ABSTRACT
Background: Tacrolimus is a widely used immunosuppressant that prevents solid organ transplant rejection. The pharmacokinetics of Tacrolimus show considerable varia - bility. Interleukin-10 (IL-10), in the host's immune response after transplantation, contributes to the variable CYP3Adependent drug disposition of Tacrolimus. In the current study, we aim to evaluate the impact of single nucleotide polymorphisms (SNP) in the promoter region of IL-10 on Tacrolimus dose requirements and the Dose Adjusted Concentration (DAC) of Tacrolimus among kidney transplantation recipients. Methods: Blood levels of Tacrolimus were measured using Microparticle Enzyme Immunoassay (MEIA) for six months post-transplantation. Genotyping analysis was utilized using specific Polymerase Chain Reaction (PCR) followed by sequencing methods for 98 Jordanian kidney transplant recipients. Results: Genotyping frequencies of IL-10 (-592) were (CC/CA/AA: 38, 46.7, 15.2%); IL-10 (-819) were (CC/CT/TT: 40.4, 44.1, 15.1%); and IL-10 (-1082) were (AA/AG/GG: 42.6, 44.7, 12.8%). The impact of IL-10 (-1082) on Tacrolimus DAC was gender dependent. Men carrying at least one A allele had significantly lower DAC than men carrying GG genotyping only in the first month post-transplantation 88.2±32.1 vs. 117.5±22.5 ng/mL per mg/kg/day, p=0.04 . Conclusions: Our current study showed that the interaction between gender and IL-10 -1082 affects Tacrolimus DAC in Jordanian kidney transplant recipients during the first month post-transplantation.
ABSTRACT
BACKGROUND: Hypertension affects 70-90 % of all kidney transplant recipients. It is associated with poor graft survival and is a contributing factor to the increased cardiovascular mortality. The reasons for the insufficient blood pressure control in transplanted patients have not been thoroughly investigated. OBJECTIVE: To evaluate the extent of blood pressure control in Jordanian hypertensive renal transplant recipients and to assess factors associated with such control. SETTING: Three outpatient renal transplant clinics in Amman. METHOD: A cross-sectional observational study including 181 patients. We have considered blood pressure <130/80 mm Hg as controlled hypertension. Bivariate and multivariate logistic regression analyses were used to determine clinical factors associated with achievement of blood pressure control. MAIN OUTCOME MEASURES: Proportion of patients who achieved hypertension control and clinical factors associated with good blood pressure control. RESULTS: Mean systolic blood pressure was 128.6 ± 16.3 mm Hg and mean diastolic blood pressure was 82.8 ± 11.5 mm Hg. Blood pressure control was achieved only in 58 % of patients. The most commonly prescribed antihypertensives were calcium channel blockers (58 %) followed by beta-blockers (44 %). In bivariate analysis, female gender (p = 0.017) and creatinine clearance (p = 0.002) were positively associated, while number of antihypertensive medications was inversely associated (p = 0.04) with achievement of blood pressure control. After including these factors in multivariate logistic regression analysis, only creatinine clearance remained independently associated with hypertension control (odds ratio, OR 1.04; 95 % confidence interval [CI] 1.01-1.06; p = 0.003). CONCLUSION: Blood pressure control among renal transplant recipients in Jordan was found to be inadequate. The only factor found to be independently associated with adequate blood pressure control was creatinine clearance.
