Effect of pregnane X receptor polymorphisms on tacrolimus blood concentrations and the resulting adverse reactions in kidney transplantation recipients.

We investigated the effect of pregnane X receptor (PXR) polymorphisms on tacrolimus (FK506) blood trough concentrations and the associated adverse reactions in kidney transplantation recipients (KTRs). Polymerase chain reaction (PCR)-restriction fragment length polymorphism was used to detect the genotypes of single nucleotide polymorphism loci in 336 KTRs. The PXR six-base deletion mutation was classified using specific allele PCR, and the FK506 blood trough concentration in the KTRs was measured by chemiluminescent microparticle immunoassay. There were significant differences in adverse reactions resulting from FK506 in age, weight, body mass index (BMI) and treatment course (P < 0.05). Logistical regression revealed that the FK506 treatment course and BMI were risk factors for hyperlipidemia, and the risk of hyperlipidemia increased 27.534 times when the BMI was less than 18.5. Moreover, age was also a risk factor leading to hyperglycemia. FK506 blood trough concentration and C0/D value had an impact on adverse reactions induced by hyperglycemia. The KTRs' PXR rs3842689, rs6785049, and rs1523127 mutation frequencies were 26.07, 11.79, and 16.07%, respectively. There was no statistically significant difference in the mutation frequency of each locus between the control group and the adverse reaction groups. Therefore, rs3842689, 7635G>A (rs6785049), and 24381C>A (rs1523127) PXR polymorphisms have no obvious impact on FK506; furthermore, the PXR rs3842689 wild-type homozygous WW genotype is a risk factor of FK506 and results in gastrointestinal reactions.

Effects of Wuzhi capsule on blood concentration of tacrolimus after renal transplantation.

This study aimed to investigate the effects of Wuzhi capsule on blood concentration of tacrolimus after renal transplantation. Sixty patients after allogenic renal transplantation were enrolled in this study and randomly divided into an experimental group and a control group. One oral Wuzhi capsule was taken in the morning and evening for patients in the experimental group, while none was given to the control group, maintaining the trough blood concentration of tacrolimus in the normal range. After 3 weeks, the changes of tacrolimus dosage and hepatorenal function in the two groups were compared. Comparisons of drug dosage and blood concentration C0 value of tacrolimus before initiating the experiment showed that there was no statistically ignificant difference (P>0.05) between the two groups. The differences of blood concentration of tacrolimus and hepatorenal function for patients in both two groups after 3 weeks’ treatment also showed no statistical significance (P>0.05), whereas a statistically significant decrease was demonstrated in the tacrolimus dosage of the Wuzhi capsule group compared with that of the control group (P=0.0083). After renal transplantation, Wuzhi capsules were added so as to enable tacrolimus to reach a suitable blood concentration, which can prevent the occurrence of renal transplantation rejection, thus alleviating the economic burden of patients and producing larger social benefits.

Association between SNPs in vascular endothelial growth factor polymorphisms and risk of renal cell carcinoma: a case-control study.

We conducted this case-control study to assess the role of the VEGF -2578C/A, +1612G/A, +936C/T and -634G/C gene polymorphisms in the development of renal cell carcinoma (RCC). A hospital-based case-control study was conducted in a 360 consecutive primary RCC patients and 360 age and gender-matched controls during January 2010 and January 2014. The polymerase chain reaction-restriction fragment length polymorphism was used for VEGF -2578C/A, +1612G/A, +936C/T and -634G/C genotyping. Multivariate conditional logistic regression analyses showed that subjects carrying the AA and the CA+AA genotypes of VEGF -2578C/A had significant association with increased risk of RCC compared to those having the CC genotype, and the ORs (95%CI) were 1.77 (1.10-2.85) and 1.37 (1.01-1.86), respectively. Using the conditional logistic regression model, CA+AA genotype of VEGF -2578C/A had a significantly increased risk of RCC in ever cigarette smokers, and individuals with hypertension, and the ORs (95%CI) were 1.93 (1.08-3.45) and 2.57 (1.06-6.57), respectively. In conclusion, our results showed that AA genotype of VEGF -2578C/A genetic variants is associated with increased risk of RCC.

Study on the effects of regulatory T cells on renal function of IgAN rat model.

OBJECTIVE: CD4+CD25+ regulatory T cells (Tregs) plays a key role in maintaining immune tolerance. IgAN has a close relationship with the immune response. However the significance of CD4+CD25+ T cells to improve renal function of IgAN patients is not clear. The purpose of this study is to evaluate renal function of experimental IgAN rats treated by CD4+CD25+ Tregs cells. MATERIALS AND METHODS: CD4+CD25+ Tregs were separated from the blood of SD rats by immunomagnetic beads, and amplified in vitro. The amplified in vitro and cultured 2*106 CD4+CD25+ Tregs were infused intravenously into IgAN rat model, 3 times every other day. The serum creatinine, urea nitrogen, urinary protein and red blood cells were detected in the fourth and eighth week. The glomerular damage was evaluated by pathological analysis. RESULTS: Tregs cells can be amplified largely in vitro. After CD4+CD25+ T cells were infused into IgAN rat model, urine protein and red blood cells were improved. The glomerular injury can be improved by pathological analysis. CONCLUSIONS: CD4+CD25+ regulatory T cells can significantly improve the symptoms of immunoglobulin A nephropathy (IgAN) rat model, and have clinical application prospect.