Early intervention of BK virus replication promotes stabilization of renal graft function / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the optimal time window for intervention of BK virus (BKV) replication and its effect on the outcomes of kidney transplant recipients (KTRs).</p><p><b>METHODS</b>A retrospective analysis of the clinical data and treatment regimens was conducted among KTRs whose urine BKV load was ≥1.0×10copies/mL following the operation between April, 2000 and April, 2015. KTRs with urine BKV load <1.0×10copies/mL matched for transplantation time served as the control group.</p><p><b>RESULTS</b>A total of 54 recipients positive for urine BKV were included in the analysis. According to urine BKV load, the recipients were divided into 3 groups: group A with urine BKV load of 1.0×10-1.0×10copies/mL (n=22), group B with urine BKV load >1.0×10copies/mL (n=24), and group C with plasma BKV load ≥1.0×10copies/mL (n=8); 47 recipients were included in the control group. During the follow-up for 3.2-34.5 months, the urine and plasma BKV load was obviously lowered after intervention in all the 54 BKV-positive recipients (P<0.05). Eighteen (81.82%) of the recipients in group A and 19 (79.17%) in group B showed stable or improved estimated glomerular filtration rate (eGFR) after the intervention; in group C, 4 recipients (50%) showed stable eGFR after the intervention. In the last follow-up, the recipients in groups A and B showed similar eGFR with the control group (P>0.05), but in group C, eGFR was significantly lower than that of the control group (P=0.001). The recipients in group A and the control group had the best allograft outcome with stable or improved eGFR.</p><p><b>CONCLUSION</b>Early intervention of BKV replication (urine BKV load ≥1.0×10copies/mL) in KTRs with appropriate immunosuppression reduction can be helpful for stabilizing the allograft function and improving the long-term outcomes.</p>

Anti-MICA antibodies: risk factors for sensitization and the impact on renal transplantation outcomes / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the risk factors for sensitization of anti-MICA antibodies and their impact on the outcomes of renal transplantation.</p><p><b>METHODS</b>Luminex flow cytometry were used to identify 10 MICA antibodies and evaluate the antibody specificity in 98 uremic patients positive or negative for anti-MICA antibodies undergoing kidney transplantation. The factors contributing to MICA sensitization were analyzed, and the incidence of acute rejection and graft function recovery time were compared between the positive and negative cases for anti-MICA antibodies.</p><p><b>RESULTS</b>Of the 98 uremic patients, 16 (16.3%) were positive for anti-MICA antibodies. The positive and negative cases showed significant differences in the history of blood transfusion, pregnancy, transplantation, and PRA status (P<0.05). In the 38 renal transplant recipients, 6 experienced acute graft rejection, which was reversed by methylprednisolone pulse therapy; of the 10 recipients positive for anti-MICA antibodies, 4 showed acute graft rejection as compared to 2 out of the 28 recipients negative for anti-MICA antibodies (P=0.031). The cases positive for anti-MICA antibodies showed a significantly longer graft function recovery time than the negative cases (14.6∓4.7 vs 8.2∓4.5 days, P=0.001).</p><p><b>CONCLUSIONS</b>Blood transfusion, pregnancy, and transplantation all contribute to the production of anti-MICA antibodies. Patients positive for anti-MICA antibodies may require strict HLA matching and more potent immunosuppressive drugs to prevent renal graft rejection and improve graft survival.</p>

Trichostatin A inhibits the activation of CD(4)(+) T cells by suppressing CD(28) expression in mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the mechanism of trichostatin A(TSA), a histone deacetylase (HDAC) inhibitor, in inhibiting the activation of CD(4)(+) T cells in mice.</p><p><b>METHODS</b>The CD(4)(+) T cells isolated from the spleen of C57BL mice were treated with different concentrations of TSA (2, 20, and 200 nmol/L) for 24 h, and CD(3), CD(28) and interleukin-2 (IL-2) mRNA levels were measured with reverse transcription-polymerase chain reaction. The protein expressions of CD(3), CD(28) and IL-2 were measured by fluorescence-activated cell sorting and ELISA analysis. ZAP70 and PI3K protein expression in CD(4)(+) T cells activated by CD(3) and CD(28) monoclonal antibody were analyzed by Western blotting.</p><p><b>RESULTS</b>TSA dose-dependently inhibited the transcription and protein expression of CD28 in CD(4)(+) T cells and reduced the expression of PI3K protein in activated CD(4)(+) T cells, without showing significant effect on the expression of ZAP70. TSA treatment of the cells also resulted in significantly decreased mRNA and protein expressions of IL-2 (P<0.01).</p><p><b>CONCLUSION</b>TSA can regulate the immunological activity of CD(4)(+) T cells by inducing mRNA and protein expressions of CD(28), which inhibits the activation of the co-stimulatory signal transduction in CD(4)(+) T cells and decreases the secretion of IL-2.</p>

Pulmonary infection in kidney transplant and liver transplant recipients / 南方医科大学学报

<p><b>OBJECTIVE</b>To summarize the features of pulmonary infection (PI) in kidney transplant (Ktx) and liver transplant (Ltx) recipients for effective control measures.</p><p><b>METHODS</b>A retrospective analysis was conducted among Ktx recipients and Ltx recipients with PI during the period from Jan 2004 to Dec 2008. The clinical data concerning the infection was compared.</p><p><b>RESULTS</b>Forty-five Ktx recipients and 23 Ltx recipients developed PI after the transplantation. The incidence of PI was 7.4% and 56.1% in (P<0.001), respectively, with severe PI occurring in 2.6% and 46.3% of the recipients (P<0.001). The median time from PI diagnosis to transplant was 230 days (29-1080 days) and 4 days (2-104 days) (P<0.001), the case-fatality rate for PI was 6.7% and 17.4% (P=NS), and the mortality rate was 0.5% and 9.8% (P<0.001) in Ktx and Ltx recipients, respectively; Gram-negative organisms were the most common in both Ktx and Ltx recipients, but Ltx recipients had significantly higher incidence of multidrug-resistant bacteria (12.9% vs 37.0%, P=0.005).</p><p><b>CONCLUSION</b>The knowledge of PI after the transplantation will benefit appropriate prophylactic and empirical treatment to improve the survival of Ktx and Ltx recipients.</p>

Long-term survival of high-risk kidney transplant patients / 中华外科杂志

<p><b>OBJECTIVE</b>To summarize the experiences in high-risk renal transplant recipients for ketter long-term survival.</p><p><b>METHODS</b>From April 1991 to December 2008, a total of 921 kidney recipients with high-risk factors were divided into six groups as following: (1) pediatric patients (< 18 years old) (GI, n = 34); (2) retransplant recipients (GII, n = 169); (3) high sensitized patients (PRA> 30% or peak PRA > 50%)(GIII, n = 35); (4) elderly recipients (> 60 years old) (GIV, n = 297); (5) diabetic patients (GV, n = 112); (6) patients with HBV/HCV infection or HBV/HCV carrier (GVI, n = 274). Each group was compared to a control of 807 recipients without any above risk factor for patient and graft survival at 1, 3 and 5 years. Incidences of acute rejection (AR), chronic rejection (CR) and complication were analyzed and compared respectively between the studied subjects and the control group as well.</p><p><b>RESULTS</b>Compared with the control group, patient/graft survivals were lower in GII, GIII and GVI (all P < 0.05), GIV had worse patient survival (P < 0.05); AR and CR incidences were greater in GI and GIII (all P < 0.05); GIV, GV and GVI had more complications.</p><p><b>CONCLUSIONS</b>This study suggests the benefits for long-term outcome in high-immunological risk renal transplant recipients of low acute selection incidence rate, and reduction of complication incidences is the key to long term results for non-immunological high risk recipients.</p>

Analysis of natural killer cell immunoglobulin-like receptor genes in Chinese / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the genotypes of natural killer cell immunoglobulin-like receptor (KIR) genes and their frequencies in Chinese subjects and explore the mechanism of the actions of nature killer cells.</p><p><b>METHODS</b>The DNA samples were obtained from 67 randomly selected unrelated Chinese Han individuals for genotyping of the KIR genes using PCR with sequence-specific primers (PCR-SSP), and the frequencies of the KIR genes in these Chinese subjects were compared with the reported frequencies in populations of other nationalities.</p><p><b>RESULTS</b>Sixteen KIR genes were identified in these Chinese subjects, and 87.5% of these genes were expressed at frequencies above 0.35. Fourteen functional KIR genes combined into 25 KIR genotypes, among which the most frequent genotype KIR-2DL1-2DL3-2DL4-3DL1-3DL2-3DL3-2DS4 showed a frequency of 0.373, while the frequencies of all the other genotypes were no greater than 0.09. Comparison of the KIR combinations in Chinese Han population with those of Japanese, Korean, and Caucasians populations identified 8.93% of the KIR combinations shared by all these populations; the Chinese, Koreans and Caucasians shared 5.36% common KIR combinations, whereas only 1.79% common combinations were found in Chinese and Caucasians. In this study, 16 new gene combinations were identified (25.28%).</p><p><b>CONCLUSION</b>This study shows the high-frequency distribution of a single KIR gene polymorphism. The KIR combination KIR-2DL1-2DL3-2DL4-3DL1-3DL2-3DL3-2DS4 has the highest frequency in Chinese, Japanese, Korean and Caucasian populations, indicating that inhibitory signal transduction pathway plays an important role in the function of the natural killer cells. This study provide clues for new approaches for improving the prognosis of kidney transplantation by enhancing or inhibiting the function of the natural killer cells instead of life-time usage of immunosuppressive agents.</p>

Expression of Notch1 on peripheral lymphocytes before and after acute graft rejection following renal transplantation / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the changes in Notch1 expression on peripheral lymphocytes after acute graft rejection after renal transplantation.</p><p><b>METHODS</b>Twenty renal transplant recipients experiencing acute graft rejection and 20 without acute rejection were enrolled in this study. Flow cytometry was used to detect the expression of Notch1 on peripheral lymphocytes of the patients before operation, at the occurrence of acute rejection and after anti-rejection therapy. The rates of Notch1-positive lymphocytes measured at different time points were compared between the two groups.</p><p><b>RESULT</b>In patients with acute graft rejection, Notch1 expression at the time of rejection onset was significantly higher than that before operation (t=4.245, P=0.000) and that of patients with graft rejection (t=3.839, P=0.000), and was obviously decreased after anti-rejection therapy (t=3.102, P=0.004). Patients without graft rejection showed no significant changes in Notch1 expression after the transplantation (P=0.409). Notch1 expression was comparable between the recipients receiving Tac therapy and those with CsA therapy (P>0.05).</p><p><b>CONCLUSION</b>Monitoring Notch1 expression on the peripheral lymphocytes after renal transplantation may help in the diagnosis of acute graft rejection and prediction of the effect of an anti-rejection therapy.</p>

Simultaneous liver-kidney transplantation in polycystic kidney and hepatic disease with kidney and liver failure / 中华外科杂志

<p><b>OBJECTIVE</b>To review the clinical experiences concerning simultaneous liver-kidney transplantation in polycystic kidney and hepatic disease with kidney and liver failure.</p><p><b>METHODS</b>This study involved 8 cases of simultaneous liver-kidney transplantation in polycystic kidney and hepatic disease with kidney and liver failure. There were 5 male and 3 female patients, aged from 41 to 67 years old with a mean of 52.8 years old. Six cases transplanted kidney after liver with orthotopic liver transplantation, and 2 cases transplanted liver after kidney with piggy-back liver transplantation. The acute rejections, complications, liver function, kidney functions, and survival rates of patient/liver/kidney were recorded.</p><p><b>RESULTS</b>Within the follow-up of 28 to 65 months, all 8 patients are still alive with normal liver and kidney functions: 2 living more than 5 years, 2 living more than 4 years and 4 living more than 2 years. 2 cases of pleural effusion and 1 case of pneumonia were complications after operation, which had been cured successfully. No acute rejection of allograft was observed.</p><p><b>CONCLUSIONS</b>Simultaneous liver-kidney transplantation is a safe and effective treatment for polycystic kidney and hepatic disease with kidney and liver failure.</p>

Combined assay of soluble CD30 and hepatocyte growth factor for diagnosis of acute renal allograft rejection / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the value of detection of both preoperative soluble CD30 (sCD30) and hepatocyte growth factor (HGF) level 5 days after transplantation in the diagnosis of acute rejection of renal allograft.</p><p><b>METHODS</b>Preoperative serum sCD30 levels and HGF level 5 days after transplantation were determined in 65 renal-transplant recipients using enzyme-linked immunosorbent assay. The recipients were divided according to the sCD30 levels positivity. Receiver operating characteristic (ROC) curves were used to assess the value of HGF level on day 5 posttransplantation for diagnosis of acute renal allograft rejection, and the value of combined assay of the sCD30 and HGF levels was also estimated.</p><p><b>RESULTS</b>After transplantation, 26 recipients developed graft rejection and 39 had uneventful recovery without rejection. With the cut-off value of sCD30 of 120 U/ml, the positivity rate of sCD30 was significantly higher in recipients with graft rejection than in those without (61.5% vs 17.9%, P<0.05). Recipients with acute rejection showed also significantly higher HGF levels on day 5 posttransplantation than those without rejection (P<0.05). ROC curve analysis indicated that HGF levels on day 5 posttransplantation was a good marker for diagnosis of acute renal allograft rejection, and at the cut-off value of 90 ug/L, the diagnostic sensitivity was 84.6% and specificity 76.9%. Evaluation of both the sCD30 and HGF levels significantly enhanced the diagnostic accuracy of acute graft rejection.</p><p><b>CONCLUSION</b>Combined assay of serum sCD30 and HGF levels offers a useful means for diagnosis of acute renal allograft rejection.</p>

Association between transforming growth factor beta-1 gene polymorphism and chronic allograft nephropathy / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the association between transforming growth factor beta-1 (TGF-beta1) gene polymorphism and chronic allograft nephropathy (CAN).</p><p><b>METHODS</b>Fifty patients with failed renal allografts and clinically and histopathologically confirmed CAN were enrolled in this study along with another 50 renal transplant recipients with normal graft function. The DNA extracted from whole blood of the patients was amplified with PCR with sequence-specific primers for determining TGF-beta1 genotypes (position +869, codon 10 and position +915, codon 25). According to documented descriptions, the patients were classified into high and moderate-to-low cytokine production genotypes. The distribution frequencies of high production genotypes was then compared between CAN and non-CAN groups. To eliminate interference in the analysis of the association between TGF-beta1 polymorphism and CAN, other possible risk factors for CAN were screened, including the patients' gender, age, HLA match, delayed graft function, acute rejection, immunosuppressive regimen, cytomegalovirus infection, hypertension, and high cholesterol.</p><p><b>RESULTS</b>CAN patients showed significantly greater proportion of high cytokine production genotype than the non-CAN group [70% (35/50) vs 38% (19/50), Chi(2)=10.306, P=0.001). Of the screened risk factors for CAN, only acute rejection showed some difference between the two groups, but analysis after subgrouping according to acute rejection did not suggest its influence on CAN, which supports the result that the rate of high production genotype was significantly higher in CAN group than in the non-CAN group.</p><p><b>CONCLUSION</b>Most CAN patients have high TGF-beta1 production genotype, which might be a risk factor for CAN after renal transplantation. TGF-beta1 genotyping can be of value in predicting the risk of CAN after renal transplantation.</p>

Application of tacrolimus and cyclosporine A in HBV-carrying renal transplant recipients / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare the long-term effect and safety of tacrolimus (FK506) and cyclosporine (CsA) in kidney transplant (KT) recipients carrying hepatitis B Virus(HBV).</p><p><b>METHODS</b>A total of 109 patients with HBV were randomized into FK506 group (52 cases) and CsA group (57 cases) after KT, and a 2-year-long follow-up of the patients was conducted to record the patient and graft survival, incidence of acute graft rejection and postoperative liver function.</p><p><b>RESULTS</b>The 2-year patient/graft survival was 86.0%/73.7% and 94.2%/90.3% in CsA and FK506 groups, respectively (P<0.05), with incidence of acute rejection of 10.5% and 9.6% (P>0.05), and rate of abnormal liver function of 26.3% and 15.4% (P<0.05), respectively. Eight patients (14.4%) in CsA group required a drug conversion but none in FK506 group. The drug conversion resulted in significant reduction of ALT/AST level from 255.13+/-31.38/201.88+/-21.25 U/L to 31.25+/-11.50/25.13+/-9.68 U/L (P<0.01).</p><p><b>CONCLUSION</b>For HBV-carrying renal transplant recipients, FK506 as the primary choice of immunosuppressant can be more effective and safer than CsA.</p>

Preparation and functional identification of testicular Sertoli cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To simplify the method for separation and cultivation of rat testicular Sertoli cells with high viability, quantity and expression efficiency.</p><p><b>METHODS</b>Testicular Sertoli cells from 2 to 3-week-old male Wistar rats were prepared by digestion with collagenase, trypsin and DNase and cultured together with active lymphocytes to observe their killing effect against lymphocytes. After cell culture for 72 h, the Sertoli cells were morphologically observed by different means and identified with transmission electron microscope. Fas ligand and follicle-stimulating hormone receptor (FSHR) were examined immunohistochemically to identify testicular Sertoli cells. SABC method was used for labeling the Fas ligand on the testicular Sertoli cells.</p><p><b>RESULTS</b>The viability of the isolated and cultured Sertoli cells was more than 90%, and in in vitro culture, Sertoli cells, which expressed the Fas ligand, could kill the active lymphocytes.</p><p><b>CONCLUSION</b>This method improves the efficiency in acquisition of rat testicular Sertoli cells expressing Fas ligand, which are believed to be a potential donor for co-transplantation with parathyroid cells to offer immune privilege.</p>

Clinical observation on long-term surviving patients after combined abdominal organ transplantation / 中华外科杂志

<p><b>OBJECTIVE</b>To summarize the treatment experience of long-term surviving patients after combined abdominal organ transplantation.</p><p><b>METHODS</b>From October 2001 to January 2005, 19 patients received combined abdominal organ transplantation in Nanfang Hospital, including 6 with simultaneous kidney-pancreas transplantation (SKPT), 12 with combined liver-kidney transplantation (CLKT), and 1 with simultaneous liver-pancreas transplantation (SLPT). The periods of follow up were from 6 months to 3 years and 8 months. Summarize primary diseases of the patients, factors which impacted on patients long-term survival rate, and immunological characteristics of combined abdominal organ transplantation.</p><p><b>RESULTS</b>All of 19 transplant cases were performed successfully. Among then, 18 were followed up; 16 survived till now; 2 patients undergoing liver-kidney transplantation were dead, one of which died from myocardial infarction in the 18 months after operation, and one died from cytomegalovirus in infection of lung in 13 months; 1 liver-kidney transplantation patient and 2 pancreas-liver transplantation patients experienced acute rejection once; 2 patients were found nephrotoxicity. Among the 18 patients, 4 patients' survival time were over 3 years, 7 over 2 years, 6 over 1 year, 1 over 10 months.</p><p><b>CONCLUSIONS</b>Combined abdominal organ transplantation is effective for treatment of two abdominal organ failure diseases. Factors which impact on patients long-term surviving include choosing suitable recipient, high quality of donated organ, avoidance of surgical complication, the history of myocardial infarction before operation, immunosuppressive regime and virus infection late after transplantation. Combined abdominal organ transplantation has some different immunological characteristics from single organ transplantation.</p>

Simultaneous liver-pancreas-duodenum transplantation: one case report and review of the literature / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of treatment on end-stage liver disease and type-I diabetes mellitus with simultaneous liver-pancreas-duodenum transplantation.</p><p><b>METHOD</b>In September 2003, one patient with chronic hepatitis B, liver cirrhosis, hepatic cellular cancer, and insulin-dependent diabetes received simultaneous orthotopic liver and heterotopic pancreas-duodenum transplantation. Liver and pancreas graft function was monitored after transplantation.</p><p><b>RESULTS</b>The function of pancreas allograft was recovered immediately and the patient became insulin-independence postoperatively. The liver allograft was experienced an acute rejection episode and reversed by intravenous bolus methylprednisolone. The recipient was currently liver disease-free and insulin-free more than 21 months.</p><p><b>CONCLUSIONS</b>The simultaneous liver-pancreas-duodenum transplantation is an effective method in the treatment of end-stage liver disease and type-I diabetes mellitus.</p>

Clinical observation on long-term survival in patients after simultaneous kidney-pancreas transplantation(report of 6 cases) / 中华泌尿外科杂志

Objective To summarize the experience of long-term survival in patients after simulta- neous kidney-pancreas transplantation(SKPT)with modified enteric drainage(ED).Methods From October 2001 to July 2004,6 patients with end-stage renal disease due to Type 1 diabetes underwent SKPT with modified ED,ie,side-to-side anastomosis between the duodenum of donors and jejunum of recipients. The medication regimen included:mycophenolic acid 500 mg and tacrolimus 2 mg before operation;methyl- prednisolone(MP)1.0 during operation;and 2-dose anti-IL-2 receptor monoclonal antibody(2 cases)or antihuman thymocyte globulin(ATG)(4 cases)for immune induction therapy;MP was used on the first 3 d after transplantation,triple immunosuppressive therapy(tacrotimus,mycophenolic acid and prednisone)was used on the second d after transplantation.Anticoagulants such as low molecular heparin or alprostadil were used for 7-10 d to prevent thrombosis in pancreas graft.Somatostatin was used as prophylaxis for graft pan- creatitis.Ganciclovir was used to prevent cytomegalovirus infection when renal graft gradually recovered 3 to 5 d after transplantation.The follow-up was from 1 year and 3 months to 4 years and 1 month.Results Transplantation was successful in all 6 cases.The blood sugar levels were 6-16 mmol/L.Low-dose insulin was used for 5-10 d,then the blood sugar levels returned to normal range.One of 6 patients experienced nephrotoxicity because of high tacrolimus blood concentration at 7 d after operation;after 3 dialyses and re- duction of tacrolimus dose,the renal allograft regained normal function.Three cases experienced alimentary tract hemorrhage at 14,20 and 22 d,respectively,after operation;the bleeding was stopped after treatment. There were no complications such as pancreatic fistula,intestinal fistula and thrombosis early after operation. All the patients are now alive,specifically,1 survived over 4 years,3 over 3 years,1 over 2 years,and 1 over 1 year.All had normal blood sugar free of insulin use.Five cases had normal renal graft function,with normal sCr,and 1 had sCr＞400?mol/L. Two cases were admitted to hospital due to upper respiratory infection and furuncles in the skin of head 6 months and 2 years,respectively,after operation.They were both cured.No complications such as urinary infection,metabolic acidosis and dehydration occurred.Conclusions SKPT is effective for the treatment of end-stage renal disease due to Type 1 diabetes.SKPT with modified ED are relatively simple with physiological compatibility and fewer complications.High quality of donated organs, HLA matching,pancreatic drainage pattern,rational periopcrative medications and infection late after trans- plantation are important factors affecting the long-term survival of the patients.