Effect of miR-146a polymorphism on biochemical recurrence risk after radical prostatectomy in southern Chinese population.

Evidence has shown that miR-146a is involved in carcinogenesis and a common G/C variant (rs2910164) in the pre-miR-146a gene has been found to be associated with various cancers. We investigated the potential prognostic role of miR-146a polymorphism in prostate cancer after radical prostatectomy. Seventy-two southern Chinese with prostate cancer undergoing radical prostatectomy were included in this study. miR-146a polymorphism was analyzed by PCR-RFLP. Its prognostic role in biochemical recurrence was assessed using Kaplan-Meier analysis and Cox regression model. We did not find a significant association between miR-146a polymorphism and prostrate-specific antigen failure in the Chinese population [HR (95%CI): 0.83 (0.30-2.32) for CC vs GG/GC]. However, high Gleason score (over 8) was associated with increased biochemical recurrence and poorer PSA-free survival. This study was limited by the length of follow-up. Future studies with longer follow-up would allow evaluation of more direct metrics, such as disease-specific survival, metastasis-free survival, and overall survival.

Meta-analysis confirms that a common G/C variant in the pre-miR-146a gene contributes to cancer susceptibility and that ethnicity, gender and smoking status are risk factors.

Evidence has shown that miR-146a is involved in carcinogenesis, and a common G/C variant (rs2910164) in the pre-miR-146a gene has been associated with various types of cancer. We summarized the data from 22 published case-control studies on the association between rs2910164 and cancer risk and performed subgroup analyses by ethnicity, gender and smoking status. We found a significant association between the pre-miR-146a polymorphism and cancer risk in Caucasian populations (odds ratio (OR) = 0.93, 95% confidence interval (CI) = 0.88-0.99 for G- vs C-allele), while the significance was borderline in Asian populations (OR = 1.11, 95%CI = 1.00-1.23 for G- vs C-allele). A significantly increased risk of cancer was found in males with GG/GC genotypes (OR = 1.23, 95%CI = 1.10- 1.37), and the significance was more pronounced in smokers (OR = 1.82, 95%CI = 1.32-2.51) than in non-smokers (OR = 1.24, 95%CI = 1.01-1.53). We conclude that there is evidence that the pre-miR-146a polymorphism contributes to cancer susceptibilities and that gender and smoking status affect the probability of cancer in individuals with this polymorphism.

Effect of CYP3A5 genotype on renal allograft recipients treated with tacrolimus.

OBJECTIVE: Tacrolimus concentrations are associated with CYP3A5 genotype. The purpose of this study was to evaluate the outcomes and drug concentrations/doses among a posttransplant population with various CYP3A5 genotypes within 12 months. METHODS: Sixty seven kidney recipients receiving immunosuppression with tacrolimus + mycophenolate mofetil + prednisolone were grouped according to their CYP3A5 genotypes (*1/*1; *1/*3; *3/*3). The initial dose of tacrolimus (0.15 mg/kg/d) was adjusted according to achieve a target therapeutic window. All patients underwent a protocol biopsy at 1 month posttransplantation. We assayed serum creatinine and tacrolimus blood trough concentrations to calculate the concentration per dosage during follow-up. We also investigated the incidence of acute rejection episodes and the nephrotoxicity of tacrolimus according to the renal biopsy. RESULTS: There was no significant difference among serum creatinine concentrations. Tracrolimus blood concentrations showed a significant difference at day 7 and 1 month with no significant difference at 3, 6, or 12 months among the three groups. The CYP3A5*3/*3 group showed the largest concentration per dosage (C/D) and CYP3A5*1/*1, the smallest C/D. There was a significant difference among the three groups. The occurrence of an acute rejection episode within 3 months showed a significant difference among the three groups but not from 3 to 12 months after transplantation. Nephrotoxicity was greatest among the CYP3A5*3/*3 group. CONCLUSION: CYP3A5 influenced the blood concentrations of tacrolimus. Our study suggested to choose the initial dosage according to the CYP3A5 genotype to obtain a better outcome and reduce the incidences of acute rejection episodes and nephrotoxicity.

Prognostic effect of lymphocyte subgroup CD4+ and CD8+ cells in peripheral blood in renal transplant patients with cytomegalovirus viremia.

OBJECTIVE: Our aim was to evaluate the prognostic effect of peripheral blood lymphocyte subgroup CD4+ and CD8+ cells on renal transplant patients with cytomegalovirus (CMV) viremia. MATERIALS AND METHODS: Using 41 renal transplant patients with CMV-PCR(+) in peripheral blood and stable values of serum creatinine (SCr), we evaluated the changes in lymphocyte subgroup CD4+ and CD8+ cells with onset of antiviral therapy with gancyclovir for treatment of pneumonia. We compared patients with or without pneumonia. RESULTS: The lower the peripheral blood lymphocyte subgroup CD4+ and CD8+ cell numbers, the higher the incidence of CMV pneumonia. The numbers of CD4+ and CD8+ cells at 1 month posttransplantation and at the time of CMV-PCR(+) detection were significantly lower than those before transplantation in the CMV pneumonia group (P < .01) and also in the nonpneumonia group. CONCLUSIONS: The decrease in peripheral blood lymphocyte subgroup CD4+ and CD8+ cells after renal transplantation in patients with CMV viremia showed prognostic value for pneumonia. Increased CD4+ and CD8+ cells in peripheral blood combined with preemptive therapy may reduce the incidence of pneumonia among patients with CMV viremia.

Therapeutic effect of Tripterygium wilfordii on proteinuria associated with sirolimus in renal transplant recipients.

Sirolimus (SRL) is a potent immunosuppressive drug used to prevent acute allograft rejection after renal transplantation. Nevertheless, the occurrence of proteinuria has recently been recognized among patients on SRL-based therapy. The aim of this study was to investigate the therapeutic effects of Tripterygium wilfordii Hook F. (T II) on proteinuria associated with SRL in renal transplant recipients. According to accepting T II, 36 recipients were divided into 2 groups: T II group (n = 21) and valsartan group (n = 15). The T II group was administered 1 mg/kg/d, and the valsartan group, 80 mg twice per day for 12 months. Efficiency was then evaluated. Complete remission: proteinuria decreased by >50%; partial remission: proteinuria decreased by 20% to 50%; ineffective: proteinuria decreased by <20%. Upon 12-month follow-up, the total effective rates in the T II group and the valsartan group were 95.2% and 86.7% (P < .05), respectively. Twenty of 21 patients with proteinuria in the T II group were negative at 3-month follow-up with disappearance of edema. There were some adverse events that had greater incidence rates in the valsartan group compared with the T II group, such as hyperkalemia (26.7% vs 4.8%). We concluded that the application of T II markedly reduced proteinuria associated with SRL in renal transplant patients.

A single-dose daclizumab induction protocol in renal allograft recipients: a Chinese single center experience.

This study prospectively compared immunoprophylaxis with a single dose of daclizumab versus no induction in kidney transplant recipients treated with a cyclosporine, mycophenolate mofetil, and prednisone-based immunosuppression regimen seeking to observe the impact of a single-dose regimen for prevention of acute rejection among Chinese renal allograft recipients. A total of 118 renal transplant recipients were randomized into a daclizumab induction therapy group (daclizumab group, n = 58) and a no induction group (control group, n = 60). The daclizumab group received a single-dose (1 mg/kg of ideal body weight by intravenous infusion) 2 hours before the operation. There was no induction therapy in the control group. There was no significant difference in the baseline parameters at randomization between the two groups. The mean time to the first episode of acute rejection was 41.2 +/- 3.2 days for the daclizumab group versus 11.2 +/- 4.6 days for the control group. The number of first biopsy-confirmed acute rejection episodes during the 6-months after transplantation was significantly different in the daclizumab (7,12.1%) versus the control group (14,23.3%; P < .001). At the end of 12 months, patient and graft survivals were 100% in the groups with or without daclizumab. We noted that the incidence of infection, including serious infection was similar, in the daclizumab group to that in the control group, 17.2% and 20.0%, respectively. This study showed that a single-dose of daclizumab effectively prevented acute rejection in Chinese renal allograft recipients.

Conversion from cyclosporine to tacrolimus for chronic allograft nephropathy.

We investigate the effect of conversion from a cyclosporine (CsA) based-regimen to a tacrolimus (FK506)-based regimen with respect to graft renal function induced by chronic allograft nephropathy (CAN). Thirty-one patients with a histological diagnosis of CAN were included after other causes of chronic graft dysfunction had been excluded. Conversion to FK506 was undertaken at an initial dose of 0.15 mg/kg/d, which was subsequently adjusted to maintain FK506 whole blood trough levels between 5 and 10 mug/L. The rate of decline of renal function before and after the FK506 conversion was represented by regression lines (slope) of the reciprocal of serum creatinine versus time. To evaluate the effect of conversion on allograft function, we gathered data on serum lipids, blood glucose, proteinuria, and hypertension. When postconversion slopes were compared to preconversion slopes for each patient, 20 patients (64.5%) showed positive regression lines and four patients (12.9%), less negative. Seven patients (22.6%) displayed an increased rate of decline in renal function with regression lines becoming more negative. FK506 was associated with a significant decrease in lipid levels, proteinuria, and hypertension. No patient returned to dialysis at the end of the 36-month follow-up. Conversion from a CsA-based regimen to a tacrolimus-based regimen was an effective alterative for salvage of patients with abnormal graft renal function induced by CAN.

Immunoregulation of thymosin alpha 1 treatment of cytomegalovirus infection accompanied with acute respiratory distress syndrome after renal transplantation.

We are the first to report the use of thymosin alpha1 to treat cytomegalovirus infection accompanied with acute respiratory distress syndrome after renal transplantation. The patients were divided into the thymosin alpha1 group (Zadaxin group, n = 32) and the control group (n = 14). All patients received the same rescue therapy protocol. Suitable antiviral (ganciclovir, 5 mg/kg every 12 hours, intravenously), antibacterial, or antifungal treatment was given if needed. In addition, patients in the Zadaxin group received thymosin alpha1, (1.6 mg) subcutaneously every other day or every day. The rescue success rate was significantly higher in the Zadaxin than in the control group (78.1% vs 50.0%) while the death rate was greatly reduced (21.9% vs 50%). In the Zadaxin group, the CD4(+) lymphocyte level was significantly increased on day 14; so was the ratio of CD4(+) and CD8(+) T-lymphocyte subsets. In the survival group, CD4(+) and CD8(+) lymphocyte cell counts were significantly increased on days 7, 14, and 21 compared with admission. This study suggested that thymosin alpha1 significantly promoted CD4(+) and CD8(+) lymphocytes, repairing cellular immunity and successfully reinforcing resistance to cytomegalovirus disease.

Rescue therapy by immunoadsorption in combination with tacrolimus and mycophenolate mofetil for C4d-positive acute humoral renal allograft rejection.

The aim of this study was to investigate the efficacy of immunoadsorption (IA) in combination with tacrolimus (TAC; 0.14 to 0.16 mg/kg/d) and mycophenolate mofetil (MMF; 1.5 to 2.0 g/d) rescue therapy for C4d-positive acute humoral rejection in nine cadaveric renal allograft recipients. Initial Panel reactive antibody (PRA-I and PRA-II levels were as high as 28.8% +/- 16.2% and 15.3% +/- 8.9%, IA therapy significantly decreased PRA-I and PRA-II levels to 5.9% +/- 2.9% and 2.2% +/- 0.6%, respectively. Total serum immunoglobulin levels were markedly decreased. Repeated allograft renal biopsy in nine patients revealed remission of acute humoral rejection (AHR), and the deposition of C4d disappeared and reduced. With a mean follow-up of 29.4 +/- 5.4 months, patient and allograft survivals were 100%, and renal function remained stable with a mean serum creatinine of 1.1 +/- 0.3 mg/dL. Our findings suggested that a therapeutic approach combining IA and TAC and MMF rescue improved the outcomes of AHR.

Clinical trial of Tripterygium Wilfordii Hook F. in human kidney transplantation in China.

OBJECTIVE: In this study, the effects of Triptergium Wilfordii Hook F.(T II) were assessed on human kidney allograft rejection and long-term survival. METHODS: This study compared treatment with T II(T II group, n=121) to that without T II(control group, n=102) among adult first cadaveric renal transplant recipients. The T II cohort of 121 recipients were divided into a regular dosage group (n=82) and a double dosage group (n=39). No antibody induction was administered to any patient. RESULTS: Biopsy-proven early acute allograft rejection occurred in 4.1% of patients in the T II group versus 24.5% of patients in the control group. No rejection or repeated rejections occurred in the double dosage group at 3 months after transplantation. Acute rejection episodes were milder in the T II than the control group. The incidence of CD25+ cells>10/ mm3 in the allografts at 3 months after transplantation was lower in the T II group than the control group, 15% and 50%, respectively. All patients tolerated T II well over the 5 years of this study. The 5-year graft survival censored for death with function was 96.7% in the T II group and 80.4% in the control group. CONCLUSION: T II was effective to prevent renal allograft rejection and increase long-term renal allograft survival among adult cadaveric renal transplant recipients.