Significant Reduction of Proinflammatory Cytokines by Treatment of the Human Brain Dead Donor

Abstract

Body:The matching was performed on 1300 kidney transplants from a single center population of transplants between 1996 and 2001. When samples were taken singly from 0 to 6 mismatch, there was an increased graft survival for each match grade examined. Most commonly, differences were more pronounced with time, however, 0,1,2 mismatch groups had smaller numbers. Therefore, 0,1,2 mismatch were combined as Group I and Ͼ2 mismatch as Group II. We found approximately 2% increase in graft survival per year for Group I as compared to Group II. This 2% was additive over the first 5 years examined. Interestingly, we could show that Group I was associated with lower average trough level for both immunosuppressed groups (neoral and tacrolimus). This was empirical and not done with any prospective immunosuppressive protocol. Furthermore, the patient survival was higher in Group I (pϭ.001). Conclusion: Matching from a single large center has shown efficacy at comparing 0,1,2 mismatches to Ͼ2 mismatch. Patient survival and lower immunosuppression was indicative of shorter hospital stay, less rejection, and fewer complications.Aims: Since Sept. 20, 1999 our organ procurement organization (OPO) that serves an ethnically diverse local distribution area has allocated kidneys from deceased donors using a UNOS approved kidney allocation variance that awards 7 points for a 0-CREG,0-DR mismatch (MM) and 6 points for a 0-A,B MM. Points were also given for waiting time (3) and panel-reactive antibodies (PRA) Ͼ80% (3). Previously we showed that awarding points for 0-CREG,0-DR MM in kidney allocation improves the access to HLA matched transplants for all racial groups, especially the black race. In this study we evaluated if there are graft outcome benefits as well. Methods: One and 3 year uncensored graft survival (GS) data were provided by Scientific Registry of Transplant Recipients (SRTR) and analysed for the influence of HLA mismatching on graft outcome in black and non-black recipients. Results: Overall, 1 year GS was 87.4% (Nϭ1,197) and not significantly different for blacks (86.1%, Nϭ467) and non-blacks (88.2%, Nϭ730); 3 year GS was 74.6% (Nϭ1,245) and significantly lower for blacks (68.5%, Nϭ480) vs. non-blacks (78.4%, Nϭ765), pϭ0.0001. * ϭ less than 30 cases No significant improvement in GS (pϭNS) was seen with HLA matching, including 0-CREG, 0-DR MM, for either the black or non-black recipients (Table) and also not seen when data was stratified for patients non-sensitized (PRAՅ10%) and sensitised (PRA Ͼ10%) at the time of transplant. Of those relisted after a failed graft, the 0-A,B,DR MM group was the least sensitized (6%, Nϭ16) as expected, and there was a trend for less sensitization in the 0-CREG,0-DR MM group (33%, Nϭ9), compared to those with other HLA mismatches (67%, Nϭ126). Conclusions: In conclusion, based on 1-year and 3-year follow-up data, there are no apparent graft oucome benefits for either CREG matching or conventional HLA matching in our service area. Such benefits may become apparent with longer follow-up.

Composite Tissue Allotransplantation Immunology

“…The fact that organs from living donors are superior to those of cadaveric donors suggests that brain death can influence graft quality and can cause rapid swings in blood pressure, hypotension, coagulopathy, pulmonary changes, hypothermia, and electrolyte abnormalities [ 31 32 ]. Organ removal, storage, total ischemia time and engraftment may increase the immunogenicity of allografts by upregulating MHC antigens and activating the cytokine adhesion molecule cascade, which in turn leads to leukocyte infiltration and, ultimately, obliterative vasculopathy and fibrosis [ 33 34 ]. Coping with allograft rejection may be much more difficult in CTA than in other forms of transplantation.…”

Hypothalamic-pituitary axis disorder – “the puppet master” of multiple organ dysfunction in brain-dead patients

“…Hypotension occurs because of hypovolemia, myocardial dysfunction, inadequate fluid repletion or restriction, use of diuretics or depletive treatment for previous cerebral edema, hyperosmolar therapy, third space losses, hemorrhage and/or diabetes insipidus. The severe inflammatory response occurred shortly after the irreversible loss of brain function is responsible for a marked vasoplegia, capillary leak and left ventricular dysfunction [ 7 ]. The alterations in hormonal production and regulation secondary to the cessation of blood supply of the hypothalamic-pituitary axis causes hypothyroidism and hypocortisolism and the lack of antidiuretic hormone.…”