Investigation Of Several Important Issues In Clinical Kidney Transplantation

Objective To investigate the safety and efficacy of treatment with Pegylated Interferon and Ribavirin in renal transplant recipients with chronic hepatitis C.Methods Nine adult renal transplant recipients of>12-month duration, infected with HCV, and with stable renal graft function were recruited. All patients were administered with PEG-IFN-α2b50μg/week, plus Ribovirin400-600mg/day. HCV viral load was reexamined monthly. Consolidation therapy lasted for3-9months after initial remission of HCV-RNA. Viral response, adverse effects and changes in hemogram, alanine aminotransferase, and serum creatinine were also monitored.Results The duration of treatment for9patients was4-20months. Sustained virologic response (SVR) occurred in6patients with no relapse during6-month follow up period after the ceasation of the treatment. Two patients, with rapid virologic response, had a virologic relapse after completing their3-month consolidation therapy. One patient maintained no obvious virologic response during8months of treatment. Renal function was kept in normal range in all patients and no one experienced a rejection episode during or after PEG-IFN-α2b therapy. The major adverse reactions included influenza-like syndrome (fever, muscle soreness, anorexia), transient bone marrow suppression and anemia. All of the adverse reactions were transient and tolerable, and no discontinuation of PEG-IFN-α2b therapy was required in all these patients.Conclusions For renal transplant recipients with stable renal graft function, treatment with PEG-IFN-α2b and Ribavirin has high efficacy in the treatment of HCV and is not associated with high risk of acute rejection of renal allografts. Objective To investigate the clinical pattern, therapeutic principle and influencing factors of interstitial pneumonia in renal allograft recipients.Methods The general information, clinical manifestation, treatment and outcomes of30recipients with interstitial pneumonia after renal transplantation from Nov,2006to Dec,2013were analyzed retrospectively.Results29of30patients developed interstitial pneumonia between2to6months post-transplant, showing a more consistent regularity in progression. The total course of the pneumonia lasted for34.9±7.5days on average. The mean duration between the onset to the fastigium of pneumonitis was approximately14.8±1.9days. The mean duration of the fastigium lasted for7.3±3.6days, after that the patients usually started to recover. Long terms of the fastigium usually indicated poor outcomes. The mean duration of the recovery period was13.1±3.7days. After adjusted administration of methylprednisolone, antibiotics, antifungal agents, nutritional support as well as immunosuppressive drugs,23patients with the chest CT scans expressed as mild and moderate were cured and discharged. However,4of the7patients with the chest CT scans expressed as severe were died.Conclusions The progression of interstitial pneumonia after renal transplantation is characterized by a more consistent regularity. After adjusted administration of methylprednisolone, antibiotics, antifungal agents, nutritional support as well as immunosuppressive drugs, renal allograft recipients with interstitial pneumonia could obtain a good therapeutic effect without over-treatment. Objective To compare the in vitro cytotoxic effects of Thymoglobuline and ATG-F on human lymphocytes.Methods Thymoglobulin and ATG-F with the same concentration were sequential diluted to multiple proportions. Peripheral blood lymphocytes from normal human subjects were reacted with Thymoglobulin or ATG-F and then tested by the method of complement-dependent cytotoxicity (CDC) with flow cytometry.Results The in vitro CDC of Thymoglobulin and ATG-F on normal human peripheral blood lymphocytes from6healthy volunteers gradually decreased with increasing dilution titer. Thymoglobulin had a highest CDC (66.24±10.35%) under the dilution of1:1, while the CDC decreased to a level less than10%(5.59±2.59) at the dilution of1:128. Similar to Thymoglobulin, ATG-F displayed the highest CDC at the dilution of1:1, and decreased to a level less than10%(6.31±4.80) at the dilution of1:64. The average CDC level of Thymoglobulin at the dilution of1:16on T and B lymphocytes was51.23%and30.45%, respectively, while ATG-F at the same dilution have similar CDC on T cells (49.84%) and a lower CDC on B cells (24.31%, P<0.05).Conclusion Both Thymoglobulin and ATG-F shows significant cytotoxic effect on normal human peripheral blood lymphocytes. The average cytotoxic effect of Thymoglobulin is approximately2times as that of ATG-F. In addition, Thymoglobulin is more potent than ATG-F to deplete B lymphocytes. Objective To determine the effect of Wuzhi capsule (WZ) on pharmacokinetics of Tacrolimus (Tac) in kidney transplant patients who have taken WZ to reduce the dose of Tac for a long term.Methods Twenty stable renal transplant patients with similar trough level of Tac were divided into a WZ group (n=10) and a control group (n=10) according to the administration of WZ or not. Whole blood concentrations of Tac at0,0.5,1,1.5,2,3,4,6,8and12h post the morning dose were determined. Estimated pharmacokinetic parameters were calculated and compared. Additionally, CYP3A5genotypes of each patient were analyzed using PCR-RFLP to compare the effect of CPY3A5genotypes and WZ on Tac dose requirement.Results Pharmacokinetics data showed that Co of Tac is6.3μg/L in WZ group and5.9μg/L in the control group. The average peak time of Tac is similar (1.4h in WZ group,1.3h in the control group, P>0.05). Both the peak concentration of Tac and AUC0-12h of Tac were slightly higher in WZ group than that in the control group, but the difference didn’t show statistic significance. The frequency of CYP3A5*1/*3genotype is60%in both group, while the average dose of Tac reduced by36%in WZ group than in the control group (0.042mg-kg-l-d-1,0.067mg·kg-1·d-1,P<0.01). In WZ group, the average dose of Tac was even lower in carriers of*1/*1genotype (0.036mg·kg-1·d-1) than that in carriers of*1/*3genotype, which close to the lowest dose requirement in carriers of*3/*3genotype from the control group (0.034mg·kg-1·d-1).Conclusions In kidney transplant patients with CYP3A5*1genotype, a long-term application of WZ to reduce the required tacrolimus dose is a generally safe way without significant changes in regular pharmacokinetics of tacrolimus. For patients with genotye of CYP3A5*1/*1, WZ is particularly suitable.