Objective:Preformed anti-human leukocyte antigen(HLA)specific antibodies are a major risk for antibody-mediated rejection.The aim of this study is to detect and analyze anti-HLA specific antibodies in sera of renal transplant candidates for evaluating the status of presensitization.Methods:A total of 3 500 patients awaiting renal transplantation in our hospital from 1998 to 2007 were included in the study.Panel reactive antibody(PRA)in sera of 694 candidates was detected by complement-dependent cytotoxicity(CDC)before March 2000,then the sera of other 2 806 recipients were screened by enzyme-linked immune absorbent assay(ELISA)alternatively.The polymorphism,specificity and relevant factors of anti-HLA antibodies were analyzed.Results:Only IgG type of antibodies specific to HLA classⅠcould be detected by CDC,whereas both anti-HLA classⅠand classⅡ of IgG class could be found out by ELISA.Lower PRA positive rate by CDC(8%)was shown when compared to that by ELISA(17%).Furthermore,multiple types of specific antibodies against HLA-A(20),B(37),CW(8),DR(14)and DQ(7)were determined by ELISA.Some types of the antibodies presented higher frequencies,such as anti-HLA-A2,24,68,23 and 32;B27,56,57 and 7;DR7,4,9,13,17 and 12;CW1,2,6,4 and 8.These high frequenies of anti-HLA antibodies were somewhat different from the distribution of HLA antigens in South China population.There were significantly different positive rates of anti-HLA antibodies between the male and the female,as the male were sensitized mainly through blood infusion and the female were sensitized by either blood infusion or pregnancy.Conclusion:Specific antibodies against HLA can be detected out by ELISA accurately,whereby to find high freguencies of the antibodies and to avoid donor-recipient mismatching at HLA-loci.Detection of preformed anti-HLA and reducion of HLA-mismatched blood infusion to reduce production of anti-HLA antibodies may be the valuable pathway to improve graft survival.

Objective To document retrospectively long-term quality of life (QOF) and safety of living kidney donors.Methods A total of 219 living-related kidney donors which can be followed up had donated their kidneys between May 2004 and Sap.2011.The renal function,complications and QOF were estimaged.Results Donors included 104 men and 115 women with age from 19 to 66 years.Follow-up period was from 12 to 103 months.No cases died.The mean serum creatinine (Scr) was (84.0± 18.7) μmol/L and creatinine clearance (Ccr) was (1.23 ± 0.37) ml/s over 12 months postoperation.The average Ccr was lower in donors age over 50 years than in younger donors.The kidney function was still abnormal in 3 elder donors at end of the study.Thirty donors had hypertension including 5 newly cases.Microscopic hematuria was found in 4 cases.Hyperlipidemia developed in 3 cases.Mild anemia occurred in 2 cases.Femoral head necrosis occured in 1 case.Majority of 18.26％ donors (40 cases) reported weak healthy feeling (mild impact in 31 cases,moderate impact in 7 cases and severe impact in 2 cases).Thirty-five donors reported mild pain of incision (31 cases occasionally,and 4 cases frequently).Conclusion Living kidney donors have good long-term QOF and safety though there still exist risks of renal impact.Close follow-up is required especially in elderly donors.Compliance of donors needs to be further improved.

Mizoribine(MZR), as an orally prescribed immunosuppressive agent, has been applied in the prevention of rejection after kidney transplantation.MZR requires individual dosing due to the variation of bioavailability.However, therapeutic drug monitoring (TDM) of MZR is not well developed in China, as compared to other clinically used immunosuppressive agents.To our knowledge, this is the first TDM review of MZR.Pharmacokinetic characteristic, concentration determination methods and sample selection of MZR were summarized, also the rational therapeutic window was proposed.Furthermore, gene polymorphism and population pharmacokinetics of MZR were estimated.This review will provide reference for TDM-based individual dosing of MZR in renal transplant recipients.

[Objective]This study was designed to investigate capability of the conditioned media that originated from Renca cells to convert CIM~+ CD25~- T cells into CD4~+ CD25~+ T cells,which can exert immunosuppressive effect on effector T cells in vitro and in vivo.[Methods]The common media were mixed with the conditioned media at different ratios,and fresh enriched CD4~+ CD25~- T cells with MACS were cultured in mixed media for 7 days.At end-point of culture,the cells were collected and detected phenotypes in flow cytometer.Moreover,we detected immunosuppressive effect of converted CD4~+ CD25~+ T cells on effeetor T cells proliferation in one-way mixed lymphocytes reaction by using CCK-8,and we observed survival time and histology of grafts.The delayed type hypersensitivity was determined 14 days after transplantation.[Results]The mixed media could increase ratio of CD4~+ CD25~+ Foxp3~+ T cells in conditioned media ratio-dependent(P＜0.05),compared with control groups,when the mixed media contained no mote than 75% of conditioned media.The converted CD4~+ CD25~+ T cells significantly suppress proliferation of effector T cells in vitro,and prolong survival time of grafts,which were(29.6±1.4)d in converted CD4~+ CD25~+ T cells treated groups(P＜0.05),compared with that in untreated groups(9.8±0.6 d)or PBS treated groups(10.9±0.6 d).Moreover,delayed-type hypersensitivity reaction were conducted at day 14 after transplantation in the recipients,and the results showed that less pad swelling in the group treated with converted CD4~+ CD25~+ T cells than other control groups was found,according to measurement of pad swelling.In addition,progressed to complete necrosis of grafts were exhibited in the mice treated with PBS and untreated mice,whereas better healing of grafts and less lymphocytes infiltration were displayed in the mice treated with converted CD4~+ CD25~+ T cells,which were similar to the mice treated with natural regulatory T cells.[Conclusion]The converted CD4~+ CD25~+ T cells with Renca conditioned media play suppressive role in vitro and in vivo.

Objective To analyze the characteristics of tuberculosis (TB) in renal-transplant recipients from our hospital, and summarize the corresponding experiences in diagnosis and management.Methods A retrospective study was performed on 61 documented post-transplant TB cases out of the 2842 patients who received kidney transplantation in the First Affiliated Hospital of Sun Yat-sen University between Jan.1991 and Dec.2010.Results TB in the post-renal-transplant population in our hospital displayed the following characteristics:(1) High incidence (2.1％ ).54.1％ recipients were diagnosed within the first year post-transplant; (2) Lung was the most common site (77.0 ％).There was high prevalence (60.7 ％) of extra-pulmonary TB (lymphatic TB,23.0 ％; pleuritis,13.1 ％; graft,11.5％); (3) Fever (83.6 ％),cough (55.7 ％),sputum (41.0 ％) were the most common clinical manifestations.There were also emaciation (3.3 ％) and enlargement of lymph nodes (18.0 ％); (4) Chest X-ray and CT were of great value during TB diagnosis while purified protein derivative of tuberculin (PPD) skin test had little diagnostic value with a negative result in 56 cases (91.8 ％) ; (5) Liver function damage ( 16.4 ％),kidney function injury (39.3 ％) and peripheral nerve toxicity (3.3 ％) were the main adverse reactions of anti-tuberculosis chemotherapy,also the major cause of anti-TB failure; (6) Pre-transplant TB (17 cases) increased the probability of TB recurrence (4 cases,23.5 ％) post-transplantation; (7) The post-transplant TB patients were accompanied with cellular immune deficiency,resulting in overlapping infection of bacteria,viruses and fungi (19.7 ％); (8) 1- and 3-year patient/graft survival rate of patients with post-transplant TB was 85.2 ％/78.7 ％ and 85.2 ％/75.4 ％ respectively. The accumulative mortality rate reached to 14.8％,while overlapping infection was the major cause of death (66.7 ％).Conclusion Chinese renal transplant recipients still face a high risk of TB because of their immunecompromised state and epidemiological prevalence of the disease. For the high mortality rate and associated serious complications,rapid diagnosis and effective anti-TB chemotherapy are of great value for TB population.

Objective To investigate the pathological type and characteristics of renal allograft in kidney transplantation recipients,and to analyze the relevant clinical conditions and prognosis of renal function.Methods 230 patients received renal allograft biopsy after renal transplantation.The pathological type and characteristics of renal allograft specimens were observed,and the serum creatinine (SCr) in the recipients with different pathological types were analyzed.The function of renal allograft in the recipients was followed-up after one year,and their prognosis was evaluated.Results In 10 cases of protocol biopsy,normal renal tissues were found in 9 cases,IgA nephropathy occurred at the 3rd month after transplantation.In 220 cases having impaired renal function,there were 33 cases of borderline change,45 cases of acute rejection (AR),24 cases of chronic rejection (CR),26 cases of chronic allograft nephrapathy (CAN),and 39 cases of posttransplantation glomerulonephritis (PTGN).Except for above 167 cases,lesions of 28 cases showed multiple pathology types.Furthermore,there were 8 cases of calcineurin inhibitor nephrotoxicity (CNI-NT),7 cases of BK virus nephropathy (BKVN),and 5 cases of acute tubular necrosis (ATN).Five cases could not be diagnosed for little tissue.In the recipients with pathological diagnosis of borderline change,AR,CR,CAN and nephritis,SCr levels were (171 ± 17),(259 ± 25),(343 ± 33),(406 ± 67) and (207 ± 26) respectively.There was significant difference in SCr levels of recipients among the above 5 groups (P＜0.01).One year after biopsy,137 recipients (80.2%) were followed up.The dysfunction rate of renal allograft was 3.1%,18.2%,22.2 %,33.3% and 13.5% respectively.The △SCr was (-47 ± 20.7),(-37.3± 36.9),(25.5 ± 24.3),(13.5 ± 27.7) and (25.2 ± 17.1) μmol/L respectively.Conclusion Complex and diverse pathological changes were showed in renal allograft.Accurate diagnoses come from renal biopsy and clinical analysis may help clinicians select appropriate treatment programs to promote long-term graft survival.

Objective:To explore the application value of modified technique of ureter implantation in murine renal transplantation.Methods:Thirty left donor kidneys from BALB/c mice was transplanted into syngeneic mice. Cuff technique was applied for anastomosing kidney artery and vein. The procedure of ureter-bladder anastomoses shifted from implication-fixation-embedding to fixation-implication-embedding. Operative duration, recipient survival rate and complications were recorded.Results:Time for separating vessels, perfusion and excision of donor graft was (25±3) min, (10±6) s for warm ischemia and (25±5) min for cold ischemia. Time for separating recipient vessels was (12±5) min, (7±1) min for arterial anastomosis, (7±1) min for venous anastomosis, (13±2) min for ureter-bladder anastomosis, (5±1) min for right kidney excision and (5±1) min for abdominal closure. Operative duration was(77±3)min. Twenty-six recipients survived over 3 months. The successful operative rate was 86.7%.Conclusions:With a shorter learning curve, modified technique of ureter implantation is easier and faster so as to reduce the postoperative incidence of urinary tract complications during murine renal transplantation.

The study aims to investigate the associations of SUMO4 polymorphisms with tacrolimus concentrations in Chinese renal transplant recipients. Blood samples and clinical data were collected from 132 renal transplant recipients with tacrolimus treatment. CYP3A5*3 genotypes were detected by PCR-RFLP, and SUMO4 (rs237024, rs237025) genotypes were detected by Sequenom® MassARRAY system. SUMO4 rs237024 and rs237025 genotypes were in complete linkage disequilibrium (D' = 1). The dose-adjusted concentration of tacrolimus in SUMO4 rs237024A-rs237025A (GA-GA +AA-AA) carriers was considerably higher than that in GG-GG carriers (P < 0.05). After stratification by CYP3A5*3 genotypes, SUMO4 rs237024A-rs237025A carriers (GA-GA+AA-AA) had a higher dose-adjusted tacrolimus concentration than that in GG carriers in CYP3A5 expresser (P < 0.05). The results illustrated that SUMO4 rs237024 and rs237025 polymorphisms were associated with tacrolimus concentrations, and the test of these genotypes may be useful for individualized medicine of tacrolimus.

Objective: To observe the effects of 8 week inspiratory muscle training on lung function, respiratory muscle strength, exercise performance, body composition and lipid metabolism in obese college students, and to provide a reference for optimizing rehabilitation plan for obese patients. Methods: A total of 58 obese college students were randomly divided into experimental group(n=28) and control group(n=30). The experimental group received inspiratory muscle training with 50% of maximal inspiratory pressure(P Imax), 3 times a week for a total of 8 weeks. Except for the intensity set to 5% P Imax, other parameters in the control group were the same as those in the experimental group. Lung function, respiratory muscle strength, exercise performance, body composition and blood lipids were measured before and after intervention. Results: The completion rates of the training program (adherence) in the experimental group and the control group were 98.0% and 99.2%, respectively. No serious adverse events occurred during intervention. After intervention, P Imax and 6 minute walk test (6MWT) distance increased (t=-7.44, -4.11, P<0.05), ratings of perceived exertion (RPE) and heart rate decreased after 6MWT (t=2.13, 2.63, P<0.05), but there was no significant difference in lung function, body composition and blood lipid level in the experimental group (P>0.05). There was no significant change in the above indexes in the control group (P>0.05). Conclusion Eight week inspiratory muscle training can effectively improve inspiratory muscle strength and exercise performance in obese college students, whereas it had no effects on expiratory muscle strength, lung function, body composition and blood lipid profiles.

Objective To investigate the characteristics of BK virus (BKV) infection in renal transplant recipients. Methods A total of 243 renal recipients from our clinic within 48 months after transplantation were enrolled as the trial group and 82 healthy people as the control group. Urine and peripheral blood samples of these two groups were harvested for urinary sediment BKV cytology by Decoy cell counting and BKV DNA by real-time PCR. Results The positive rates of urinary Decoy cell, BKV viruria and viremia were 35.4%, 36.6% and 16.9% in trial group, and 4.9%, 20.7% and 2.9% in control group, respectively. In trial group, the medians of urinary Decoy cell, urinary BKV and peripheral blood BKV were 6/10 HPF, 1.00×104 copy/ml and 6.87×103 copy/ml respectively, while in control group, they were 2/10 HPF, 1.10×104 copy/ml and 2.24×1(3 copy/ml. Compared with the healthy people, the positive rates and the levels of BKV DNA in urine and peripheral blood of recipients were significantly higher. The amount of urinary Decoy cells was positively correlated to urinary BKV load (r=0.636, P＜0.01). Conclusions BKV replication is easier to happen in renal recipients as compared to healthy people. Counting of urinary Decoy cells is convenient, useful and sensitive to evaluate BK viruria and viremia in renaltransplant recipients. BKV DNA detection in urine and peripheral blood can be used to screen the evidence of BK reaction in order to prevent irreversible graft damage by BKV.[ Key words ] Kidney transplantation; BK virus; Kidney diseases; Decoy cells