Başkent Üniversitesi Makaleler

Permanent URI for this collectionhttps://hdl.handle.net/11727/13096

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search.filters.applied.f.language: search.filters.language.enSubject: search.filters.subject.Kidney transplantation

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    Association between Cyclosporine Concentration and Genetic Polymorphisms of CYP3A5 and MDR1 during the Early Stage after Renal Transplantation
    (Başkent Üniversitesi, 2006-06) Azarpira, N.; Aghdaie, MH.; Behzad-Behbahanie, A.; Geramizadeh, B.; Behzadi, S.; Malekhoseinie, SA .; Raisjalal, GH.; Rahsaz, M.; Pourgholami, A.; Sagheb, F.
    Objectives: Cyclosporine (CsA) has a narrow therapeutic range, and its pharmacokinetic characteristics vary among individuals. It also is a substrate for cytochrome P450 (CYP) 3A and P-glycoprotein, the product of the multidrug resistance 1 (MDR1) and CYP3A5 genes. Some of the single nucleotide polymorphisms (SNPs) in these genes are associated with deficient protein expression and reduced in vivo activity. We postulated that in renal transplant recipients, these SNPs should be associated with interindividual variations in CsA pharmacokinetics. Materials and Methods: In 88 Iranian renal transplant patients receiving CsA, CYP3A5 and MDR1 genotypes were determined by polymerase chain reaction, followed by restriction fragment length polymorphism analysis. Whole blood trough CsA concentrations were measured by radioactive immunosorbent assay. The dose-adjusted concentration (ng/mL per mg/kg/d) was calculated at 1 day (± 2 days), 7 days, and 1 month after transplantation. Results: The MDR-1 wild-type genotype (3435CC) was observed in 17 patients (19%), whereas 45 patients (51%) were heterozygous (3435CT), and 26 patients (30%) were homozygous (3435 TT) for the mutation. In the days immediately after transplantation, we found a correlation between the concentration/dose ratio and the exon 26 MDR single nucleotide polymorphisms (33.3 ± 15.24 µg mg/L/kg in the CT group vs 44.1 ± 28.4 µg mg/L/kg in the TT group, P = .019). This ratio was significantly higher in subjects homozygous for the mutation (3435TT). This significant difference was not seen 1 week or 1 month after transplantation. All patients had the CYP3A5*3/*3 genotype, so no differences among the CYP3A5*1/*3 genotypes were found. Conclusions: MDR-1 (3435CC) polymorphisms are associated with CsA pharmacokinetics and dose requirements in the first few days after renal transplantation. Pharmacogenetic methods could be used to help select the initial dosage and individualize immunosuppressive therapy. According to our results, the major genotype of our recipients is CYP3A5*3/*3. According to the literature, the recommended starting dosage of CsA is 9-14 mg/kg/day; however, the Iranian population has a good response with lower dosages (3-5 mg/kg/day), which may be explained by genetic differences.
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    ABO Incompatible Kidney Transplantation -Immunological Aspect-
    (Başkent Üniversitesi, 2003-12) Aikawa, Atsushi; Yamashita, Mioko; Hadano, Tomomi; Ohara, Takehiro; Arai, Kenji; Kawamura, Takeshi; Hasegawa, Akira
    ABO incompatible kidney transplantation (ABOINCKT) has been developed in Japan because of the shortage of cadaveric donors. We have performed 76 living-donor ABOINCKT in our center. Donor blood type antibody was removed by immunoadsorption or plasmapheresis and exchange. Immunosuppression consisted of cyclosporine or tacrolimus, steroid, and cyclophosphamide or azathioprine or mycophenolate mofetil and, recently, basiliximab. Splenectomy was routinely performed during the transplantation surgery. Donor blood type antigen was strongly expressed on the vascular endothelium at all time points and in all conditions posttransplantation. Red blood cell agglutination reaction (RBAR) was positive only in renal tissues from a patient with delayed hyperacute rejection. Donor specific antibody suppression was observed in 18 ABOINCKT recipients with blood type O from a donor with blood type A1 or B. ADCC activity was detected after pre-treatment. Acute humoral rejection in ABOINCKT can result from ADCC, as well as by antigen-antibody reaction. Five year graft and patient survival rates were 75% and 64% in 37 ABOINCKT recipients from June 1989 through December 1996, however they have been 100% in 39 ABOINCKT recipients since January 1997. Accommodation has been produced in ABOINCKT with the co-existence of blood type antigen and antibody. Currently, ABOINCKT is an alternative which should be considered, particularly for blood type O patients with extended waits for cadaveric transplantation and for pediatric patients.