This is the first study to extensively determine the effect of CYP3A4*1G and CYP3A5*3 genetic polymorphisms and hematocrit value on tacrolimus pharmacokinetics in Chinese renal transplant recipients. The findings suggest that CYP3A5*3 and CYP3A4*1G polymorphisms and hematocrit are determinant factors in the apparent clearance of tacrolimus. The initial dose design is mainly based on CYP3A5 and CYP3A4 genotypes as well as hematocrit. This result may also be useful for maintenance tacrolimus dose optimization and may help to avoid fluctuating tacrolimus levels and improve the efficacy and tolerability of tacrolimus in kidney transplant recipients.
New Onset Diabetes after Transplantation (NODAT) is defined as sustained hyperglycemia developing in patients without diabetes history before transplantation. A cohort study was performed to access the effects of tacrolimus on insulin secretion and insulin sensitivity and consequently in the development of NODAT in kidney transplant recipients. Then, we further investigated the association between NODAT and single-nucleotide polymorphisms of IRS-1 and IRS-2 in renal allograft recipients. One hundred and fifty-eight kidney transplant patients, receiving tacrolimus as the base immunosuppressant, were divided into two groups: with or without NODAT. Plasma levels of fasting insulin concentration (FINS) and C-peptide were determined by enhanced chemiluminescence immunoassay and ADVIA Centaur C peptide assay, respectively. The genotypes of Gly1057Asp in IRS-2 and Gly972Arg in IRS-1 were detected through polymerase chain reaction fragment length polymorphism in NODAT and non-NODAT patients. It was found that the concentrations of fasting plasma insulin and C-peptide in NODAT and non-NODAT patients treated with tacrolimus were higher than that in healthy volunteers (p50.05). Fasting plasma insulin concentration in NODAT was significantly elevated compared with than that in non-NODAT group (p50.05). But there are no statistical differences in fasting plasma C-peptide concentrations between NODAT and non-NODAT groups. The allele and genotype frequencies of IRS-2 Gly1057Asp and IRS-1 Gly972Arg in NODAT patients were not significantly different from non-NODAT patients (p40.05). In conclusion, insulin resistance is the primary cause of tacrolimus-induced NODAT. The IRS-2 Gly1057Asp and IRS-1 Gly972Arg genotypes are not related to NODAT.
Objectives: Family members’ attitude is the key factor in organ donation. This study aimed to analyze the attitude and willingness of families towards organ donation and to explore the impact of Chinese family culture on voluntary organ donation.Methods: Taking the family as a unit, a total of 15 families (59 family members) were interviewed using the semi-structured interviews.Results: Among the 59 participants, 58 had heard of organ donation, 30 were unwilling to donate organs, 25 had an intention to donate, and 13 were very taboo about it. 29 weren’t giving consent for family members’ donation, only 8 supported families to sign up as donors. Particularly, 7 participants could donate their organs but wouldn’t donate organs of family members. The family culture models were divided into the patriarchal family culture model (4 families), independent family culture model (8 families), patriarchal subversion family culture model (3 families). Based on the influence of social and cultural factors (taking national policy as an example) on the willingness to donate organs of relatives, the family culture models were divided into the stubborn family culture model (3 families), swing family culture model(9 families), and selfless dedication family culture model(3 families). Conclusions: Organ donation is still a taboo topic in Chinese families. Although the patriarchal family cultural model is no longer dominant, the father's thoughts and views still play an essential role in the whole family. Most families belong to the swing family culture model, and the willingness to donate is greatly influenced by social and cultural factors.
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