Effect of grapefruit juice on cyclosporin A pharmacokinetics in pediatric renal transplant patients.

Cyclosporin A (CsA) is an important immunosuppressant that is prone to numerous drug interactions. Grapefruit juice has been investigated, as a possible adjunct to CsA dosing in adult renal transplant recipients, to decrease CsA metabolism and reduce dosages. This study investigated this combination in pediatric renal transplant patients. Six stable pediatric renal transplant patients were entered into an open-label, four-period cross-over study in which patients were given their current CsA dose as either an oral solution (CsA-Sol) or a microemulsion (CsA-ME). In addition, drugs were administered concurrently with water or grapefruit juice. Steady-state pharmacokinetic profiles were taken during each of the four periods. Following the concurrent administration of grapefruit juice, CsA whole-blood 12-h trough levels were significantly increased during CsA-Sol dosing. Furthermore, the CsA elimination rate constant was significantly reduced during the same period. After CsA-ME dosing, no differences in CsA pharmacokinetics were found between concurrent water or grapefruit ingestion. Grapefruit juice co-administration reduced the production of CsA metabolites, AM1 and AM9, during CsA-Sol dosing. No changes in CsA metabolite production were found when patients were given CsA-ME with grapefruit juice as compared with water. Hence, alterations in CsA absorption and elimination occur with concurrent grapefruit juice ingestion when stable pediatric renal transplant patients are taking the oral CsA solution, but not the microemulsion formulation. These changes may be mediated by alterations in intestinal or hepatic metabolism, or drug absorption. The effect of grapefruit juice on CsA absorption is not readily predictable in these patients.

Kidney transplantation in children: a single center experience.

PURPOSE: We reviewed our most recent 10-year experience with kidney transplantation in children to determine the morbidity and mortality of the procedure, and to identify factors that affected outcome. MATERIALS AND METHODS: A total of 107 renal transplants were done in 95 children 1 to 17 years old (mean age 10.9) during the 10-year period ending January 1, 1997. The 4 most common causes of end stage renal disease were renal dysplasia, reflux nephropathy, obstructive uropathy and systemic immunological diseases. Cyclosporine based immunosuppression was used in all but 2 recipients. After April 1991 antilymphocyte antibody induction, coagulopathy screening, systemic anticoagulation and cytomegalovirus prophylaxis were incorporated into the protocols. The effects of kidney source, recipient gender, recipient age, preformed anti-HLA antibody level, preemptive renal transplantation, cytomegalovirus risk, antilymphocyte antibody induction therapy and date of renal transplantation on kidney graft survival were examined with the log rank test. RESULTS: The 1-year graft and patient survival rates were 91 and 99%, respectively. The most common causes of graft failure were rejection and recurrence of primary renal disease. The only factors that significantly (p < 0.05) influenced graft survival were antilymphocyte antibody induction immunosuppression and kidney transplantation after April 1991. Three urological complications required surgical correction. Medical morbidity included hypertension in 48.6% of the cases, short stature in 46.6% and obesity in 58.9%. CONCLUSIONS: Pediatric renal transplantation can be done with acceptable morbidity, a low rate of technical complications and low mortality. Hypertension, chronic rejection and abnormal body habitus continue to be problematic.

Immune complex disease associated with Epstein-Barr virus infectious mononucleosis.

We describe a patient with immune complex-mediated glomerulonephritis and leukocytoclastic vasculitis associated with Epstein-Barr virus (EBV) infectious mononucleosis. The patient required hemodialysis and has residual hypertension. This case implicates acute EBV infection as a cause of immune complex-mediated glomerulonephritis.

Cyclosporine in glomerular disease.

Cyclosporine was introduced in 1981 as an immunosuppressive agent in renal transplantation. Its use was soon extended to the treatment of various glomerular disorders. In light of its known immunomodulating effects, the use of cyclosporine has been most prominent in those glomerular diseases thought to have an immune basis. The most careful studies of cyclosporine in glomerular diseases have been performed in the pediatric population with idiopathic nephrotic syndrome (i.e., minimal change disease and focal segmental glomerulosclerosis), although data are accumulating regarding efficacy and safety in adults with idiopathic nephrotic syndrome. In patients who are steroid-dependent, cyclosporine therapy can induce complete or partial remission in a significant proportion of cases; success rates in patients with steroid-resistant nephrotic syndrome are less encouraging. Treatment with cyclosporine allows for dose reduction or elimination of corticosteroids, and the consequent salutary effect on growth in the child and glucose and bone metabolism in all patients. Studies that suggest a potential benefit of cyclosporine in recurrent nephrotic syndrome in renal allografts and in other glomerular diseases are also discussed.