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

Renal Failure Clinical Trial

— TRANSNEPHRON  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02763410
• Other study ID #: RC15_0420
• Status: Completed
• Start date: September 8, 2016
• Est. completion date: March 23, 2022

Study information

• Verified date: March 2024
• Source: Nantes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 199
• Est. completion date: March 23, 2022
• Est. primary completion date: March 23, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Renal Failure
• Renal Insufficiency

Intervention

Other:
• PRBC transfusion

Locations

Country	Name	City	State
France	CHU de Nantes	Nantes

Sponsors (2)

Lead Sponsor	Collaborator
Nantes University Hospital	Etablissement Français du Sang

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	link between the composition of the PRBC supernatant and the onset of renal failure		48 hours following surgery
Secondary	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
Secondary	Number of dialysis days		within 28 days
Secondary	Duration of stay		within 28 days
Secondary	Ventilation period (in hours);		within 28 days
Secondary	ICU-acquired infection		within 28 days
Secondary	Status at discharge from ICU: Dead/alive		day 28
Secondary	Study of transfusion-related accidents recorded in ICU		within 28 days
Secondary	Hospital admission, regardless of cause		1 year
Secondary	Hospital admission due to infection		1 year
Secondary	Diagnosis of cancer		1 year
Secondary	Clinical course of pre-existing cancer		1 year
Secondary	Survival		1 year