Clinical trial NCT05399420: Study of Kidney Circulating Cell-free DNA in Patients With Acute Kidney Failure
Official title: Study of the Quantitative Evolution of Circulating Cell-free DNA of Renal Origin in Patients With Acute Renal Failure
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Kidney Failure, Acute
Lead sponsor: CGenetix
Sponsor class: INDUSTRY
Collaborators: name: Centre Hospitalier Sud Francilien
First posted: 2022-06-01
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients admitted in nephrology service for symptome suggesting a functional or organic kidney failure.

Brief summary: The amount of total circulating DNA has been shown to increase in patients with acute renal failure. Nevertheless, it is currently not currently possible to prove the renal origin of this circulating DNA. Recently, in healthy subjects, teams have shown that it is possible to identify its tissue origin of circulating DNA. CGenetix is a MedTech company which develops on an identical principle an in vitro diagnostic test capable of identifying and quantifying renal degradation during an acute trauma. The objective of this study is to evaluate the sensitivity of the proposed technology to detect circulating DNA of renal origin released into the general circulation in patients with acute organic and functional renal failure. Patients with functional or organic kidney deficiency will be included and the kidney biomarkers develop by CGenetix will be compared between these 2 groups of patients.

Detailed description: When the patient arrives, a first stage of checking the inclusion/non-inclusion criteria will be respected. Patients who do not meet the eligibility criteria will not be sampled (pre-screening stage).

Patients meeting the eligibility criteria will be informed of the study by the investigator and a written information note will be given to them. If they do not object to their participation, an additional tube of blood for research purposes will be taken during a blood sample taken as soon as they are admitted as part of their usual treatment. They will also follow the standard care protocol according to the clinical recommendations of their attending physician. The objective of early sampling is to sensitize the test by assaying the marker as soon as possible after renal injury. In the event of a posteriori differential diagnosis (obstructive ARF or IRC), the patient will be excluded from the final analysis.

Patients passing the pre-screening and screening stages positively will be included in the final analysis.

90 patients should be included and divided into 2 groups:

* 65 patients with non-biopsied organic acute kidney injury of which 20 patients with biopsied organic acute kidney injury (test group)
* 25 patients with functional acute kidney failure (control group).

Eligibility criteria: Inclusion Criteria:

* Age \> 18 years old
* Admitted for suspicion of acute renal injury (organic) and/or with an indication for renal biopsy (PBR)
* Patients hospitalized with functional acute renal failure (negative control and inclusion limited to n = 30 maximum)

Exclusion Criteria:

* Patients \< 18 years old
* Patients with cognitive and mental disorders making them unable to express their non-objection to participation in the study
* Patients with obstructive renal failure
* Patients with chronic renal failure
* Patients who expressed their refusal to participate in the study

Primary outcomes:
measure: Quantification of circulating cell-free DNA of renal origin at baseline (at patient hospital admission in nephrology department)
timeFrame: Patient hospitalization time
Secondary outcomes:
measure: Comparison of circulating-cell-free DNA of renal origin amounts and kidney biopsy results at baseline (at patient hospital admission in nephrology department)
timeFrame: Patient hospitalization time
Other outcomes:
Locations:
Study officials:
affiliation: Centre Hospitalier Sud Francilien
name: Valerie Caudwell, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bloom RD, Bromberg JS, Poggio ED, Bunnapradist S, Langone AJ, Sood P, Matas AJ, Mehta S, Mannon RB, Sharfuddin A, Fischbach B, Narayanan M, Jordan SC, Cohen D, Weir MR, Hiller D, Prasad P, Woodward RN, Grskovic M, Sninsky JJ, Yee JP, Brennan DC; Circulating Donor-Derived Cell-Free DNA in Blood for Diagnosing Active Rejection in Kidney Transplant Recipients (DART) Study Investigators. Cell-Free DNA and Active Rejection in Kidney Allografts. J Am Soc Nephrol. 2017 Jul;28(7):2221-2232. doi: 10.1681/ASN.2016091034. Epub 2017 Mar 9.
citation: Merkle J, Daka A, Deppe AC, Wahlers T, Paunel-Gorgulu A. High levels of cell-free DNA accurately predict late acute kidney injury in patients after cardiac surgery. PLoS One. 2019 Jun 18;14(6):e0218548. doi: 10.1371/journal.pone.0218548. eCollection 2019.
citation: Oellerich M, Sherwood K, Keown P, Schutz E, Beck J, Stegbauer J, Rump LC, Walson PD. Liquid biopsies: donor-derived cell-free DNA for the detection of kidney allograft injury. Nat Rev Nephrol. 2021 Sep;17(9):591-603. doi: 10.1038/s41581-021-00428-0. Epub 2021 May 24.