Kent C. Cochrum

Deliberate donor-specific blood transfusions prior to living related renal transplantation. A new approach.

In order to select MLC incompatible one-haplotype related donor-recipient pairs that would achieve better graft survival and in an effort to alter the recipient immune response, 45 patients received three fresh blood transfusions from their prospective kidney donors. Recipient sensitization was evaluated by cross-match testing weekly sera obtained during and after the blood transfusions against donor T- and B-lymphocytes at 5 C (cold) and 37 C (warm). Thirteen (29%) of the 45 potential related recipients developed a positive warm T-cell cross-match or a persistent warm B-cell cross-match to their blood donor and related transplantation was not performed. Thirty-two (71%) patients had an appropriate negative cross-match to their blood donor. Thirty of these patients subsequently received kidneys from their blood donor. Ninety-seven per cent of the kidneys are functioning from one to 25 months with a single graft failure due to a patient discontinuing immunosuppressive medication. In addition to the excellent graft survival there was an unusually low incidence of rejection episodes in the recipients of kidneys from their blood donor so that the posttransplant course paralleled that of HLA-identical siblings. This approach may have future application with two-haplotype mismatched donor-recipient pairs, both related and unrelated.

Urological complications of renal transplantation can be prevented or controlled.

Our incidence of urological complications in 860 consecutive renal transplants in 3.4 per cent. A further reduction in incidence is demonstrated in the most recent 250 transplants of this series. Urological complications have been kept to a minimum by strict adherence to certain principles in donor nephrectomy, management of multiple and small arteries, and the technique of graft implantation. When urological complications were suspected early and judicious use of 131I hippurate scintiphotographic techniques has proved to be the most helpful method to evaluate patients. If a urological complication did occur prompt recognition and treatment were responsible for a high rate of graft salvage, low incidence of sepsis and absence of patient mortality.

Immunologic factors determining survival of cadaver-kidney transplants. The effect of HLA serotyping, cytotoxic antibodies and blood transfusions on graft survival.

We assessed immunologic factors determining graft survival in 510 recipients of primary cadaver allografts at one center. The degree of HLA match grade did not directly affect graft survival (54 per cent in no-antigen match, and 42 per cent in three-antigen match, at two years). There was no correlation between the HLA match grade and the degree of stimulation of the mixed lymphocyte culture. Patients receiving more than five blood transfusions had a significantly better graft survival than nontransfused recipients (52 versus 23 per cent, respectively, at two years, P less than 0.001). The beneficial effect of transfusions was noted whether or not lymphocytotoxic antibodies were produced, provided adequate screening was performed before transplantation. Transfusions did not alter the degree of stimulation in the mixed lymphocyte culture. More liberal use of transfusions and frequent screening for cytotoxic antibodies would probably result in more effective cadaver-kidney transplantation.

The impact of 1,000 renal transplants at one center.

A large, comprehensive renal transplant program has a major impact not only on patient care, but also on the medical center itself and the larger community. The program at this center has advanced from 15 transplants in 1964 to 141 transplants hi 1976. Fifty-nine per cent of patients transplanted have functioning kidneys at this time, including 76 children. Rehabilitation was equal to prerenal disease level in 91% of 169 recipients who lived five years with a functioning graft. Basic research in such diverse areas as renal preservation and immunology, as well as clinical research in optimum immunosuppressive therapy, resulted in significant contributions. Refinement of the mixed lymphocyte culture improved livingrelated graft survival at two years: 100% for HLA-identical and 91% for non-HLA-identical grafts, compared to 66% reported by the Transplant Registry for the combined group. Modification of immunosuppression improved patient survival at two years: 100% and 86% for recipients of living-related and cadaver grafts, respectively, compared to 83% and 65% reported by the Transplant Registry. The complexity of care of the patient with end-stage renal failure has required active interaction between transplant surgeons and almost every major specialty. The vast clinical material has been a great asset for training transplant surgeons, nephrologists, fellows and residents of multiple specialties, and medical students. The medical centers relationship with communities within a 250 mile radius has been strengthened, as reflected in patient referrals and the development of a multi-community-supported organ procurement system, which has allowed us to perform over 100 cadaver transplants per year for the past three years. Thus the performance of 1,000 renal transplants at this center has resulted not only in rehabilitation of many renal failure patients, but also in expanded and improved research and teaching capabilities, bringing support from multiple medical disciplines and the general community.

End Stage Polycystic Kidney Disease: Management by Renal Transplantation and Selective Use of Preliminary Nephrectomy

The results have been reviewed of 35 renal transplants performed on 31 patients with end stage polycystic renal disease. Patient survival is 81 per cent and 71 per cent of the patients have functioning grafts at an average followup of 3.1 years. The need for pre-transplant nephrectomy was evaluated early in the series and since then the operation has been practiced selectively. Twenty-two patients have received transplants with both polycystic kidneys in situ, while 2 patients have undergone transplantation after unilateral nephrectomy. In the absence of a history of renal infection or significant hematuria it has proved safe and desirable to leave the polycystic kidneys in situ. During the post-transplant period in such cases there has been no difficulty attributed to the in situ polycystic kidneys after more than 450 patient months of immunosuppressive therapy. The size of the polycystic kidneys has not been an indication of nephrectomy in our series and no significant technical difficulties have been encountered with large polycystic kidneys remaining in situ. Hypertension associated with end stage polycystic kidney disease has been controlled easily and has not proved an indication for pre-transplant nephrectomy.

The influence of donor age on graft survival

Recent papers report differing conclusions concerning use of kidneys from different donor age groups. We analyzed graft survival of 652 consecutive cadaver kidney donor-recipient pairs. Overall cumulative graft survival was 45 per cent at two years post transplantation. Kidneys from donors aged less that fifteen, sixteen to thirty. thirty-one to forty-five, and forty-six to sixty years had a cumulative graft survival of 51, 44, 39, and 40 percent, respectively. The difference is not statistically significant. When both donor and recipient ages are controlled, the pediatric aged kidney may be superior in the pediatric recipient or the older normotensive adult recipient. Use of properly selected cadaver kidneys in patients of all age ranges is encouraged.

Modification of the mixed lymphocyte reaction for pharmacokinetic assessment of immunosuppresive activity in human plasma

Abstract A modification of the two-way mixed lymphocyte culture (MLC) for the assessment of immunosuppressive activity in human plasma is proposed. Adding 50% of plasma instead of 10% to micro MLC increases the sensitivity and decreases the variability of the system used for pharmacodynamic analysis of prednisoloneand azathioprine combined with prednisolone. Harvesting the cultures on Day 3 augments the area under the inhibition time curve when compared with Day 5 and reduces the variability of the response of the MLCs. The method provides a time dependent measure of immunosuppression which may be correlated with pharmacokinetic parameters.

Do blood transfusions enhance the possibility of a compatible transplant

SUMMARY Blood transfusions prior to first cadaver kidney transplants have a significant beneficial effect on graft survival and, in this sense, appear to enhance the possibility of a compatible transplant. This desirable effect, however, occurs concomitantly with an increased degree of sensitization, which in turn reduces the likelihood of identifying a compatible kidney by direct crossmatch testing. This report illustrates that the beneficial effect is achieved with one to five transfusions prior to transplantation, but that more transfusions afford no additional benefits. In addition, the presence of cytotoxic antibodies per se does not have an adverse influence on graft survival. Liberal transfusion policies are therefore indicated in cadaver transplant candidates, but more than five transfusions prior to transplantation should probably be avoided unless clinically necessary.

Mycoplasma inhibition of phytohemagglutinin stimulation of lymphocytes.

Goat lymphocytes were cultured in vitro with phytohemagglutinin and nonviable mycoplasmas. Addition of the mycoplasmas, even as late as 45 hours after adding phytohemagglutinin, completely inhibited the increase in synthesis of DNA and RNA normally induced in lymphocytes by the mitogen. The suppression of synthesis did not result from killing of the cells by the mycoplasmas, combination of the organisms with phytohemagglutinin, or competition for combining sites on the cell surface, which indicates that some other mechanism of inhibition was operative. A similar depression of response to phytohemagglutinin in lymphocytes in culture has been observed in human diseases associated with an immune defect. The present demonstration that at least certain mycoplasmas can profoundly affect lymphocyte function in vitro suggests that thay may alter the immune response in vivo.

A ten year experience with cadaver kidney preservation using cryoprecipitated plasma

Between August 1967 and January 1977, 699 cadaver kidneys were preserved and transplanted in our hospital after continuous perfusion with cryoprecipitated plasma. Overall graft survival of primary transplants was 55 +/- 2 per cent at one year and 41 +/- 2 per cent at four years. The results with ninety-six second transplants were similar. The number of HLA antigens shared and the duration of preservation did not influence graft survival. Patient survival among 426 cadaver graft recipients since September 1972, when lower dose immunosuppression was started, was 91 +/- 1 per cent at one year and 84 +/- 2 per cent at four years, significantly better than survival before then. Survival of fifty-two recipients of cadaver retransplants since September 1972 was 86 +/- 5 per cent at one year and 86 +/- 5 per cent at four years, which was better than before. The incidence of posttransplantation dialysis was 30 per cent and did not correlate with the length of preservation. Primary wound infections, primary ureteral extravasation, and vascular complications each occurred with an incidence of 1.1 per cent or less in patients treated with lower dose immunosuppression. Only four kidneys were lost because of complications, and in no instance was the need for transplant nephrectomy directly related to the method of preservation. Perfusion preservation with cryoprecipitated plasma gives excellent results compared with alternative methods.