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Objective To evaluate clinical efficacy and safety of ABO-incompatible (ABOi) living-related kidney transplantation. Methods Clinical data of 23 recipients undergoing ABOi living-related kidney transplantation were retrospectively analyzed. According to the initial blood group antibody titers in the recipients before surgery, different individualized pretreatment regimens were adopted, including oral intake of immunosuppressive drugs plus rituximab, or oral intake of immunosuppressive drugs plus plasma exchange and/or double filtration plasmapheresis plus rituximab. The blood group antibody titers before and after pretreatment, before and after kidney transplantation, and perioperative renal function and related complications were monitored. Renal allograft function and related complications were observed during postoperative follow-up. Results Among 23 recipients undergoing ABOi living-related kidney transplantation, except for one case presenting with hyperacute rejection during operation, the serum creatinine levels of the remaining 22 recipients were restored normal. Perioperative complications included lymphatic fistula in 4 cases, 1 case of urinary fistula, 1 case of perirenal hematoma complicated with T cell-mediated rejection, 6 cases of urinary system infection, 1 case of acute tubular necrosis, 1 case of acute pancreatitis, 1 case of blood group antibody titer rebound, and 1 case of primary disease recurrence, and all of these complications were cured after corresponding treatment. During postoperative follow-up, the graft and recipient survival rates of 22 recipients were 100%, and renal allograft function was normal. The blood group antibody titer were all ≤1:8 during follow-up. Complications during follow-up included 2 cases of severe lung infection, 1 case of antibody-mediated rejection, 2 cases of primary disease recurrence, 1 case of lymphocyst, 1 case of urinary system infection, 1 case of herpes zoster, 1 case of BK viruria and 2 cases of abnormal blood glucose levels. Conclusions ABOi living-related kidney transplantation may be safely performed by selecting individualized pretreatment regimens according to antibody titers by different blood groups. However, high-dose rituximab or combined use of rabbit anti-human thymocyte immunoglobulin may cause severe infectious complications in highly sensitized recipients.
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Introducción: el trasplante renal (TR) es la terapia de elección en la mayoría de los pacientes con insuficiencia renal crónica terminal. El conocimiento cada vez más amplio de la inmunología, la mejoría en las técnicas quirúrgicas, el uso de mejores fármacos inmunosupresores y los cuidados en el seguimiento posterior al trasplante han permitido reducir la incidencia de pérdida de injerto y han mejorado la calidad de vida de los pacientes luego del TR. Objetivo: identificar las complicaciones más frecuentes en las primeras 48 horas en pacientes con TR en un hospital de tercer nivel de atención. Métodos: estudio descriptivo y transversal en una muestra aleatoria de 41 pacientes con TR registrados del 5 de enero al 5 de septiembre de 2017 en un hospital de tercer nivel de atención de la ciudad de Veracruz. La información se recabó del expediente clínico como unidad de análisis. Los datos se analizaron con medidas de tendencia central y dispersión. Resultados: el 65.9% fueron hombres; la edad promedio fue de 35 ± 11.3 años. La principal causa de lesión renal crónica fue etiología no determinada (53.7%) e hipoplasia renal (14.6%). El motivo de egreso fue por mejoría en 97.6%. Solo en 10% de los pacientes se presentaron complicaciones, principalmente trombosis segmentada de vena safena interna (30%), trombosis de injerto (3%), trombosis venosa profunda de segmento femoral (2%) y disminución del flujo vascular renal de polo inferior (2%). Conclusión: las complicaciones que se presentaron en los pacientes postrasplantados de riñón en las primeras 48 horas fueron las de tipo vascular.
Introduction: Kidney transplantation is the therapy of choice in the majority of patients with end-stage chronic renal failure. The increasing knowledge of immunology, the improvement in surgical techniques, the use of better immunosuppressive drugs and post-transplant follow-up care have reduced the incidence of graft loss and improved the patients' quality of life after kidney transplantation. Objective: To identify the most frequent complications in the first 48 hours in patients who underwent kidney transplantation in a third level hospital. Methods: Cross-sectional, descriptive study in a random sample of 41 patients with kidney transplantation registered from January 5 to September 5, 2017, in a third level hospital from the city of Veracruz. The information was collected from the clinical record as an analysis unit. Data were analyzed with measures of central tendency and dispersion. Results: 65.9% of patients were male; the average age was 35 ± 11.3 years. The main cause of chronic renal injury was undetermined etiology (53.7%) and renal hypoplasia (14.6%). The reason for discharge was improved health in 97.6% of patients. Only 10% of patients presented complications, mainly internal saphenous vein thrombosis (30%), graft thrombosis (3%), deep venous thrombosis of the femoral segment (2%) and decreased renal vascular flow of the lower pole (2%). Conclusion: The complications that occurred in patients who underwent kidney transplantation in the first 48 hours were vascular.
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Humans , Quality of Life , Transplantation Immunology , Epidemiology, Descriptive , Cross-Sectional Studies , Kidney Transplantation/adverse effects , Renal Insufficiency, Chronic , Acute Kidney Injury , Graft Rejection , Hospitals, Public , Hospitals, Special , Immunosuppressive Agents , MexicoABSTRACT
Objective To establish a hyperacute rejection model in ABO-incompatible renal allotransplantation in nonhuman primates.Method ABO-incompatible renal transplantation was performed using blood group B cynomolgus monkeys as recipients and blood group A cynomolgus monkeys as donors.The transplants were distributed into 2 groups according to whether the recipient monkey was presensitized or not:(1) non-presensitized control group (n =1),not receiving any pretreatment; (2) KLH-conjugated blood group antigen A (KLH-A) presensitized group (n =3),being presensitized by subcutaneous injection of KLH-A 2 weeks prior to ABO-incompatible renal transplantation.The serum anti-blood group A antibody levels were measured using a FACS method.The graft survival time was observed and the pathologic studies were performed using the endpoint renal graft tissue samples.Result In non-presensitized control group,no hperacute rejection was observed during the surgery.With the traditional CsA triple therapy,the renal allograft survived was more than 30 days without obvious rejection,and the serum creatinine level was 263 μmol/L at day 30.After the presentization with KLH-A,recipient monkeys of KLH-A presensitized group had a markedly increased anti-A antibody levels and rapidly rejected the renal allografts from blood group A donors within 1 h after the reperfusion,which was demonstrated to be a hyperacute rejection with the pathologic studies.Conclusion The strategy of presensitization with KLH-conjugated blood group antigen significantly increases the corresponding blood group antibodies and allows the establishment of a hyperacute rejection model in ABO-incompatible renal allotransplantation in nonhuman primates.
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ObjectiveTo investigate synergistic effect of donor livers blocked by recipient blood serum (RS) and cobra venom factor (CVF) treatment to inhibit hyperacute rejection (HAR) happened in liver xenotransplantation.MethodsThe SD rat blood serum was prepared for pre-perfusing the donor livers before experiment.24 pairs of guinea-pig (GP) and Sprague-Dawley (S.D.) rats were choiced respectively and pair-matched between GP donor and rat recipient randomly.Before transplantation,donor livers of GPs were pre-perfused by 0.5％ SD rat serum.Paired animals were divided into 4 groups randomly such as donor liver perfused by RS,recipient treated by CVF,RS+ CVF performed and Ringer solution as a control.The orthotopic liver xenotransplantations was performed with two-cuff technique.The survival time and liver function of recipients,morphological and pathological changes of rat livers were observed.ResultsThere was no piebaldism change on the recipient liver from experimental group.The survival time of recipients from RS+CVF group [(161.5±30.9) min]was longer than that of control[(45.2 ± 13.9) min] and CVF[(125.2 ± 25.5) min] or RS groups [(88.1±19.7) min] (P＜0.05).The ALT in serum of recipients from RS+CVF [(63.2±13.9)U/L]was lower than that from congtrol group [(126.1±23.3)U/L](P＜0.01) and CVF group [(79.9±18.1)U/L](P＜0.05) or RS group [(106.1±19.3)U/L](P＜0.01) The histological damages including thrombosis,interstitial bleeding and edema of recipient liver from RS+CVF group were alleviated markebly than that of other groups (P＜0.05).ConclusionThere was a synergistic effect to inhibit HAR happened in liver xenotransplantation by blocking the donor liver with recipient blood serum and CVF treatment significantly.
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Objective To investigate the feasibility of inhibiting Galα (1,3)-Gal expression in mouse vascular endothelial cells by lentivirus-mediated RNAi.Methods The shRNA specified to α1,3-GT mRNA was designed and synthesized in vitro and cloned into the lentivirus vector.EOMA cells were infected by recombinant lentivirus.Real-time RT-PCR was used to detect mRNA transcriptional levels of αl,3-GT as well as immunofluorescence and flow cytometry were applied to detect Galα(1,3)-Gal antigen level after gene transfection.Co-culture of infected EOMA and serum of human was done and the survival rate was measured by MTT.Results The αl,3-GT shRNA sequences were cloned into the recombinant lentivirus vector correctly and the lentivirus was produced successfully.The transfection efficiency to EOMA was 75 %.Real-time PCR revealed that the mRNA transcription of α1,3-GT was obviously inhibited by α1,3-GT shRNA recombinant lentivirus with the rate of 88 % (P＜0.05),while there were no obvious differences among control group,no shRNA lentivirus group and negative-shRNA lentivirus group (P＞ 0.05).Immunofluorescence and flow cytometry demonstrated the same results that Galα(1,3)-Gal antigen expression in EOMA transfected by α1,3-GT shRNA lentivirus was less than that of control group,no shRNA lentivirus group and negative-shRNA lentivirus group (P＜0.05),but there were no obvious differences among the later three groups (P＞0.05).After co-culture with serum of human,MTT showed the survival rate of EOMA infected by α1,3-GT shRNA lentivirus was obviously increased (P＜ 0.05).Conclusion Recombinant α2,3-GT shRNA 1entivirus is constructed successfully,which can inhibit the expression of α1,3-GT and Galα1,3-Gal in EOMA by RNAi and control hyperacute rejection in vitro.
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Recombinant expression vector pcDNA3-MCPCD59DP containing human membrane complement regulatory proteins(hCRPs) MCP and CD59 cDNA was constructed successfully by using two independent promoters.After transfected into NIH3T3 cells with calcium phosphate-DNA precipitate method,NIH3T3 pcDNA3-MCPCD59-DP transfectants were obtained by G418 selection.Extraneous genes integration was identified by PCR.The co-expression of human CD59 and MCP at both mRNA and protein levels was confirmed by using RT-PCR and Western blot analysis.Human MCP and CD59 cDNA were integrated in NIH3T3 pcDNA3-MCPCD59-DP genomic DNA after continuous 30 times passages,indicating that NIH3T3 pcDNA3-MCPCD59-DP were stable cell lines.Human complement-mediated cytolysis assays showed that NIH3T3 cells transfected stably with pcDNA3-CD59,pcDNA3-MCP,and pcDNA3-MCPCD59-DP were protected from C-mediated damage and co-expressed human MCP and CD59 provided more excellent protection against C-mediated attack as compared with either CD59 or MCP expressed alone.The dicistronic vector represents an effective and efficacy strategy to overcome C-mediated damage and has potential therapeutic value for effectively controlling complement activation and finally for preventing hyperacute rejection in clinical gene therapy.
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Xenotransplantation is a feasibility way of solving the shortage of human organs for transplantation. Although it is urgently needed to satisfy the demand of people and sustain the function of human organs, there are multiple hurdles existed to clinical application, such as the immune rejection between human body and the xenografts, the infection of pathogens and a series of ethic, morality and social issues. A historical retrospect of xenotransplantation was given, and then probe into the strategies according to the main problems and the actualities. Finally, the prospect in the field of xenotransplantation was showed.
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Objective To investigate the aim antigen coursing the hyperacute rejection of xenotransplantation. Methods Documents about hyperacute rejection in xenotransplantation were reviewed and summarized in detail. Results Pig is thought to be one of the ideal donors of xenotransplantation, but the major obstacle is hyperacute rejection mediated by complement that is activated though human serum. ?-Gal is recognized as the major antigen and its expression is controlled by ?-1,3 galactosyltransferase. Immunoabsorption of pre-exsisted antibody, enzymatic digestion of ?-Gal, knockout ?-GT gene and transgenic technology have been used to solve this problem. Even so, there remain other antigens which can combine with natural antibodies in human serum, such as, 40?10 3 molecule in erythrocyte, 210?10 3, 10 5?10 3 and 50?10 3 antigen in pig embryo brain cell, etc. Conclusion ?-Gal is the major antigen which course the hyperacute rejection. Besides ?-Gal, many nonalpha-gal need further investigation.
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Objective To study Ephedra sinica in preventing hyperacute rejection in guinea pig-to-rat cardiac xenotransplantation. Methods The recipient rats were divided into two groups: control group and experiment group, according to whether administrated complement inhibiting component (CIC) from Ephedra sinica. In 15 min after operation, 4 rats from control group and 4 from experiment group were sacrificed to detect the pathologic changes in cardiac tissues. The complement parameters including CH_(50), APH_(50), and C_(3) were determined during the period of 0, 10, 15, 30, 45 min in serial serum. Results The survival time was significantly prolonged and pathological changes were less in experiment group than that in control group. Conclusion The study reveals that both classical pathway and alternative pathway of complement activation can be induced by xenotransplantation and Ephedra sinica can prolong the xenograft time by inhibiting complement activities and postposing hyperacute rejection.
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Hyperacute or acute accelerated rejection caused by preformed antibody in sensitized patients resulted in increased waiting period and complicated posttransplant hospital course. Intravenous immunoglobulin (IVIG) has known to have anti cytotoxic effect by blocking the anti HLA antibody. PURPOSE: We investigated the effect of IVIG on hyperacute and acclerated rejection of the heart graft in the presensitized rat. METHODS: Recipients (Wistar) were sensitized from repeated allo (Lewis) skin graft and followed by heterotopic allo cardiac transplantation. A guinea pig was used for the xenotransplantation model. IVIG (Green Cross kappa, 400 mg/kg in allotransplantation, 800 mg/kg in xenotransplantation) was given just before heart transplantation. Graft survival and donor specific IgG, IgM and complement were measured. RESULTS: Graft survival was 7.2 days in non sensitized allogenic heart transplantation (n=9), 1.3 days in sensitized allogenic recipients (n=7). Graft survival was prolonged from 1.3 days to 4.4 days with IVIG treatment (n=5). As for xenogenic transplantation, graft survival was prolonged from 30 min to 7.4 hr with IVIG treatment (n=5). Donor specific IgG and IgM and complement increment were blocked by IVIG during the IVIG treatment. Donor specific IgG and Ig M and complement were increased after the cessation of IVIG treatment. CONCLUSION: IVIG was able to prolong the graft survival of the sensitized allograft and xenograft. Suppression of the donor specific IgG, IgM and complement might be one of the underlying mechanisms. A further studies have to follow to clarify the more detailed mechanism.
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Animals , Humans , Rats , Allografts , Complement System Proteins , Graft Survival , Guinea Pigs , Heart Transplantation , Heart , Heterografts , Immunoglobulin G , Immunoglobulin M , Immunoglobulins , Immunoglobulins, Intravenous , Skin , Tissue Donors , Transplantation, Heterologous , TransplantsABSTRACT
Objective:To investigate the effect of 3 HLA matching measures on preventing hyperacute rejection(HAR). Methods:Among 1 152 cases,550 cases received anti donor lymphocytotoxic crossmatch(LXM),335 cases received LXM and HLA serological test,267 cases of the latter again received panel reaction antibody(PRA)test, the change of the HAR rate with different HLA matching measures were analyzed. Results:If LXM value ≤10% or HLA matched loci ≥3,the rate of HAR was unrelated to LXM value or HLA matched loci. HAR rate decreased significantly in patients with LXM and HLA serological test, and decreased more markedly in those with additional PRA test compared with those only with LXM test. Conclusion:HLA test and PRA are necessary and effective to avoid HAR.
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Objective To study the effects of tripterium wilfordii hook f.(T11) used after transplantation on survival of pancreas graft.Methods Male Wistar rats weighing 200-300 g served as donors, while recipients were male SD rats rendered diabetes with strepotozotocin administered intravenously at a dose of 50 mg/kg body weight through tail vein.Vascularized heterotopic whole organ panereaticoduodenal transplantation was performed.The graft exocrine secretion was drained into duodenum by side-to-side anastomoses between the duodenum of donor and recipient.The insulin was drained into systemic vena by anastomoses between inferior vena cava and the infrarenal abnominal aorta of recipient and the donor aorta and portal vein.The vascular anastomoses were done by using microsurgical method.The non-fasting serum glucose and urine glucose reaction were detected at an interval of 2 days and the serum insulin Wasdetected at the 4th day post-transplantation.Results All of the recipients had normoglyeemia and negative urine glucose reaction 24 h after transplantation.The survival time of the pancreatic grafts was as follows: (10.4±2.9)days in group 1,(22.0±1.5)days in group 2.Conclusion Administration of T11 after pancreatic transplantation could prolong the pancreatic graft survival.
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In order to determine the relationship between hyperacute xenograft rejection and oxygen free radical(OFR)formation,in the model of guinea pig to SD rat cardiac xenotransplantation guinea pig heart specimens were obtained at harvesting,after stored in Ringer's lactate solution(4℃)for 1 hour,and at 60 min after transplantation to assess histological changes and OFR production by light microscopy,electromicroscopy and luminol-enhanced chemiluminescence (LC).OFR formation increased significantlly in hyperacute rejection.These findings suggests that OFR may play important role in the pathogenesis of discordant xenograft rejection.