Gary Niblack

The effect of first cadaver renal transplant HLA-A, B match on sensitization levels and retransplant rates following graft failure.

Data were collected retrospectively on all 449 first-transplant cadaver renal allograft recipients transplanted at four centers between 1/1/78 an 12/31/82 who had graft failure by 1/1/85. A total of 383 of these patients had information available regarding subsequent disposition. Of these, 182 (47.5%) were placed on an active waiting list for retransplantation. There were no associations found between placement on a waiting list and the following variables: panel reactive antibody (PRA) prior to first transplant or subsequent to graft failure, recipient age at first transplant or at the time of graft failure, recipient race, PRA after first graft loss, or HLA-A, B match of the first transplant. When stratified by level of HLA-A, B match as poor (0-1 antigen, n = 150) or good (2-4 antigens, n = 233) the poorly matched recipients as a group had a significantly lower mean PRA prior to first transplant (9.4 +/- 1.6 vs. 15.5 +/- 1.7, P less than 0.01), but a significantly higher PRA within the first year following graft failure (48.1 +/- 4.8 vs. 36.2 +/- 3.2, P less than 0.04). In addition, the poorly matched (vs. well-matched) group had a significantly higher mean increase in PRA following graft failure (45.1 +/- 4.4 vs. 33.7 +/- 3.5), and a significantly higher percentage of patients with PRA level greater than or equal to 60% within a year after graft failure (40% vs. 25%). Of the 182 patients who were placed on a waiting list, 113 (62.1%) were regrafted. As a group, regrafted patients had a significantly lower PRA within the first year following graft failure compared with the group not regrafted (33.6 +/- 3.9 vs. 54.0 +/- 5.0, P less than 0.002). Patients with a good first transplant HLA match had a higher overall regraft rate compared with those with a poor match (70.0% vs. 50.0%, P less than 0.01). Likewise, the percentage of well-matched patients regrafted within two years of first graft failure was significantly higher (55.5% vs. 32.5%, P less than 0.02). By multivariate analysis using the Cox proportional hazard model with 13 separate variables and considering all patients, the relative risk (RR) of not being regrafted was significantly (P less than 0.012) associated with poor HLA-A, B matching of the first transplant (RR = 1.7).(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of blood transfusion on cadaver renal transplantation: The southeastern organ procurement foundation prospective study (1977 to 1979)

The dominant beneficial effect of blood transfusions on cadaver renal allograft survival is now well established, although the mechanism of this phenomenon is unexplained. We evaluated data from a multicenter prospective series of 1,101 primary cadaver renal transplants done in the Southeastern Organ Procurement Foundation over a 30-month period. Data on pretransplant blood transfusions were obtained prospectively for transfusions given during the study period and retrospectively for blood transfusions given prior to the study. The administration of pretransplant blood transfusions was not randomized. The transfusion effect accounted for a 20% improved 1-year graft survival rate when the effect of antilymphocyte sera (ALS) and histocompatibility matching were factored out. The type of blood product was important. In patients who received only one type of blood product pretransplant, packed red blood cells (PRBC), washed red blood cells (WRBC), and mixed varieties of blood products (MRBC) were more effective than frozen red cells (FRBC) in achieving improved graft survival. The timing of pretransplant transfusions was important. PRBC, WRBC, and MRBC given 10 to 365 days pretransplant were highly effective while blood products administered at the time of renal transplantation and up to 10 days or over 1 year prior to transplant were less effective. ALS accounted for an average of 15% improved graft survival, but was most effective in the presence of previous transfusions and/or a high HLA match (0 or 1 HLA-A or B antigens mismatched). High HLA match accounted for a 9% improvement in graft survival in the transfused or ALS-treated recipient groups. Our study suggests that blood transfusions are the dominant beneficial factor in primary cadaver renal transplants, and that ALS and high HLA matching provide additional benefit. The best graft survival rates occurred with a combination of transfusions, ALS treatment, and high HLA match; the worst occurred with nontransfused recipients who did not receive ALS and had low HLA match. We showed no graft effects relative to age, HBsAg antigenemia, sex, parity, blood group, or preformed cytotoxic antibody status. It is now clear from reports of over 100 transplant centers that blood transfusions before cadaver renal transplantation exert a beneficial transfusion effect (TE) on graft survival. The practical implications of this finding are still being critically assessed, since the accuracy of the report data is inherently subject to recording errors, and various factors influencing the success of renal transplantation are easily confounded with TE. Few randomized prospective studies have been done on a large enough scale for interpretation, and much of the transfusion history of renal transplant recipients is necessarily retrospective (1). Furthermore, there is caution in accepting a liberal transfusion policy since preformed antileukocyte antibodies may make it difficult or impossible to obtain a cadaver kidney for presensitized patients. Also, hyperacute rejections may occasionally occur even when antibodies cannot be detected by the usual tests. Finally, the risk of hepatitis transmission is as high as 10%, a substantial danger (2). How efficacious is blood transfusion for cadaver renal transplantation, and how can we separate its effects from those of ALS, HLA matching, and other treatment variables? Is the TE synergistic with or antagonistic against other graft-enhancing therapeutic options? In order to assess these questions, the data from a prospective study of the Southeastern Organ Procurement Foundation were critically analyzed. This preliminary report covers 1,101 primary cadaver renal allografts. It confirms the dominant effects of transfusion on cadaver renal grafts and further clarifies the therapeutic value of ALS and HLA matching.

Bilateral Nephrectomy Concomitantly with Renal Transplantation

During a 2-year interval 206 patients underwent renal transplantation at a single center, 38 of whom underwent bilateral nephrectomy and other adjuvant operations as part of the transplant procedure. The indications for this type of procedure were reviewed, with special emphasis on the control of hypertension. The morbidity and mortality (16 per cent) in this group were compared in detail to those in patients not undergoing a concomitant adjuvant operation. The results with regard to renal function were similar to the group as a whole and the indications for appropriate patient selection are discussed.

Why Do Secondary Cadaver Renal Transplants Succeed? Results of the South-eastern Organ Procurement Foundation Prospective Study, 1977-1982

We report the selective and therapeutic factors affecting multiple kidney transplant success from a prospective multicenter study of the South-Eastern Organ Procurement Foundation. From June 1977 to March 1982, 3,215 cadaver kidney transplants were performed at 39 institutions. There were 2,535 first, 564 second, 103 third and 13 fourth grafts. The actuarial graft survival rates at 1 and 2 years were 52 plus or minus 1 and 45 plus or minus 1 per cent, respectively, for first grafts, 44 plus or minus 2 and 40 plus or minus 3 per cent for second grafts, and 42 plus or minus 5 and 31 plus or minus 6 per cent for third grafts. Graft survival rates were significantly lower for second and third than for first transplants (p less than 0.003). There was no difference in patient survival rates. The data were analyzed to determine which selective and therapeutic variables governed success of primary and secondary grafts. Pre-transplant blood transfusions were associated with a significant increase in graft survival rates in primary (p less than 0.00005) and secondary transplants (p less than 0.01), and did not affect patient survival rates. The administration of antilymphocyte serum also improved graft survival rates significantly in primary (p less than 0.00005) and secondary grafts (p less than 0.00002), without alteration of patient survival rates. HLA compatibility improved primary graft survival rates (p less than or equal to 0.022) but this did not reach statistical significance in secondary graft survival rates. Second transplant graft survival rates were best when the primary graft functioned for more than 12 months (Breslow p less than or equal to 0.02) but were not related to the reason for loss of the first graft. Pre-transplant bilateral nephrectomy improved graft survival rates significantly but this phenomenon was linked to other treatment factors. No beneficial effect on graft survival rate could be shown after pre-transplant splenectomy in patients with primary or secondary grafts and this procedure was associated with reduced patient survival rates in both groups.

Use of SEOPF regional crossmatch trays to share kidneys for sensitized patients. Local experience of three centers.

Regional organ procurement (ROP) crossmatch trays are used by members of the South-Eastern Organ Procurement Foundation (SEOPF) to facilitate sharing of cadaver kidneys for highly sensitized patients. ROP trays carry a single representative serum sample from over 900 patients with panel reactive antibody (PRA) levels of ≤60%. Trays are centrally prepared periodically and distributed to member laboratories where they are used for preliminary crossmatching against locally obtained donors. Crossmatching results are used in conjunction with the SEOPF computer match program for sharing of kidneys. Proficiency testing studies by the 40-member laboratories show a >90% concordance rate on results with these highly and broadly reactive sera. Data were available from 3 centers on 74 kidneys shared between SEOPF-member institutions on the basis of a remote, preliminary, negative ROP tray crossmatch. Of these, 44 (59%) crossmatched negative locally with the same and other sera, and were thus considered acceptable to be transplanted to the intended highly sensitized patients. Sixteen (22%) donors had a positive crossmatch locally, but with sera other than that present on the ROP tray used for screening. In 14 cases (19%) the same serum as on the ROP tray gave a positive crossmatch. The majority of ROP tray inconsistencies appeared to be due to use of more sensitive crossmatching techniques at the recipient center. Of the 27 patients transplanted at these 3 centers with kidneys received on the basis of ROP tray results, none experienced hyperacute or early irreversible rejection and actual graft survival at 6–48 months is 74%. These studies indicate that regional sharing of patient sera by the existing network of histocompatibility testing laboratories is an effective and reliable mechanism to identify crossmatch-negative donors for highly sensitized patients.

The role of HLA tissue matching in cadaveric kidney transplantation.

The role of HLA match in donor-recipient selection has been studied in 271 patients who received cadaver transplants during a 10-year period. This series included 36 four-antigen matches, 181 three-antigen matches and 54 two-antigen matches. Our results support the concept that bettor results can be expected when better matched kidneys are utilized for transplantation.