Terasaki Pi

KIDNEY PRESERVATION FOR TRANSPORTATION: Initial Perfusion and 30 Hours' Ice Storage

Abstract A method was developed by which Summary kidneys could be shipped in a small box containing ordinary ice for periods of up to 30 hours with almost no detectable damage. A total of 54 dog kidneys were stored in saline at 0°C with ice slush for 16, 24, and 30 hours, using surface cooling alone or combined with initial perfusion with several solutions. To evaluate the efficacy of storage, the contralateral kidney was removed at the time of reimplantation of the stored kidney and blood levels of creatinine and urea were followed daily. The final relatively simple scheme (infusion of mannitol, phenoxybenzamine, and a special perfusate) resulted in uniformly good preservation in all 7 kidneys stored for 24 hours and all 3 kidneys stored for 30 hours (there was one technical failure). Other perfusates, such as Ringers lactate and 10% invert-sugar solutions, gave inferior results. The new perfusate extended the time of simple ice storage from 12 hours to 30 hours.

Analyses of the unos scientific renal transplant registry at three years-yearly events affecting transplant success

The success of cadaveric renal transplants in the first year is determined largely by events that transpire during the transplant hospitalization. This conclusion is based upon analyses of data on 19,525 cadaver donor renal transplants performed since October 1987 and reported to the UNOS Scientific Renal Transplant Registry from more than 200 centers nationwide. Graft survival rates at 1 year differed by 20–30% depending upon whether or not the transplanted kidney functioned immediately and upon whether the patient required dialysis during the first week posttransplant, experienced rejection, or was discharged with a kidney that was functioning well. Recipients whose discharge serum creatinine level was less than 2.6 mg/dl or whose graft was functioning well at the time of discharge had 88% 1-year graft survival. A multistep logistic regression analysis showed cold ischemia time, transfusions, donor age and cause of death, HLA-DR mismatches, and peak

POOR KIDNEY-TRANSPLANT SURVIVAL IN RECIPIENTS WITH FROZEN-BLOOD TRANSFUSIONS OR NO TRANSFUSIONS

Abstract The one-year cadaver-kidney survival-rate in 93 recipients who had not been exposed to transfused white blood-cells prior to transplantation was 28±6%, which was significantly lower than the 53±4% survival-rate of 197 cadaver transplants in patients who were known to have been transfused (p

The relative effects of FK506 and cyclosporine on short- and long-term kidney graft survival.

As reported to the UNOS Kidney Transplant Registry from 1988 through 1994, 544 first cadaveric kidney graft recipients have been discharged with maintenance tacrolimus (FK506) therapy. Total follow-up data was available on 38,057 first cadaveric kidney transplants from 224 centers reporting at least 10 grafts each to the Registry. We examined the effects of FK506 on short- and long-term renal graft outcomes and compared its effect with that of cyclosporine (CsA). Three drug categories (FK506, CsA, and Other) were defined using therapies through discharge (i.e., grafts surviving more than 15 days). The 1-year graft survival rate of 2366 recipients receiving Other therapies was 69.2 +/- 1.0%. By comparison, both FK506 and CsA recipients demonstrated significantly improved early graft function (1-yr survival rates of 91.1 +/- 1.3% and 86.6 +/- 0.2%, respectively). The long-term graft survival, as measured by half-lives, varied little (8-9 yr) between Other and CsA groups, but was significantly (P = 0.04) increased for FK506 patients (to approximately 14 yrs). CsA usage was reported by all 224 transplant centers, whereas FK506 was administered at only 24 (11%) centers. Using multivariate methods, a drug regimens graft survival rate was adjusted for center effects and 19 covariates. The adjusted FK506 and CsA cadaveric graft survival rates at 1 and 3 years mirrored their unadjusted rates, indicating that demographic differences did not confound our results. Based on this study, FK506 appears to be the first therapeutic agent to significantly improve long-term kidney graft survival rates.

HLA-DRW4 IN 91% OF JEWISH PEMPHIGUS VULGARIS PATIENTS

HLA-DRW4 was found in all 11 female and 10 out of 12 male Jewish patients with pemphigus vulgaris, a frequency of 91% in all, which was significantly higher than the 25% frequency among normal Jewish controls. The relative risk was 31.5. The BW38-DRW4 haplotype occurred in 12 out of 22 patients (55%) but in only 2% of White non-Jews and 11% of normal Jewish people.

Lymphocytotoxic antibody responses to transfusions in potential kidney transplant recipients.

A series of 737 hemodialysis patients were studied for the relationship between lymphocytotoxic antibody formation and blood transfusions; 331 thereof were studied prospectively. With up to 20 transfusions, highly reactive (greater than 90% reactivity against random panel) antibodies were not found in any of the prospectively studied males or females without previous pregnancies. Nearly 90% of the males failed to form antibodies against greater than 10% of the panel donors. Patients with previous pregnancies developed antibodies at a much higher rate. Among 316 patients tested, antibodies against B cells were found more frequently than antibodies against T cells. Both T and B cell antibody levels often decreased in spite of additional transfusions. It is concluded that the risk of rendering a patient untransplantable because of sensitization as a result of transfusions is very small.

INDUCTION OF HIGH KIDNEY GRAFT SURVIVAL RATE BY MULTIPLE TRANSFUSION

In 33 centres that adopted a policy of liberal preoperative blood transfusion 174 recipients of cadaver donor transplants were followed up. Those who received no pretransplant transfusions had a 23% 1-year graft survival rate whereas those who had greater than 10 transfusions had an 87% survival rate (p less than 0.000001). 3% of those transfused acquired highly reactive cytotoxic antibodies and greater than 70% had no antibodies, so transfusions do not exert their beneficial effect by excluding strong immune responders. Since transplant survival rates improved with the number of transfusions, they probably produce their beneficial effect by inducing a state of unresponsiveness. Multiple transfusion seems a simple and effective way of improving kidney transplant survival rates. Moreover, the immunosuppressive effect is specific in that it does not alter the immune response to infectious agents.

IDENTIFICATION OF UNRESPONSIVE KIDNEY-TRANSPLANT RECIPIENTS

Abstract Non-presensitised kidney-transplant recipients, defined by the absence of lymphocytotoxic antibodies in their serum before transplantation, were divided according to the length of time they were free of cytotoxins. Recipients of cadaver kidneys who had not developed cytotoxic antibodies during haemodialysis treatment of more than one year before transplantation subsequently had a high kidney-transplant survival-rate at one year of 85% in contrast to a 50% survival-rate for recipients who did not develop cytotoxins during a haemodialysis period of less than one year. The statistical significance of the difference between these two groups, comprising 48 and 214 patients, respectively, was (P

SUPPRESSION OF LYMPHOCYTE TRANSFORMATION BY ASPIRIN

Abstract Aspirin in physiological dose ranges (10-40 mg. per 100 ml. plasma) has been shown to inhibit the incorporation of 3 H-thymidine in the lymphocyte transformation reaction in response to phytohaemagglutinin (P.H.A.) and allogeneic human lymphocytes. The inhibition was not due to the toxicity of the drug, for the lymphocytes responded well after washing out the aspirin. Later stages in D.N.A. synthesis appear to be involved, since aspirin was effective even 3 days after initial stimulation with P.H.A. Sodium salicylate suppressed lymphocyte transformation but salicin did not. Another related compound, o -hydroxyphenylacetic acid, did not affect the P.H.A. response but was definitely suppressive to allogeneic response.

HL-A and kidney transplants: reexamination.

SUMMARY Graft survival was analyzed in over 3,000 human kidney transplants performed between 1969 and 1972, with respect to histocompatibility. The most significant factors on graft survival were found to be HL-A haplotype differences, unresponsiveness to HL-A, and presensitization to HL-A. In cadaver donor transplants, HL-A antigen differences (HL-A matching) seemed to be of some influence, although not of statistical significance; no substantial improvement was obtained when cross reactivity and homozygosity were considered. Contrary to the reports of others, second locus antigens were not more significant than the first locus antigens. The HL-A type of the recipient and mismatches for different HL-A specificities were not found to be factors of major influence on graft survival. For cadaver kidney transplantation, immune responsiveness to HL-A as measured by antibody production to HL-A was the most consistent factor influencing survival of transplants.