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RecruitingNCT05991245MATRIXUpdated Aug 14, 2023

French National Cohort MATRIX "Renal and Systemic Thrombotic Microangiopathy"

An observational study in Thrombotic Microangiopathy, Acute Kidney Injury and Hemolytic Uremic Syndrome, sponsored by University Hospital, Tours. Recruiting at 1 site in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-08-14.

Sponsored by University Hospital, Tours · Observational

Study type
Observational
Model
Cohort
Time perspective
Retrospective
Enrollment
1,000
Ages
18 Years and older
Sex
All
01

Study 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).

Read the 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).

02

Conditions studied

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

Keywords

  • Thrombotic microangiopathy
  • Acute kidney injury
  • Hemolytic uremic syndrome
  • Kidney histology
  • Complement
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No
Sampling method
Non-probability sample

Study population

The population corresponds to French adult nephrology patients with renal and/or systemic thrombotic microangiopathy, for whom renal biopsy data are available. It is not extendable to renal transplant patients.

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

Exclusion Criteria:

  1. Kidney transplantation
04

Study design

Observational model
Cohort
Time perspective
Retrospective
Enrollment
1,000 participants (estimated)
Patient registry
No
Biospecimen retention
Samples with dna

Groups and cohorts

  • MATRIX

    Thrombotic microangiopathy with kidney biopsy

    Other: Collecting datas

Interventions

  • OtherCollecting datas

    Blood, Tissue and Urine samples

05

What researchers measure

Primary outcomes

  1. Presence of isolated renal, hematological or renal associated with hematological features ot thrombotic microangiopathies

    Clinical data

    Time frame: 1/ Baseline, ie date of kidney biopsy

Secondary outcomes

  1. Assess correlations between specific anatomopathological lesions and thrombotic microangiopathies phenotypes

    Pathological and clinical data

    Time frame: 1/ Baseline, ie date of kidney biopsy

  2. Assess correlations between cause of thrombotic microangiopathies and clinical phenotypes

    Clinical data

    Time frame: 1/ Baseline, ie date of kidney biopsy

  3. Define the biological profile (standard biology and alternative complement pathway analyses including genetic data) of these thrombotic microangiopathies.

    Biological data

    Time frame: 1/ Up to 2 weeks after baseline date ; 2/ Date of last follow-up, an average of 2 years

  4. Define the renal, cardiovascular and vital prognosis of these patients

    Clinical data

    Time frame: 1/ Hospital discharge date, an average of 2 weeks ; 2/ Date of last follow-up, an average of 2 years

  5. Define treatments for these patients

    Clinical data

    Time frame: 1/ Hospital discharge date, an average of 2 weeks

06

Study locations

1 of 1 sites recruiting
07

References and documents

Publications

  • 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. PubMed 27989322 ↗
  • 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. PubMed 30862697 ↗
  • 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. PubMed 36509342 ↗

Individual participant data

Plan to share: Undecided

08

Registry details

Key details

Study ID
NCT05991245
Lead sponsor
University Hospital, Tours
Responsible party
Sponsor
First posted
Aug 14, 2023
Start date
Jan 1, 2023
Primary completion
Jan 2025 (estimated)
Completion
Jan 2025 (estimated)
Last update
Aug 14, 2023

Study contacts

Jean-Michel Halimi, MD, PhD
Contact
jmhalimi@univ-tours.fr
02.47.47.37.46 ext. +33
Valentin Maisons, MD
Contact
valentin.maisons@univ-tours.fr
02.47.47.37.46 ext. +33
Jean-Michel Halimi, MD, PhD
study director · CHRU TOURS, Nephrology
Valentin Maisons, MD
principal investigator · CHRU TOURS, Nephrology

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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