Correlation of CYP3A5 * 3 gene polymorphisms with sirolimus blood concentration in Chinese stable renal transplant recipients / 中华器官移植杂志

Objective To investigate the effect of CYP3A5 * 3 and MDR1C3435T polymorphisms on the blood trough concentration of sirolimus in the Chinese renal transplantation recipients with stable renal function and the influencing factors for individual differences.Method 112 cases of Chinese renal transplantation recipients with stable renal function were recruited in this study.Related data of the recipients,including gender,age,height and body mass,were recoded.CYP3A5 and MDR1 genotypes were determined by the direct sequencing.Blood trough concentration of sirolimus was measured by using chemiluminescence microparticle immuno assay (CMIA).The influencing factors of individual differences in sirolimus blood trough concentration was analyzed,and the correlation of CYP3A5 * 3 and MDR1C3435T gene polymorphisms with sirolimus blood trough concentration was evaluated.Result Of the 112 cases,there were 10 cases (8.93％) of CYP3A5 * 1/* 1,49 cases (43.75％) of CYP3A5 * 1/* 3,and 53 cases (47.32％) of CYP3A5 * 3/* 3.Allele frequencies of CYP3A5 * 1 and * 3 were 30.81％ and 69.19％,respectively.There were 31 recipients (27.68％) with MDR1 3435CC,60 (53.57％) with MDR1 3435CT,and 21 (18.75％) with MDR1 3435TT.Allele frequencies for C and T at position 3435 of MDR1 were 54.46％ and 45.54％,respectively.In this study,recipients' CYP3A5 * 3 genotype was the main factor (P =0.000) of sirolimus blood trough concentration,but dose,gender,age,height,postoperative time,the level of serum creatinine,hemoglobin levels,combined use of CsA and MDR1C3435T genotype had no effects on sirolimus blood trough concentration (P ＞ 0.05).sirolimus blood trough concentration/(dose weight) in * 1/* 1,* 1/* 3 and * 3/* 3 recipients was (0.0721 ± 0.0202),(0.1055 ± 0.0395),and (0.1395 ± 0.0537) μg·L-1 ·mg-1 ·kg-1,respectively,The sirolimus blood trough concentration/ (dose weight) in * 1/* 3 recipients was 1.46 times higher than that in * 1/* 1 recipients,and that in * 3/* 3 recipients were 1.93 times higher than that in * 1/* 1 recipients.There was significant difference in sirolimus blood trough concentration/(dose weight) between recipients with different CYP3A5 * 3 genotypes (P =0.000).Conclusion The CYP3A5 * 3 gene polymorphism is closely related to the blood trough concentration/dose of sirolimus,and is the main factor of the blood trough concentration of sirolimus between individuals.

A multicenter randomized controlled trial of HC-A Ⅱ solution in kidney preservation / 中华器官移植杂志

ObjectiveTo evaluate the efficacy and safety of HC-A Ⅱsolution in kidney preservation.Methods A multicenter,randomized,double-blind and controlled clinical trial was conducted.Between Jan.2008 and Dec.2010,kidney recipients from 9 transplant centers were randomly divided into two groups.Grafts in each group were perfused and stored in HC-A Ⅱ or HTK solutions respectively.Results277 patients were included in the Full Analysis Set (FAS),137 of whom were inHC-A Ⅱgroup and 140inHTK group. Demographic andbaseline medical characteristics were similar between the two groups.262 patients were included in the Per Protocol Set (PPS),133 of whom were in HC-A Ⅱ group and129 in HTK group.The percentages of patients with a serum creatinine level that returned to normal within 28 days postoperation were 86.9％ in HC-A Ⅱ group and 85.0％ in HTK group respectively (P＞0.05 ).The results from PPS analysis were consistent with those from FAS analysis The incidence of test-related adverse events was 2.9％ in HC-AⅡ group and 0.7％ in HTK group respectively (P＞0.05).No test-related serious adverse events occurred throughout the study.ConclusionHC-A Ⅱ solution,the same as HTK solution,is safe and effective in kidney preservation.

Clinical outcomes in renal allograft recipients switched to long-term immunosuppressive therapy with mycophenolate mofetil after renal transplantation / 中华器官移植杂志

Objective To document the impact of conversion to mycophenolate mofetil (MMF)at different time points after transplantation on the renal function of renal function.Methods A longterm,multicenter,non-interventional and observational study was done.Two cohorts were included:One was Switch cohort (340 cases) including renal allograft recipients who switched to MMF at least 6 months after renal transplantation and followed up for 4 years after switch; The other was Stay cohort (123 cases),including renal allograft recipients who received MMF treatment after transplantation and followed up for 4 years after enrollment.Results GFR values of patients in Switch cohort was significantly increased after switch,and the change in GFR slope was 3.1 mL· min-1 · year-1 (P＜0.01).GFR values of patients in Stay cohort kept steady before and after enrollment,and the change in GFR slope was 0.44 mL·min-1 ·year-1 (P＞0.05).Statistically significant difference in the onset time of GFR decline (defined as 20％ decline from the baseline) was observed among subgroups within Switch cohort (P＜0.01),but there was no significant difference among subgroups within Stay cohort (P＞0.05).Stay cohort was 12％ higher than in Switch cohort every year.Conclusion Conversion to MMF ＞6 months or even many years after transplantation can obviously improve the renal function of recipients.The earlier conversion can benefit improvement of the renal function.

Tacrolimus once daily (Advagraf) vs twice daily (Prograf) in De Novo renal transplantation: a multicentre, randomized, open label, parallel control phase Ⅲ study / 中华器官移植杂志

Objective To compare the efficacy and safety of twice-daily tacrolimus (Tacrolimus BID; Prograf) vs once-daily prolonged release tacrolimus (Tacrolimus QD; Advagraf), combined with steroids and mycophenolate mofetil in preventing acute rejection in De Novo renal transplantation patients. Methods 241 patients from 11 centers were randomized into two groups with 3 months observation period post-transplantation. Advagraf was administered as a single oral dose in the morning (initially 0. 1-0. 15 mg/kg every day) and Prograf was administered in two equal oral doses 12h apart (initially 0. 1-0. 15 mg/kg). Study visits were scheduled for days 1, 3, 7, 14, 28, 56, 84post-transplantion. The efficacy, safety, compliance and adverse effects were compared between two groups. Results Totally 223 patients completed the study. The two groups were comparable in age,gender and primary disease. There were 12 episodes of acute rejection in each group. There was no graft loss or patient death in both groups. The incidence of drug related adverse events was 32. 1 %and 33. 3% respectively in the control and experimental groups. Dosage was decreased in both groups and there was significant difference in each group. The trough level was similar at the initiate period.Twenty-eight days post-transplantation the trough level in the Advagraf group was lower than in the Prograf group. Conclusion Advagraf has the same efficacy, safety and drug related adverse effects as Prograf. It is practical and feasible for Advagraf substitute for Prograf in clinical practice.

A comparison of two methods of extracting impacted mandibular third molars / 实用口腔医学杂志

Objective:To study the feasibility of extraction of impacted mandibular wisdom teeth using turbine drill and new instruments. Methods: 600 patients with impacted mandibular third molars were divides into 2 groups. A group used turbine drill and new instruments to extract the impacted mandibular third molar. B group used the dental chisel to extract the impacted mandibular third molar. The operation time, intraoperative and postoperative complications were recorded to assess the effects of the methods. Results: The operation time of group A and group B was (22.285±12.025 01) min and (16.115±12.078 62) min respectively. The operation time of group A was shorter(P<0.05). The intraoperative and postoperative complication incidence rate was lower(P<0.05). Conclusion: Turbine drill and new instruments method is superior to dental chisel method in the extraction of impacted mandibular wisdom teeth.

Tendency of dyslipidemia in the early stage after renal transplantation: multicenter investigation in Beijing region / 中华器官移植杂志

Objective To investigate the current dyslipidemia profiles and correlation with etiological factors in early stage post-transplantation, and the impact of lipid metabolic disorder on renal function. Methods The clinical data of 1032 renal allografts from eight hospitals in Beijing between 2004 and 2008 were collected and evaluated retrospectively. Before and at the 1st, 3rd, 6th and 12th month post-transplantation, the changes in blood total cholesterol (TC), triglycerides (TG),low density lipoprotein (LDL)-cholesterol and high density lipoprotein (HDL)-cholesterol were analyzed. The difference in the blood lipid disorder at different stages stratified by time and different age group, the effects of immunosuppressive agents on blood lipid, and the impact of blood lipid disorder on the blood creatinine were studied. Results Except HDL-cholesterol, TC, LDL-cholesterol and TG levels were increased gradually at the first year, especially LDL-cholesterol and TG. The TC and LDL-choleaterol abnormalities were obviously related with age (P<0. 01 ). The effect of Tacrolimus (Tac)-based immunosuppressive regimen on the lipid metabolic disorder was less than cyclosporine (CsA). At the first year, there was no significant difference in blood creatinine between lipid-lowering treatment and non-lipid-lowering treatment (P>0. 05). For the recipients not subject to lipid-lowering treatment and their TG level higher than the normal at the first month after operation, the creatinine level at the first year was significantly higher than in those with normal TG level (P< 0. 05). Conclusion The lipid metabolic disorder following renal transplantation is a common complication after the first transplant year, and was related with age and immunosuppressive agent regimen. Tac-based immunosuppressive regimen has little effects on the blood lipid metabolism.

Retrospective clinical analysis on recipients of more than 10 years after renal transplantation / 中华器官移植杂志

Objective To summarize the clinical data of renal transplants survived with graft function more than 10 years and the adverse events during this period, and to discuss the main strategies for the long-term survival Methods Survival rate of renal transplants simultaneously survived with graft function > 10 years and grafts was counted respectively in total 1003 renal transplant recipients at our hospital before Dec. 31,1998 retrospectively. Their relevant survival,adverse events and initial post-operative immunosuppressive regimens were recorded simultaneously.Results As of Dec. 31, 2008, the 10-year survival rate of recipients was 62. 7% (629/1003), and recipients with graft function accounted for 85. 37 % (537/629). Of them, 94. 75 % (596/629) recipients received cyclosporine A (CsA) -based immunosuppression plus other antiproliferative immunosuppressive agents. Post-transplantation adverse events included coronary heart diseases in 57 cases (9. 06 %), liver damage in 32 cases (5. 09 %), malignancy in 29 cases (4. 61% ), diabetic mellitus in 25 cases (3. 97 %), apoplexy in 16 cases (2. 54 %), severe bone marrow depression in 14 cases (2. 23 %), femur head necrosis in 7 cases (1.11%), lower-extremity thrombosis in 3 cases (0. 48 %), sudden deafness in 2 cases (0. 32 %). There were 690 survival patients and 49 deaths including 19 (38. 78 %) due to cardiocerebral vascular accidents, 10 (20. 41%) due to malignancy, 9 (18. 37 %) due to hepatic failure, 4 (8. 16 %) due to infection, 3 (6. 12 %) due to treatment abandonment, 2 (4. 08 %) unknown reasons and 2 (4. 08 %) accidental deaths. Conclusion Long-term survival after renal transplantation is associated with the primary medication of CsA as the main immunosuppressive regimen. The non-immunologic factors such as the prevention and cure of cardioeerebral vascular diseases and the early finding of liver functional abnormality and tumor are the main points focused during follow-up.

Clinical research of domestic tacrolimus in management of rejection following renal transplant / 中华泌尿外科杂志

ObjectiveTo evaluate the efficacy and safety of domestic taerolimus in the manage-ment of acute rejection in renal transplantation reeipienta.MethodsA multieeneter, open and com-parative study for domestic Taerolimua and Prograf was performed. Eighty reeipienta of first allogenie renal transplantation were randomized into 2 groups: ①Experimental group (accepting Fumeixin ad-ministration, n=58) included 23 males and 35 females with the mean age of(39.1±9.6)years. ②Control group(accepting Prograf administration, n=22) included 12 males and 10 females with the mean age of(41.34±8.5)years. There was no significant difference in the volume, warm and cold is-chemia time of donor renal, age and sex of donor. All of the 80 cases accepted tacrolimus (domestic or foreign made, at the dose of 0. 10～0. 15 mg·kg-1·d-1 , q 12 h) treatment that combined with MMF and prednisone posttransplantation. Tacrolimus CO was aimed to 8-12 ng/ml in the first 60 days and 5-10 ng/ml later. The dose of MMF was according to the rule of each transplantation center based on the following recommendation: 1.5-2.0 g/d for the weight above 70 kg, 1.5 g/d for the weight 50-69 kg, and 1.0 g/d for the weight below 49 kg, in two divided doses. Prednisone was ad- ministrated as per ruler of each center. ResultsObservation termination was 3 months. Morbility of actue rejection was 3.40% (2/58)and 13.6% (3/22) in experimental and control group(P>0.05). Ad-verse events including hypertension, hyperlipemia, hyperglycemia and slight abnormality of liver func-tion occurred in 36. 2%(21/58) and 36. 4% (8/22) cases of experimental and control group(P> 0. 05). The survival rate in the 2 groups was 100%. The dose of tacrolimus in experimental group was significantly lower than that in the control group at 8 and 12 weeks posttransplant, while drug valley concentration in serum was proximal in 2 groups during the whole observation period.Conclusion Domestic tacrolimus capsules can be used effectively and safely in the management of acute rejection in renal transplantation.

Two-year experience with rapamycin in kidney transplantation / 中华器官移植杂志

Objective To observe the effects and safety of rapamycin (Rap) in combination with cyclosporine A (CsA) and steroid (Pred) as triple regimen for prevention of acute rejection after renal transplantation.Methods Fifty patients with de novo cadaveric kidney allograft were randomized into two groups. In the study group there were 30 patients treated with Rap, CsA, and Pred, while in the control group there were 20 patients with conventional triple therapy of azathioprine (Aza), CsA, and Pred. Same dosages of CsA and Pred were used in both groups. Any adverse event after treatment was observed and recorded in detail. The laboratory investigations were checked and analyzed periodically.Results The pre-protocol population included 26 patients in study group and 18 patients in control group. The 2-year patient and graft survival rates in both groups were 100 %. The incidence of acute rejection was 3.7 % (1/27) in study group, 25 % (5/20) in control group, respectively. All episodes of acute rejection were reversed by methylprednisolone. The trough levels of CsA kept same in both groups, but CsA dose in study group was lower than that in control group. Blood concentrations of total cholesterol and triglyceride in study group were higher than those in control group. Conclusion Rap is an effective and safe immunosuppressive drug for prevention of acute rejection after renal transplantation. Rap combined with CsA allows reducing the dose of CsA. But its main side effect is hyperlipidemia.

Clinical application of mizoribine in minimizing virus infection risk in renal graft recipients / 中华器官移植杂志

Objective To investigate the clinical application of mizoribine (MZR) in minimizing virus infection risk in renal transplant patients. Methods Four transplantation centers in Beijing participated in this clinical trial, and 112 primary cadaveric renal allograft recipients were enrolled. MZR in combination with CsA and corticosteroids was used for the prevention of acute rejection (AR). The biochemical data were observed and the infections of 7 different viruses were monitored and recorded. Results All patients were followed up for 12-20 months (average 15. 5 months). The patient/graft survival rate was 96% and the morbidity of AR was 11.6%. All ARs were converted. The major side effect was hyperuricimia, which could be controlled without withdrawal of MZR. The morbidity of CMV infection was 11.6% and no CMV diseases occurred. Only one case experienced adenovirus infection. Conclusions MZR is a safe and effective immunosuppressants. Hyperuricimia should be controlled after operation. The morbidity of virus infections was relatively lowered.

Diagnosis and treatment of complete necrosis of the ureter after cadaveric renal transplantation / 中华外科杂志

<p><b>OBJECTIVE</b>To deepen the understanding of patients with complete necrosis of the ureter after renal transplantation for early diagnosis and treatment.</p><p><b>METHODS</b>Of 5 patients with complete necrosis of the ureter after renal transplantatioin between January 1991 and April 2001 in our hospital, 4 were male and 1 was female (mean age, 35 years). Seven to 12 days after renal transplantation, native pyeloureterestomy was performed for 1 patient, and the remaining 4 patients received the cutting of the diatal necrosis ureter and vesicoureterostomy because of urine leakage. Six to seven weeks later when the ureter stents were pull out, native pyeloureterestomy or pyeloureteroplasty was performed for the 4 patients because of uropenia and hydronephrosis.</p><p><b>RESULTS</b>Five patients showed normal function of the kidney postopcreation (follow up: 6 - 12 months) without hydronephrosis.</p><p><b>CONCLUSIONS</b>When distal necrosis of the ureter is observed after renal transplantation, complete necrosis of the ureter may occur. Native pyeloureterostomy or pyeloureteroplasty is an effective treatment.</p>

Analysis of 176 cases of death from kidney transplantation / 中华泌尿外科杂志

Objective To review the cadaveric kidney transplantations at our center in the past 22 years and to analyze the causes and the influencing factors on death in 176 patients who died after renal transplantation. Methods A total of 1 039 patients received cadaveric kidney graftings between October 1977 and June 1999.Patient's mortality was calculated by the Kaplan Meier method.The factors which might lead to patients' death,including age and sex of the donors and recipients,frequency of transplantation,dialysis time and transfusion volume before transplantation,cold ischemic time (CIT),delayed graft fuction (DGF),rejection,immunosuppressive regimen,and post transplant complications,were analyzed by log rank and Cox model. Results Total mortalities of the patient at 1 ,5 ,10 ,and 15 year were 6.9%,19.7%,32.1%,and 34.7%,respectively.The leading causes of patients' death were infection,cardiocerebral vascular diseases,and hepatic failure.The factors of transplant times,dialysis time before transplant,immunosuppressive regimen,chronic rejection,post transplant complications of pneumonitis and cardiocerebral vascular diseases were significant impact on transplant patient death by the analysis of Cox model. Conclusions In this series of 1039 cadaveric kidney transplant patients,the mortality since the first year after transplantation was increased annually by 2.5% during the past 22 years.The leading causes of patients' death are infection,cardiocerebral vascular diseases,and hepatic failure after renal transplantation.Transplant times in which patients receive the procedures,dialysis time before transplant,immunosuppressive regimen,chronic rejection,post transplant complications of pneumonitis and cardiocerebral vascular diseases are significant factors impacting on transplant patients' death.

The effect of L-carnitine on panel reactive antibody / 解放军医学杂志

Objective To explore the effect of L-carnitine on panel reactive antibody (PRA) in hemodialysis patients. Methods 50 patients were classified randomly into 2 groups: L-carnitine group receiving intravenous injection of 2g L-carnitine after each hemodialysis for 6 months, and control group did not receive any L-carnitine treatment. The PRA in serum was measured by enzyme-linked immunosorbent assay (ELISA) before and after 6 months of L-carnitine treatment. Results L-carnitine significantly reduced PRA levels compared with control group(P

Studies on the microchimerism after kidney transplantation / 解放军医学杂志

Objective To investigate the state of microchimerism after kidney transplantation, and to evaluate the relationship between microchimerism and long term survival of transplanted kidney. Methods Leukocytes were collected from peripheral blood of 70 female recipients having received kidneys from males for the identification of microchimerism by means of amplifying the single copied sex determine region Y gene (SRY) by nested PCR. Results Half to 10 years after renal transplantation, the positive percentage of microchimerism in 70 female patients was 58.6%(41/70). These 70 patients were categorized into three groups according to the duration after the transplantation: Group 1(n=25), 0.5 to 2 years; Group 2 (n=27), 2 to 5 years; and group 3 (n=18), over 5 years. The positive rates of microchimerism for three groups were 68%(17/25), 44.4%(11/27) and 72%(13/18), respectively. The positive rates in both group 1 and group 3 were significantly different compared with that in group 2 (P

Clinical study of Simulect in renal allograft recipients / 中华泌尿外科杂志

Objective To evaluate the efficacy and safety of Simulect for the prevention of acute rejection in renal allograft recipients receiving Neoral-based immunosuppressive regimen. Methods A prospective,multicenter and open-label clinical trial was conducted from March to October 2001.A total of 33 patients [20 men and 13 women; age range,18-63 years;mean age,(42.6?11.6) years] who received first kidney allograft were enrolled.Thirty-two cases had panel-reactive antibody

Collagen synthesis in distraction osteogenesis in alveolar cleft / 实用口腔医学杂志

Objective: To observe collagen synthesis in the different phase of distraction osteogenesis(DO) in alveolar cleft.Methods:8 dogs were used to make experimental model of alveolar cleft and underwent the closure of the cleft by distraction osteogenesis.The animals were sacrificed on day 0, 14, 28 and 63 after completion of DO respectively. The samples were examined by histological observation and the expression of typeⅠ,Ⅱ,Ⅲ collagen was studied by immunohistochemistry staining. Results:On day 0, a lot of type Ⅲ collagen fibers were observed in the distraction area. On day 14, there was trabecula bone, collagen Ⅰexpression was stronger than collagen Ⅲ. On day 28, trabecula bone developed into network-like structure with type Ⅰ collagen expression. On day 63,lamellated bone with type Ⅰ collage expression filled the distraction area. No obvious expression of collagen Ⅱ was observed.Conclusions:The formation of new bone is mainly intramembrane osteogenesis along the distraction vector.