Experience with cyclosporine in adult living donor kidney transplantation: From 1984 to 2002 at Yonsei University

Indications:Kidney graft rejection prophylaxis in 1900 patients undergoing living donor kidney transplantation.

Patients:1900 patients (1802 primary, 96 second, and 2 third transplants from 955 living related [LRD] and 945 living unrelated donor [LURD] including 73 swap donor [SD] transplantations; 1294 males, 606 females; aged 36.3 ± 11.6 years, range 2-69 years).

TypeofStudy:Experience with Sandimmun/Sandimmun Neoral-based immunosuppression in living donor kidney transplantation performed between April 1984 and December 2002 at Yonsei University. Open study.

DosageDuration:Until 1997: Sandimmun 2 mg/kg iv initiated in the evening 2 days pretransplant, then 4 mg/kg daily iv, given bid, until 3 days posttransplant. Since 1998: oral Neoral was initiated in the immediate postoperative period. Duration: up to 10 years.

Results:The overall actuarial 10-year patient and graft survival rates were 80.8% (n=1535) and 60.8% (n=1155), respectively. The degree of HLA match did not impact graft survival in LURD transplant recipients. All SD transplant patients are alive with functioning graft (Neoral 73, tacrolimus 17). 507 patients lost their grafts due to patients' death (n=191), rejection (n=227; 203 chronic, 24 acute), recurrent disease (n=24), poor compliance (n=21), or other reasons. The incidence of early acute rejection during the follow-up period was 29.8% (n=285) and 38.7% (n=366) among related and unrelated kidney transplant recipients, respectively, with a statistically significant difference. Among the 507 patients, 213 died. The most common cause of death was infection (42.7%; n=91) followed by cardiovascular accidents (23.9%; n=51). Multivariate Cox regression analyses showed that risk factors affecting graft survival were donor and recipient age, degree of HLA match and occurrence of an acute rejection episode.

AdverseEffects:Infection occurred in 91 patients, malignancy in 19, causing death.

AuthorsConclusions:In summary, long-term graft survival has been markedly improved after the introduction of CsA [cyclosporin A] as the main immunosuppressant in living donor kidney transplantation at our institution. HLA-identical LRD kidney transplantation demonstrates the best long-term graft survival, but we could achieve good long-term graft survival in LURD kidney transplantation comparable to that of HLA-haploidentical LRD KTXs [kidney transplantations] using CsA as the main immunosuppressive agent.

FreeText:Between 1984-1997, patients received Sandimmun-based double-drug combination therapy as induction and maintenance immunosuppression. Since March 1995, all patients were switched from Sandimmun to Neoral . Since 1997, patients received triple-drug combination therapy including Neoral, mycophenolate mofetil 1-2 g daily and prednisone. Acute rejection episodes were first treated by high- dose methylprednislone pulse therapy. Steroid-resistant rejection was treated with antithymocyte globulin, antilymphocyte globulin or OKT3. After antirejection therapy, patients on double-drug therapy had azathioprine or mycophenolate mofetil added, and patients on triple-drug therapy had their Neoral or mycophenolate mofetil dose increased. Concomitant drugs: azathioprine, mycophenolate mofetil, prednisone, methylprednisolone (500 mg daily for 3 to 4 doses), 10-14 day course of antithymocyte globulin, antilymphocyte globulin, or OKT3. Whole blood Neoral trough levels were monitored by radioimmunoassay. Target blood trough levels were about 250 ng/mL and 150 ng/mL at 1 month and 1 year post-transplant, respectively. The diagnosis of rejection was based on the deterioration of graft function supplemented by Doppler ultrasound examination and/or graft biopsy.