ABSTRACT
INTRODUCTION: This study aimed to evaluate the effects of single nucleotide polymorphisms CYP3A4*1B and CYP3A5*3 on tacrolimus dose requirement among kidney transplant recipients. MATERIALS AND METHODS: Blood levels of tacrolimus were measured using microparticle enzyme immunoassay. Genotyping analysis utilized specific polymerase chain reaction-restriction fragment length polymorphism methods for 137 kidney transplant recipients. RESULTS: The median tacrolimus dose was significantly lower in the CYP3A4*1/*1 carriers (0.06 mg/kg/d; range, 0.007 mg/kg/d to 0.17 mg/kg/d) as compared to the CYP3A4*1B/*1B carriers (0.1 mg/kg/d; range, 0.03 mg/kg/d to 0.22 mg/kg/d; P = .001). Patients with at least 1 CYP3A5*1 wild-type allele required higher median doses of tacrolimus (median, 0.08 mg/kg/d; range, 0.03 mg/kg/d to 0.22 mg/kg/d) as compared to the CYP3A5*3 carriers (median, 0.05 mg/kg/d; range, 0.007 mg/kg/d to 0.17 mg/kg/d; P = .002). CONCLUSIONS: This study showed that tacrolimus dose requirement is lower in Jordanian kidney transplant recipients compared to other populations. Moreover, we found a correlation between genetic variations in CYP3A4 and CYP3A5 enzymes and tacrolimus blood levels among our kidney transplant recipients.
Subject(s)
Cytochrome P-450 CYP3A/genetics , Immunosuppressive Agents/administration & dosage , Kidney Transplantation , Polymorphism, Single Nucleotide/genetics , Tacrolimus/administration & dosage , Adult , Calcineurin Inhibitors/administration & dosage , Calcineurin Inhibitors/blood , Calcineurin Inhibitors/pharmacokinetics , Female , Genotype , Humans , Immunosuppressive Agents/blood , Immunosuppressive Agents/pharmacokinetics , Jordan/ethnology , Male , Polymorphism, Restriction Fragment Length/genetics , Tacrolimus/blood , Tacrolimus/pharmacokinetics , Transplant RecipientsABSTRACT
INTRODUCTION: The main objectives of this study were to estimate the prevalence of and the risk factors for the adverse effects of tacrolimus-based immunosuppression in patients who obtained renal transplant from living donors. METHODS: A multicenter cross-sectional observational study in 154 kidney transplant patients who received grafts from living donors. RESULTS: Large proportion of patients had hypertension (83%) and hyperlipidemia (53%); 27% had posttransplant diabetes mellitus. Patients had on average two chronic diseases. Tremor was present in 40%, neurologic toxicity in 45%, and anemia in 51.5% of patients. The average number of adverse effects was 3.52 ± 1.57. In multivariate analysis some adverse effects were related to tacrolimus concentration, duration of treatment, number of medications or medical problems. In linear regression analysis correlation was found, among the others, between diastolic blood pressure and tacrolimus concentration, and inverse correlation between erythrocyte count and duration of treatment. CONCLUSION: There is a significant prevalence of tacrolimus adverse effects and supratherapeutic TAC blood concentrations in Jordanian renal transplant patients in spite of using low TAC doses and overall adequate renal function.
