Impact of the Composition of Packed Red Blood Cell Supernatant on Renal Dysfunction and Posttransfusion Immunomodulation

NCT02763410 | Completed DMC

• 1 other identifier: RC15_0420
• Study Type: observational
• Target: 199
• Locations: 1 country
• Sites: 1

Brief Summary

Safety during transfusions is a major issue in medical economics. Despite drastic quality control measures, transfusion is still a source of short, mid and long-term morbi-mortality. This can be explained to some extent by changes in the composition of the packed red blood cell (PRBC) supernatant during storage essentially with the appearance of immunologically active compounds possibly involved in organ dysfunction on the one hand and post-transfusion immunomodulation on the other hand. These phenomena impact upon outcomes for cardiac surgery patients. In terms of organ dysfunction, kidney failure due to acute tubular necrosis and pulmonary failure are the 2 main issues. Following cardiac surgery, 11% of patients will present with transient renal dysfunction characterised by a 25% increase in serum creatinine levels and 3.5% require dialysis. The intensity of acute renal failure (ARF) is correlated to resuscitation : a 20% increase in serum creatinine levels 2 to 3 days after surgery significantly raises morbidity rates and a 50% increase raises the mortality rate to 10%. The precise mechanisms governing post-transfusion immunomodulation have not yet to be defined. The appearance of soluble type I Human leukocytes Antigen (HLA) molecules (sHLA-I), the FAS ligand (FAS-L) or cluster designation 40 (CD40-L) in the supernatant of PRBCs along the storage of blood products may be involved in such phenomena. These molecules are capable of activating or triggering the death of innate or adaptive immunity cells, especially the Natural Killer (NK) cells. Consequently the investigators propose to focus specifically on the detailed composition of transfused PRBC supernatants in order to identify the candidate molecules responsible for organ dysfunction or post-transfusion immunoparalysis. The investigators will combine a clinical approach based on the transcriptional analysis of renal tubular cells in transfused patients and an ex-vivo approach investigating the effect of the supernatant on immune cells and the Natural Killer cells of healthy volunteers

Conditions

Renal Failure

Outcome Measures

Primary Outcomes (1)

• link between the composition of the PRBC supernatant and the onset of renal failure

  48 hours following surgery

Secondary Outcomes (12)

• Respiratory dysfunction in the ICU defined by a blood pressure of oxygen (PaO2)/inspired oxygen fraction (FiO2) ratio < 300 on at least one occasion

  within 28 days

• Number of dialysis days

  within 28 days

• Duration of stay

  within 28 days

• Ventilation period (in hours);

  within 28 days

• ICU-acquired infection

  within 28 days

Study Arms (2)

control group

Patients who received between 1 and 5 PRBCs between incision and the 6th hour post-surgery, with no renal failure at the 48th hour after surgery, based on the RIFLE classification, and regardless of the transfusion received after the H6 assessment.

Other: PRBC transfusion

Renal failure group

Patients who received between 1 and 5 PRBCs between incision and the 6th hour post-surgery and who developed renal failure before H48 with no new transfusion prior to diagnosis of kidney failure.

Other: PRBC transfusion

Interventions

PRBC transfusion OTHER

Renal failure group; control group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients: The investigators selected cardiac surgery patients for the transfusion frequency and significant post-surgical renal morbidity. Study centre: The study will take place at the CHU Nantes (University Hospital Centre) where over 1500 extracorporeal circulation procedures are performed annually. Number of patients required: 200 patients: 100 transfusion patients who have developed renal failure; 100 transfusion patients who have not developed renal failure;

You may qualify if:

• Non-emergency cardiac surgery under extracorporeal circulation (CEC) with cardioplegia:
• And no indication of pre-surgical PRBC transfusion (priming excluded), And no indication of transfusion with fresh frozen plasma or pre-surgical platelet concentrate

You may not qualify if:

• Heart and/or lung transplant surgery;
• Emergency surgery to be performed within 24 hours;
• Patient \<18 years old;
• Pregnant woman
• Protected adult
• Adult incapable of expressing his/her non-opposition
• Opposition expressed by the patient on recording his/her data;
• No French social security;
• Patient who underwent a transfusion in the 3 months prior to surgery;
• Surgery due to endocarditis or suspected endocarditis;
• Myocardial infarction \< 15 days;
• Patient receiving inotropic or vasopressor prior to surgery;
• Patient receiving immunosuppressant treatment;
• Patient receiving corticosteroids for 21 days or more;
• Seropositive patient known to be suffering from HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV)

Sponsors & Collaborators

• Nantes University Hospital: lead
• Etablissement Français du Sang: collaborator

Study Sites (1)

CHU de Nantes

Nantes, 44093, France

Location

Biospecimen

Retention: SAMPLES WITH DNA

urine samples and PRBC tubing

MeSH Terms

Conditions

Renal Insufficiency

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2016
• First Posted: May 5, 2016
• Study Start: September 8, 2016
• Primary Completion: March 23, 2022
• Study Completion: March 23, 2022
• Last Updated: April 1, 2024

Record last verified: 2024-03

Locations

FR (1)