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

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

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)