A, Martins M, Schurder J, Barbet C, Sautenet B, Gatault P, Caillard S, Antunes C, Bayer G, Philipponnet C, Audard V, Maillard N, Vuiblet V, Gnemmi V, El Ouafi Z, Canet S, Dekeyser M, Piver E, Maisons V; MATRIX Consortium Group. Diagnostic Value of Biological Parameters in Biopsy-Confirmed Thrombotic Microangiopathy-MATRIX Consortium Group. Kidney Int Rep. 2025 Mar 17;10(6):1950-1959. doi: 10.1016/j.ekir.2025.03.019. eCollection 2025 Jun.

Reference Type: DERIVED

PMID: 40630316 (View on PubMed)

Other Identifiers

F20221110095846

Identifier Type: REGISTRY

Identifier Source: secondary_id

2022-59

Identifier Type: REGISTRY

Identifier Source: secondary_id

RNI/MATRIX

Identifier Type: -

Identifier Source: org_study_id