Long-term renal function in heart transplant recipients receiving cyclosporine therapy.

BACKGROUND: Immunosuppression with cyclosporine has improved allograft function and reduced both morbidity and mortality in organ transplantation. However, cyclosporine-induced nephrotoxicity still is a concern. The purpose of our study was to evaluate the effects of cyclosporine on renal function in orthotopic heart transplant recipients. METHODS: Thirty-nine patients who received transplants from 1985 to 1991 and had at least three yearly glomerular filtration rate measurements posttransplantation by 125I-iothalamate clearance method were included in the study. In addition, serum creatinine (before and after transplantation) and cyclosporine doses were analyzed. RESULTS: Maintenance immunosuppression at 1 year consisted of prednisone (0.1 mg/kg/day), azathioprine (2 mg/kg/day), and cyclosporine (12-hour trough level 100 to 150 ng/ml by fluorescence polarization immunoassay). The mean serum creatinine at 1 year was significantly higher than the mean pretransplantation serum creatinine (1.51 +/- 0.32 versus 1.28 +/- 0.38, p < 0.05) and stabilized after the first year. The mean glomerular filtration rate by 125I-iothalamate clearance method was 70.6 +/- 20.3 ml/min/1.73 m2 (range 32 to 105) at 1 year and remained relatively stable during the follow-up period of up to 7 years. Creatinine clearance calculated by the Cockcroft and Gault formula overestimated the true glomerular filtration rate after the third year. The mean cyclosporine dosage was significantly lower after the first-year dose of 3.9 +/- 1.8 mg/kg/day (p < 0.05). Three patients in 39 started hemodialysis at 5, 7, and 10 years after transplantation. CONCLUSION: Our data indicate that the adequacy of renal function is preserved with long-term cyclosporine therapy in heart transplant recipients.

Isoniazid hepatotoxicity in renal transplant recipients.

Tuberculosis occurs at higher rates in renal transplant recipients than in the general population. It would be desirable to use isoniazid prophylaxis in renal transplant recipients at risk for reactivation of tuberculosis; yet many transplant centers do not routinely employ INH prophylaxis because they perceive transplant recipients to be an enhanced risk of hepatotoxicity from isoniazid. Data on the risk of isoniazid in renal transplant patients receiving cyclosporine-based immunosuppression are limited. We retrospectively studied 83 renal transplant recipients (mean age 39.1 +/- 11.7 yr) who had received INH prophylaxis between 1985 and 1994. Eight patients had laboratory evidence of chronic hepatitis B or chronic hepatitis C infection. The mean duration of INH therapy was 344 +/- 163 d. The mean serum glutamate oxalacetic transferase (SGOT) at the start of INH therapy was 24.1 +/- 10.9 I.U., and 10% of patients had mildly elevated SGOTs. Mean peak SGOT during therapy was 36.4 +/- 15.3 I.U. (p < 0.001 compared to start (SGOT). In follow up, 31% of patients had an abnormal SGOT (> 40 I.U.); however, the elevations were small (the highest SGOT was 88.I.U.) and never necessitated discontinuation of INH. No patient had jaundice or other evidence of clinical hepatotoxicity. The 95% confidence interval for the observed frequency of clinical hepatitis was 0% to 4.3%. At the end of INH therapy the mean SGOT was 22.7 +/- 6.2 I.U. (p > 0.2, compared with start SGOT) and only one patient had an abnormal SGOT. In conclusion, it appears that the risk of renal transplant recipients developing serious hepatotoxicity with the administration of INH is low and not different from normal individuals.

Acyclovir prophylaxis for cytomegalovirus disease in high-risk renal transplant recipients: is it effective?

Cytomegalovirus (CMV) is a significant cause of post-transplantation morbidity and mortality in renal transplant recipients. The risk of CMV infection is between 60 to 88% in CMV seronegative patients who receive kidneys from CMV seropositive donors (D+, R-). In order to evaluate the efficacy of oral acyclovir in prevention of CMV infection after transplantation, we retrospectively reviewed the records of 25 patients (D+, R-) who were transplanted between January 1993 and December 1995. Eighteen of 25 patients received prophylaxis with variable doses of acyclovir (600 to 4000 mg/day, adjusted for their renal function) for 4 to 7 months. CMV disease was defined as fever (> or = 38 degrees C) for at least three days which could not be attributed to other causes with positive cultures or seroconversion for CMV, and presence of either leukopenia, pneumonitis, gastroenteritis or elevated liver enzymes. Twelve of the 18 patients (66.6%) who received acyclovir prophylaxis developed CMV disease. Seven patients were hospitalized and treated with i.v. ganciclovir. One patient died from CMV pneumonia associated with invasive fungal infection five months after transplantation. Of the 7 patients who did not receive prophylactic acyclovir, 5 (71.4%) developed CMV disease (2 patients were hospitalized and treated with ganciclovir). Our results failed to confirm the efficacy of oral acyclovir as a prophylaxis against CMV disease in a small group of high-risk patients. We conclude that other strategies should be tested.