Wideman Ca

Multivariate Analysis Of Risk Factors Impacting On Immediate And Eventual Cadaver Allograft Survival In Cyclosporine-treated Recipients

A multivariate analysis dissected the impact of donor procurement variables, immunologic risk factors, and alternate cyclosporine and prednisone induction immunosuppressive regimens on the early and eventual function of 303 consecutive cadaveric renal allografts. Primarily warm, but to a slight extent cold, ischemia time had an adverse impact on allograft function, as did the requirement for vasopressor or diuretic therapy. The occurrence of initial graft nonfunction adversely affected the probability of three-month graft survival, but did not alter either the longevity of organs, which subsequently recovered function, or patient mortality rate. The major immunologic risk factor was a second or multiple transplant, which was associated with an increased incidence of early graft failure, and impaired renal function in successful transplants. Correlations with HLA-B and DR matching were reflected in the quality of renal function, but not in graft survival rates. Cyclosporine (CsA) administration by continuous intravenous infusion, in order to avert initial elevated mean three-day, serum radioimmunoassay drug levels reduced the incidence of initial graft non-function. High levels were also associated with impaired early and eventual renal function. Rapid posttransplant taper of corticosteroids to 30 mg prednisone by day six was associated with a greater incidence of rejection episodes and early graft failure than a taper that achieved 30 mg prednisone at 60 days. Both the serum creatinine value and the degree of hypertension observed at one month afforded good prognostic indices of eventual graft survival. Therefore, renal allografts in CsA-treated patients were sensitive not only to adverse donor and immunologic risk factors, but also to excessive CsA drug levels in the early postoperative period. These findings suggest an induction immunosuppressive strategy utilizing slightly higher initial doses of steroids for CsA-sparing during the first three days, followed by increased, but judicious, administration of CsA to achieve steroid-sparing by virtue of effective rejection prophylaxis.

Impact of Cyclosporine on Renal Transplant Practice at the University of Texas Medical School at Houston

CsA has improved the outcome of renal allotransplantation with CAD and LRD kidneys. CsA mitigates risk factors heretofore presenting substantial obstacles to CAD transplantation: HLA matching, pretransplant splenectomy, extensive numbers of conditioning blood transfusions, and old age. In LRD transplantation, CsA obviates the need for donor-specific transfusions in the haploidentical situation, and for prednisone in the HLA-identical setting. The incidence of drug-induced nephrotoxicity beyond six months is 30% with the degree of dysfunction proportionate to the degree of histo-incompatibility, suggesting that subclinical allograft rejection due to overzealous dose reduction may compromise allograft function. At present, total conversion from CsA to Aza appears ill-advised; even patients who never suffered allograft rejection under CsA therapy frequently lose their allograft when the inferior level of Aza suppression is substituted. Drug-induced hypertension, a modestly significant factor, diminishes further by two years posttransplant. The benefit of CsA therapy is a reduced incidence of 19% initial and 10% recurrent rejection episodes. Of great importance is the observation that 17% of rejection episodes followed patient noncompliance. Further, the incidence of bacterial infections was greatly reduced, and viral infections modestly lessened. Only the occurrence of pneumocystis carinii was increased, but 92% of patients survived in spite of serious pulmonary infection. Development of a consistent CsA regimen has reduced the median initial hospitalization to 12.5 days for LRD and 14 days for CAD, a level well within the range stipulated for the Disease-Related Guidelines of the Medicare Program. Furthermore, readmission is less frequent; one-third of patients never reenter the hospital.(ABSTRACT TRUNCATED AT 250 WORDS)

Parent-to-child transplantation with cyclosporine immunosuppression

The use of cyclosporine, a fungal endecapeptide immunosuppressive agent, has greatly improved the outcome of haploidentical transplantation in adults, but less impressively improved the result of parent to child transplantation. The incidence of allograft loss and treated rejection episodes was much greater in pediatric than in adult recipients, and the evidences of nephrotoxicity lessened. Although resistance of the childs immune system to the effects of the drug cannot be excluded, it appears more likely that this relates to the rapid clearance of the agent in the pediatric age group (39.6 mL/min/kg) versus in adults (12.3 mL/min/kg), thereby reducing the area under the serum concentration curve from 765±593 to 386±277 ng/mL/hr per mg/kg (mean±SD). This effect caused trough serum levels measured by radioimmunoassay to be below the putative threshold. These findings demonstrate the need for higher cyclosporine doses and frequency in pediatric compared with adult patients.

Does cyclosporine influence the results of cadaver retransplantation

The results of cadaveric retransplantation in 55 recipients immunosuppressed with cyclosporine and prednisone were compared to 156 recipients of primary renal allografts. By 3 yr posttransplant, there is no significant difference in patient survival, but the yearly graft survival for primary (79%, 72%, 72%) as compared to retransplant (69%, 58%, 58%) recipients was significantly (p less than 0.05) better. There was no significant difference in rejection episodes or mean +/- SD serum creatinine (mg/dl) at 2 yr between primary (32%, 2.14 +/- 1.1) and retransplant (33%, 2.08 +/- 1.4) patients, respectively. Donor source, third kidneys, human leukocyte antigen AB and Dr matching, percent reactive antibody levels, and cause of first graft loss do not have significant impact on cyclosporine-treated retransplant outcome. However, retransplant patients who have lost a previous graft in less than 3 months continue to be at high risk for subsequent early graft loss. These results suggest that the combination of cyclosporine and prednisone is the preferred regimen for cadaveric retransplantation.

Parent-to-Child Transplantation With Cyclosporine Immunosuppression

The use of cyclosporine, a fungal endecapeptide immunosuppressive agent, has greatly improved the outcome of haploidentical transplantation in adults, but less impressively improved the result of parent to child transplantation. The incidence of allograft loss and treated rejection episodes was much greater in pediatric than in adult recipients, and the evidences of nephrotoxicity lessened. Although resistance of the childs immune system to the effects of the drug cannot be excluded, it appears more likely that this relates to the rapid clearance of the agent in the pediatric age group (39.6 mL/min/kg) versus in adults (12.3 mL/min/kg), thereby reducing the area under the serum concentration curve from 765 +/- 593 to 386 +/- 277 ng/mL/hr per mg/kg (mean +/- SD). This effect caused trough serum levels measured by radioimmunoassay to be below the putative threshold. These findings demonstrate the need for higher cyclosporine doses and frequency in pediatric compared with adult patients.