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

Impact of the Composition of the Packed Red Blood Cell Supernatant on Renal Dysfunction and Post-transfusion Immunomodulation

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

Study Overview

• Status: Completed
• Conditions: Renal Failure
• Intervention / Treatment: Other: PRBC transfusion

• Study Type: Observational
• Enrollment (Actual): 199

Contacts and Locations

Study Locations

• France
  • Nantes, France, 44093
    • CHU de Nantes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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;

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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)
• Currently taking antibiotics (except permitted peri-surgical antibiotic prophylaxis );
• History of advancing cancer;
• Clearance < 40 ml/min/m2 according to the Modification of Diet in Renal Disease (MDRD) during the pre-surgical assessment;
• Positive irregular antibody test warranting a cross-match prior to transfusion.
• Patients with indwelling urinary catheter preoperatively
• preoperative positive urine culture
• Urinary tract infection <21 days before surgery
• Background gesture on the upper or lower urinary tract

Exclusion criteria analysis

• In the renal insufficient group: Patient transfused plasma (s) Fresh Frozen (s) (PFCs) or concentrate (s) platelet (s) (CP) after the balance sheet T6 (6 hours after arrival in the ICU) and before the diagnosis of ARF,
• strict anuric patient not to achieve a 50 ml urine sample at least
• Reversal surgery requiring CEC before the 48th hour
• Surgical Complication could explain the acute renal failure (IRA)

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
link between the composition of the PRBC supernatant and the onset of renal failure	48 hours following surgery

Secondary Outcome Measures

Outcome Measure	Time Frame
Survival	1 year
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
Status at discharge from ICU: Dead/alive	day 28
Study of transfusion-related accidents recorded in ICU	within 28 days
Hospital admission, regardless of cause	1 year
Hospital admission due to infection	1 year
Diagnosis of cancer	1 year
Clinical course of pre-existing cancer	1 year

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Collaborators: Etablissement Français du Sang

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2016
• Primary Completion (Actual): March 23, 2022
• Study Completion (Actual): March 23, 2022

Study Registration Dates

• First Submitted: April 29, 2016
• First Submitted That Met QC Criteria: May 4, 2016
• First Posted (Estimated): May 5, 2016

Study Record Updates

• Last Update Posted (Actual): April 1, 2024
• Last Update Submitted That Met QC Criteria: March 29, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency
• Other Study ID Numbers: RC15_0420