title: Correlation of C0 and C2 levels with cyclosporine side effects in kidney transplantation.
abstract: Cyclosporine has a narrow therapeutic window requiring close monitoring to ensure adequate immunosuppression while avoiding nephrotoxicity and other side effects. Pharmacokinetic studies have suggested that cyclosporine levels at 2 hours postdose (C2) is the best single time point to predict area under the concentration curve (AUC) in kidney transplant recipients. C2 also predicted acute rejection episodes and nephrotoxicity better than trough levels (C0). Targeting cyclosporine levels to minimize side effects while maintaining adequate immunosuppressive effects is of clinical interest. There are conflicting evidence and few reports about whether cyclosporine-related side effects are a dose-dependent phenomenon. The aim of this single center study was to ascertain whether cyclosporine side effects were dose-dependent and which single time point level (C0 or C2) was more closely related to them. We analyzed 225 patients on Neoral-based immunosuppression with C0 and C2 levels measured on the same day of 2 different visits. Serum creatinine, glucose, uric acid, potassium, total cholesterol, triglycerides, and 24-hour urinary sodium elimination were measured by routine biochemical analyses. Blood pressure was measured at each visit. A significant positive correlation was observed between C2 and C0 concentrations and levels of potassium (P < .001), total cholesterol (P < .001), systolic blood pressure (P < .001), and pulse pressure (P < .01). There was a significant negative correlation between C2 and uric acid (P < .001). AUCs of receiver operating characteristic (ROC) curves for both C2 and C0 levels were significant as predictors of hyperkalemia (P < .001), hyperuricemia (P = .001), hypercholesterolemia (P < .05), and high systolic blood pressure (P < .05). There were no significant differences between the capacities of C2 or C0 to predict these variables. In conclusion, potassium, total cholesterol, uric acid, and systolic hypertension were influenced by cyclosporine in a dose-dependent manner. Both C2 and C0 were useful to predict cyclosporine side effects.
authors.affiliation: Service of Nephrology, Hospital Valdecilla, University of Cantabria, Santander, Spain. nefrce@humv.es
authors.forename: E
authors.initials: E
authors.lastname: Rodrigo
authors.forename: J C
authors.initials: JC
authors.lastname: Ruiz
authors.forename: M
authors.initials: M
authors.lastname: Angeles de Cos
authors.forename: J
authors.initials: J
authors.lastname: Ruiz
authors.forename: M
authors.initials: M
authors.lastname: Gago
authors.forename: C
authors.initials: C
authors.lastname: Piñera
authors.forename: B
authors.initials: B
authors.lastname: Sánchez
authors.forename: J
authors.initials: J
authors.lastname: González-Cotorruelo
authors.forename: C
authors.initials: C
authors.lastname: Gómez-Alamillo
authors.forename: M
authors.initials: M
authors.lastname: Arias
mesh_terms: D019540:Area Under Curve; D001794:Blood Pressure; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000378:metabolism; D016572:Cyclosporine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017248:Enzyme Multiplied Immunoassay Technique; D006084:Graft Rejection / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology*; D011188:Potassium / Q000097:blood; D011674:Pulse; D012372:ROC Curve; D012189:Retrospective Studies; D012964:Sodium / Q000652:urine; D014527:Uric Acid / Q000652:urine
chemical_list: D007166:Immunosuppressive Agents; D014527:Uric Acid; D016572:Cyclosporine; D002784:Cholesterol; D012964:Sodium; D003404:Creatinine; D011188:Potassium