Başkent Üniversitesi Yayınları

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    Mycophenolic Acid Pharmacokinetics Early After Kidney Transplant
    (Başkent Üniversitesi, 2013-04) Honarbakhsh, Nazanin; Gholami, Kheirollah; Mohebbi, Niayesh; Javadi, Mohammad Reza; Lesan-Pezeshki, Mahboob; Rouini, Mohammad Reza; Karimzadeh, Iman
    Objectives: To determine the mycophenolic acid pharmacokinetic profile early after transplant in Iranian kidney graft recipients. Materials and Methods: A cross-sectional study was performed during 6 months in 31 patients who recently had kidney transplant and received fixed doses of mycophenolate mofetil (2 g/d). The plasma levels of mycophenolic acid were determined by high performance liquid chromatography. Results: The mean first mycophenolic acid peak level was 10 ± 5 mg/L. The mean mycophenolic acid area under the curve was 26 ± 19 mgh/L and apparent clearance was 57 ± 55 L/h. The mycophenolic acid area under the curve values of only 8 patients (26%) were within the therapeutic range (30-60 mgh/L). The first, second, and third mycophenolic acid peak levels correlated significantly with mycophenolic acid area under the curve (P < .05). Mycophenolic acid concentration at 10 hours had the highest correlation with mycophenolic acid area under the curve (r=0.962; P < .05). No statistically significant differences were evident in the mean mycophenolic acid area under the curve between men and women. Conclusions: There was a high degree of variation between different patients in mycophenolic acid pharmacokinetics early after kidney transplant.
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    Influence of Endothelial Nitric Oxide Synthase Gene Polymorphisms (-786T/C, 4a4b, 894G/T) on Iranian Kidney Transplant Recipients
    (Başkent Üniversitesi, 2013-02) Azarpira, Negar; Ayatolahi, Maryam; Darai, Masumeh; Bahador, Ali; Geramizadeh, Bita; Aghdai, Mahdokht H.
    Objectives: Nitric oxide is a major mediator in vascular biology and regulator of regional blood flow. Its production is catalyzed by the enzyme endothelial nitric oxide synthase. Protective actions of nitric oxide in ischemia and reperfusion are due to its potential as an antioxidant and anti-inflammatory agent, along with its inhibitory effects on cell signaling pathways of nuclear proteins, such as NF-κB. The endothelial nitric oxide synthase gene polymorphisms affect endothelial nitric oxide synthase activity and are associated with endothelial dysfunction. This study sought to examine the association between single nucleotide polymorphisms in endothelial nitric oxide synthase gene (rs 2070744, 27VNTR, and rs1799983) and the development of acute rejection in renal transplant patients. Materials and Methods: Sixty-six renal transplant recipients (33 patients with an episode of acute rejection and 33 recipients an episode of acute rejection), between June 2010 and March 2011, were included. The polymorphism was determined by simple polymerase chain reaction and polymerase chain reaction-restriction fragment-length polymorphism analysis. Results: There was only a significant association of endothelial nitric oxide synthase -786T allele and acute rejection (P = .03). Recessive model of T-786C alleles (TT vs TC+CC) and acute rejection confirmed a significant association (odds ratio: 3.12; 95% CI: 0.01-9.83; P = .025). Haplotype CbG was higher in recipients without rejection as compared to rejection group (OR: 0.42, 95% CI: 0.16-1.13; P < .05). Respecting the endothelial nitric oxide synthase gene 894G/T single nucleotide polymorphisms and 27VNTR, no significant association between the allele/genotype and acute rejection was seen. Conclusion: Recipient endothelial nitric oxide synthase gene polymorphisms do not alter the risk of acute rejection after a renal transplant. Rejection is a complex immunologic event. Therefore, finding associated genetic variants demands a multicentric larger sample size.
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    Early Allograft Biopsies Performed During Delayed Graft Function May Not Be Necessary Under Thymoglobulin Induction
    (Başkent Üniversitesi, 2012-06) Ortiz, Jorge; Chewaproug, Daranee; Balasubramanian, Manju; Zaki, Radi; Campos, Stalin; Feyssa, Eyob; Khanmoradi, Kamran; Mumtaz, Khurram; Parsikia, Afshin
    Objectives: Delayed graft function affects up to 50% of kidney transplant recipients. Some guidelines recommend surveillance biopsies beginning 7 days after engraftment. This may be unnecessary with anti-thymocyte globulin induction. Materials and Methods: We conducted a retrospective study of deceased-donor renal transplant recipients with delayed graft function. Results: One hundred eleven patients met the inclusion criteria. The incidence of rejections during delayed graft function was 2.7%. They were diagnosed between 9 and 11 days after transplant. The subsequent incidence of rejection at 12-month follow-up was 13.5% (n=15). The median time to rejection after transplant was 10 weeks. Fourteen of 15 patients had subtherapeutic immuno­suppression. The only risk factor associated with later rejection after delayed graft function was use of donors after cardiac death. Conclusions: Early rejection during delayed graft function with anti-thymocyte globulin induction and maintenance immunosuppression with tacrolimus, mycophenolate mofetil, and steroids is rare. When later rejection occurs, it is at a median of 10 weeks after a transplant. Two of the 3 early rejections were antibody mediated. Later rejections were associated with subtherapeutic immunosuppression and donors after cardiac death. Biopsies need not be performed during the early postoperative period when anti-thymocyte globulin is used with tacrolimus, mycophenolate mofetil, and steroids.