ABSTRACT
BACKGROUND: The major immunosuppressive effect of cyclosporine is through the inhibition of calcineurin, an enzyme important in the activation of T lymphocytes. In children, neither calcineurin activity nor its inhibition by cyclosporine (CsA) has been investigated. METHODS: Calcineurin activity, was measured in stable pediatric renal transplant patients, with healthy children used as controls. Whole blood CsA concentrations were measured by monoclonal radioimmunoassay. Simultaneous calcineurin and CsA levels were measured before and 1, 2, 3.5, 5, and 12 hr after their routine morning CsA dose. RESULTS: Calcineurin activity was approximately 50% inhibited at trough blood concentrations (148 microg/L); moreover, inhibition increased as CsA concentrations rose and declined as concentrations fell. Maximum calcineurin inhibition was about 70% at concentrations of about 431 microg/L. Linear regression analysis revealed a significant correlation between mean CsA blood concentration and the mean degree of inhibition of calcineurin activity (P=0.005, one-tailed). CONCLUSION: We conclude that inhibition of calcineurin activity by CsA in pediatric renal transplant recipients correlates with CsA blood concentrations.
Subject(s)
Calcineurin/metabolism , Cyclosporine/therapeutic use , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Adolescent , Adult , Calcineurin Inhibitors , Child , Cyclosporine/blood , Cyclosporine/pharmacology , Humans , Immunosuppressive Agents/blood , Immunosuppressive Agents/pharmacology , Lymphocyte Activation/drug effects , T-Lymphocytes/immunologyABSTRACT
Varicella vaccine was administered to seven children with corticosteroid-sensitive nephrotic syndrome. Immunization was not associated with any significant reactions or with increased frequency of relapse. The antibody response was, however, variable and a second dose was necessary before seroconversion was achieved in four patients. The findings indicate that immunization with varicella vaccine is safe in children with nephrotic syndrome in remission, but that a two-dose vaccine schedule should be considered.
Subject(s)
Chickenpox Vaccine , Chickenpox/prevention & control , Nephrotic Syndrome/immunology , Antibodies, Viral/biosynthesis , Chickenpox/immunology , Child , Child, Preschool , Dose-Response Relationship, Drug , Follow-Up Studies , Humans , Immunization Schedule , Remission, SpontaneousABSTRACT
A retrospective review was conducted to determine the incidence, etiology, natural history and complications of hyperuricemia after pediatric renal transplantation. Of 81 active transplant recipients aged 10.1 +/- 4.8 (mean +/- SD) years being followed by St. Christopher's Hospital for Children, 57 (70%) were males and 59 (73%) Caucasian. Their immunosuppression consisted of azathioprine, cyclosporine A and prednisone. Mean serum uric acid concentrations peaked at 6 months post transplantation (6.2 +/- 2.6 mg/dl), when 39% of the patients had hyperuricemia and 60% were receiving diuretics, and decreased thereafter. At 30 months, 23% of the patients had hyperuricemia and 17% required diuretics. When we compared 42 normouricemic (group A) with 24 hyperuricemic (group B) patients at 18 months post transplantation, we found that patients in group B were older (11.6 +/- 4.2 vs. 8.6 +/- 5.2 years, P = 0.01), had worse renal function (77 +/- 25 vs. 96 +/- 36 ml/min per 1.73 m2, P = 0.03) and required diuretics more frequently (63% vs. 21%, P = 0.001), but had identical blood levels of cyclosporine A (82 +/- 28 vs. 84 +/- 35 ng/ml, P = 0.78). A family history of gout did not affect the prevalence of hyperuricemia after transplantation. Asymptomatic hyperuricemia is common following pediatric renal transplantation and is more likely attributable to reduced renal function and diuretic therapy than to the known hyperuricemic effect of cyclosporine A. Of these variables, only diuretic therapy is readily controllable and should be closely regulated following pediatric renal transplantation.
