Improved results of cadaver renal transplantation with azathioprine, prednisone and antilymphoblast globulin

From 1980 to 1982, 100 consecutive cadaver renal transplants were performed. All but 2 recipients received preoperative transfusion and all received an initial 2-week course of antilymphoblast globulin. A prospective controlled evaluation of high versus low maintenance prednisone, and antilymphoblast globulin versus intravenous methylprednisolone for first rejection therapy was done. Over-all 1-year graft and patient survivals were 77 and 96 per cent, respectively. Graft survival was equal in the high and low steroid groups. Antilymphoblast globulin was as effective as intravenous methylprednisolone in reversing first rejections. Graft survival was improved with better donor-recipient matched grafts. We conclude that excellent results can be obtained in transfused cadaver renal allograft recipients managed with azathioprine, prednisone and antilymphoblast globulin. The regimen of prophylactic antilymphoblast globulin, low maintenance prednisone and antilymphoblast globulin alone for first rejections is immunologically effective and steroid sparing.     

Testicular function after renal transplantation: comparison of Cyclosporin A with azathioprine and prednisone combination regimes

Testicular function was assessed in 24 men after renal transplantation who were on either Cyclosporin A (CSA) (8 men) or a combination of azathioprine and prednisone (AZP) (16 men) as immunosuppressive therapy. The different regimes were not associated with any differences in clinical or hormonal (LH, FSH, prolactin, testosterone, estradiol) indices of testicular function although adrenal androgen (dehydroepiandrosterone sulphate) was suppressed in prednisone-treated men. Overall, however, poor graft function was associated with abnormal testicular function. Renal allograft function rather than immunosuppressive regime was the major determinant of gonadal function.     

The effects of a maintenance immunosuppressive protocol after renal transplantation on infectious complications, comparing cyclosporine/prednisone, cyclosporine/azathioprine/prednisone, and conversion

Infectious complications of either high-dose (16 mg/kg/day) or low-dose (9 mg/kg/day) cyclosporine in combination with azathioprine (Aza) (1 mg/kg/day) were studied in 128 renal transplant patients who also received low-dose prednisone (P). Three months after transplantation all patients were again randomly assigned to either continuation with CsA/P or conversion to Aza/P. During the first 3 months the number of infections was significantly lower in the CsA/P treatment than in the CsA/Aza/P group. In both groups the number of infections doubled after rejection treatment. The frequence of symptomatic CMV disease did not differ between the 2 groups. Three months after transplantation, the patient group assigned to Aza/P had a small but not significant increase of minor infections when compared with the patients who continued with CsA/P. The number of major infections did not differ between these two groups.     

肾移植术后他克莫司加泼尼松二联免疫抑制治疗的临床观察

目的：探讨肾移植术后他克莫司（FK506）加泼尼松（Pred)二联免疫抑制治疗方案的临床疗效及副作用。方法：22例尸肾移植患者术后应用FK506加Pred二联免疫抑制治疗，临床观察3－22个月，监测FK506血浓度和副作用及移植肾功能。结果：22例患者术后肾功能均恢复正常，无排斥反应，FK506血浓度手术后第1个月为10－15μg/L，第2－3个月为8－10μg/L,3个月后浓度维持在5－9μg/L即可。22例中，仅1例于术后3个月发生糖尿病，现口服降糖药。血糖控制在正常范围。结论：肾移植术后FK506加Pred二联免疫抑制治疗方案是安全和有效的。     

Treatment of renal transplant rejection episodes in patients receiving prednisone and azathioprine. A cost-effective approach

Antilymphocyte globulin (ALG) has been advocated for the treatment of renal transplant rejection episodes in patients maintained on prednisone and azathioprine. Treatment with steroids (outpatient) is considerably less expensive than with ALG (inpatient), so we studied whether routine ALG was necessary. Between 3/82 and 11/83, 54 cadaver transplant recipients maintained on prednisone and azathioprine who developed a first rejection episode were randomized to receive--for treatment of their first, and if necessary second, rejection--methylprednisolone (MP) plus ALG (n = 24), or MP alone, with ALG added if treatment failed (n = 30). Treatment failure was defined as continuing deterioration on T131 iodohippuran scan, rising serum creatinine level, or lack of improvement within 7 days. There was no significant difference in patient survival, graft survival, mean number of rejections, and infection rate between the two groups: 60% (18/30) of first and 50% (10/10) of second rejection episodes responded to MP alone. We conclude that patients are not penalized by initial rejection treatment with MP. Many rejection episodes respond to steroids alone; elimination of routine ALG use will save hospitalization time and expense.     

Results of conversion from cyclosporine to azathioprine in cadaveric renal transplantation

Between December 1983 and August 1985, 110 cadaver transplants were performed at our institution. All were started on cyclosporine (CsA) and prednisone (P) for immunosuppressive therapy. Of the 110 patients, 46 were converted from CsA to azathioprine (AZA) for a variety of reasons (cost, toxicity, patient preference, prolonged dysfunction posttransplant, or nonresponsive rejection). The course and outcome of these patients are described. The only group of patients who had consistent benefit and stable course following the CsA-to-AZA switch were primary cadaver transplants with stable renal function (serum creatinine less than 2 mg/dl) who were converted an average of 7.97 months posttransplant. All other groups of patients had severe problems or graft loss postconversion.     

Beneficial effects of cyclosporine compared with azathioprine in cadaveric renal transplantation

Recent reports have intimated that the use of antilymphocyte globulin in combination with azathioprine and steroids has ameliorated the beneficial affects of cyclosporine. We believe that even in the absence of significant statistical differences between patient survival rates and graft survival rates of cyclosporine-treated renal transplant patients compared with conventionally treated renal transplant patients, there are distinct advantages to cyclosporine use in renal transplantation. Twenty-three consecutive cadaveric renal transplant patients who received azathioprine, prednisone, and antilymphoblast globulin were compared with 23 cadaveric renal transplant patients who received cyclosporine and prednisone. Fewer statistically significant rejection episodes, multiple rejection episodes, and cytomegalovirus infections were demonstrated in those who received cyclosporine. Most notably, cyclosporine decreased the initial hospital stay, was associated with fewer readmissions, and therefore markedly reduced the initial cost of transplantation.     

Sequential antilymphoblast globulin and cyclosporine for renal transplantation

The nephrotoxic effects of cyclosporine (CsA) seem to be augmented by co-existing renal injury. A high rate of prolonged delayed function (acute tubular necrosis [ATN]) and non-function (NF) has been associated with the use of CsA prior to and following renal transplantation. Cyclosporine has also been associated with a slower recovery of allograft function and poor baseline renal function even in allografts that function immediately compared with conventionally treated recipients. In 1983 we hypothesized that the rate of ATN and NF following renal transplantation could be decreased and more normal kidney function achieved if renal injury was resolved before adding the nephrotoxic effects of CsA. A group of 300 nonsplenectomized, uremic recipients have received 304 renal transplants and have been initially immunosuppressed with azathioprine, prednisone, and Minnesota antilymphoblast globulin (ALG) prior to starting maintenance CsA and prednisone. The incidence of NF has been 1.9% and the development of ATN has been 7.6% following transplantation with sequential use of ALG and CsA. Other benefits to the renal recipient have also occurred with use of this immunotherapy protocol. Renal allograft survival for recipients of first, second, and third renal allografts has been higher than that generally reported with cyclosporine and prednisone alone. Rejection episodes have been infrequent during the first six months posttransplant, as 75% and 62% of first and second renal allograft recipients have remained rejection-free. Clinically significant infectious complications were infrequent. No cadaver recipient has developed a lymphoma. Moreover, the initial hospitalization following transplantation with sequential ALG/CsA has been short and generally uncomplicated. We conclude that sequential ALG/CsA following renal transplantation provides excellent early posttransplant immunosuppression while avoiding the nephrotoxic effects of CsA and also provides the steroid and infection-sparing benefits derived from maintenance CsA therapy.     

Safe conversion from cyclosporine to azathioprine with improved renal function in pediatric renal transplantation

Although cyclosporine has improved allograft survival in renal transplant patients, problems with drug toxicity remain, raising the question whether cyclosporine should be stopped at some point post-transplant. However, the relative safety of converting from cyclosporine to another immunosuppressive agent, or simply stopping cyclosporine remains an issue of debate and has not been evaluated in children. We have developed a protocol to convert children, who are 6 months post-transplant and have stable kidney function, from cyclosporine and prednisone to azathioprine and prednisone. Eleven children have undergone conversion because of suspected/potential nephrotoxicity or because of other difficulties with cyclosporine (expense, hirsutism). These children were compared with a control group of 12 children who met all criteria for conversion at 6 months but remained on cyclosporine. Allograft survival was similar in both groups but the children converted from cyclosporine experienced an improvement in renal function as measured by calculated creatinine clearance. There were no episodes of rejection for a period of 4 months postconversion and all rejection episodes that developed subsequently occurred during or after the change from daily to alternate-day prednisone. We believe that conversion from cyclosporine to azathioprine can be accomplished safely in children with stable allograft function but long-term risks and benefits need further evaluation.     

Cyclosporine alone or in combination with prednisone in cadaveric renal transplantation

One hundred recipients of first cadaveric kidney transplants were treated with three different immunosuppressive regimens: (1) conventional immunosuppression, (2) CsA alone, and (3) low-dose CsA in combination with low-dose prednisone, with rapid adjustment to give CsA whole blood trough levels of 300 to 800 ng/mL. One-year graft survival in the aza + pred group was 76%, and in the CsA alone group 75%. Graft survival at two and six months in the CsA-pred group was 94%. The dose of CsA in the CsA-pred group in the first two months posttransplant was only about half that given to the CsA-alone group. Surprisingly, the reduction in the CsA dose also reduced the number of methylprednisolone pulses given for treating rejection by greater than 50%. The incidence of nephrotoxicity and extrarenal side effects also fell considerably. Withdrawal of prednisone in the CsA-pred group after five months led to reversible rejection in two cases. In conclusion, (1) the rapid reduction in the CsA dosage is beneficial and has no drawbacks, and (2) our guidelines for withdrawing prednisone (timing of withdrawal, rate of reduction in dosage) still need further refinement.     

Rapid discontinuation of prednisone in higher-risk kidney transplant recipients

Prednisone-minimization protocols have been successful in low-risk recipients. We report on the use of a protocol incorporating rapid discontinuation of prednisone in a cohort of kidney transplant recipients (n = 79) at increased immunologic risk. Our data suggests that such recipients should not be excluded from prednisone-minimization protocols.     

Immunosuppression with azathioprine, prednisone, and cyclophosphamide.

An immunosuppressive regimen consisting of azathioprine (AZ), prednisone, and intermittent i.v. infusions of 400 mg of cyclophosphamide (CY) in the first post-transplant month was prospectively compared with a no CY regimen. There were no significant differences in patient or graft survival, graft function, or infectious complications between the two regimens.