ABSTRACT
With the maturity and development of surgical techniques, as well as the improvement of perioperative management level, the success rate of kidney transplantation has been significantly improved. However, due to evident differences in heredity and antigenicity between donors and recipients, rejection will occur after kidney transplantation, which will affect the survival of renal grafts. Immunosuppression is an important treatment for rejection, which is of significance to reduce the risk of rejection and enhance graft survival rate. Nevertheless, immunosuppressants may cause multiple complications while lowering the incidence of rejection, such as infection, cardiovascular diseases and tumors, etc., which seriously affect the quality of life of patients and may even lead to their death. Reasonable selection of immunosuppressants and continuous optimization of immunosuppressive regimen for recipients play a critical role in improving the survival of recipients and renal grafts. In this article, the development history of organ transplantation, immune induction therapy and immune maintenance therapy was reviewed, and the progress in the optimization of immunosuppressive regimens for kidney transplant recipients was discussed, aiming to provide reference for improving clinical prognosis of kidney transplant recipients.
ABSTRACT
Liver retransplantation is the final option for graft failure after liver transplantation. The interval between the first and second liver transplantation will directly affect surgical indications, technical difficulties and treatment outcomes of adult liver retransplantation. Previous studies have shown that the overall survival of liver allografts and recipients after liver retransplantation is significantly lower than that after the first liver transplantation. However, with comprehensive progress in organ preservation methods, anesthesia management concepts, intensive care strategies, surgical techniques and new immunosuppressive drugs, clinical efficacy of adult liver retransplantation has been significantly improved. In this article, the changes of indications, timing of operation, long-term efficacy and its influencing factors, technical difficulties, selection of immunosuppressive regimens and the implementation of living donor liver retransplantation were reviewed, and the achievements, challenges and potential solutions of adult liver retransplantation were summarized, aiming to provide reference for enhancing clinical efficacy of adult liver retransplantation.
ABSTRACT
The application of combination antiretroviral therapy (cART) has significantly prolonged the life expectancy of patients infected with human immunodeficiency virus (HIV). However, viral infection and adverse reactions of cART drugs make patients more prone to organ failure. Solid organ transplantation has become a standard treatment for HIV-infected patients with end-stage organ failure. Nevertheless, among HIV-positive soild organ transplant recipients, multiple problems remain to be resolved, such as increased incidence of graft rejection, increased infection risk, drug toxicity and drug interaction between cART therapy and immunosuppressive drugs, etc. It is extremely challenging to deliver appropriate management for HIV-positive soild organ transplant recipients. Therefore, the application of immune induction therapy, calcineurin inhibitors, mammalian target of rapamycin (mTOR) inhibitors and other immunosuppressive drugs in HIV-positive soild organ transplant recipients was reviewed, aiming to provide reference for subsequent management of immunosuppression in HIV-positive soild organ transplant recipients.
ABSTRACT
Objective:We employ different regimens of induction therapy in living donor ABO-incompatible kidney transplantation(ABOi-KT) recipients to compare their clinical outcomes during 6 months post-KT.Methods:A retrospective analysis was conducted for the relevant clinical data of 41 ABOi-KT recipients from June 2018 to September 2022.Thirteen recipients on induction therapy of anti-human T lymphocyte porcine immunoglobin(pATG)were enrolled in pATG group; 19 recipients on induction therapy of basiliximab in basiliximab group; 9 recipients on induction therapy of rabbit anti-human thymocyte immunoglobulin(rATG)in rATG group.Differences in age, gender, body mass index(BMI), dialysis modality/duration, sideness of donor kidney, frequency of blood group antibody treatment, dose of rituximab, basic blood group antibody titers of IgG/IgM, and the gender and BMI of recipient's donor were compared for three groups.Immune status was assessed by comparing absolute lymphocyte count before pre-treatment and within 6 months post-KT in recipients under different induction regimens among 3 groups by one-way analysis of variance.Transplant kidney function was assessed by comparing the levels of serum creatinine, estimated glomerular filtration rate(eGFR)and serum urea nitrogen using one-way analysis of variance.The incidence of delayed graft function(DGF), acute rejection(AR)and infection was compared among three groups.Results:Regarding baseline profiles, except for donor age pATG group[(60.23±6.10)years]versus basiliximab group[(51.95±6.97)years]was statistically significant( P=0.002), the differences in the remaining parameters were not statistically significant among three groups(all P>0.05). At Day 1/3/7/10/14 post-KT, absolute lymphocyte counts were(0.17±0.07)×10 9/L, (0.27±0.14)×10 9/L, (0.85±0.40)×10 9/L, (1.05±0.56)×10 9/L and(1.10±0.56)×10 9/L in pATG group and(0.69±0.04)×10 9/L, (0.18±0.21)×10 9/L, (0.57±0.44)×10 9/L, (0.67±0.45)×10 9/L and(0.81±0.46)×10 9/L in rATG group respectively.They were all higher than those in basiliximab group[(0.46±0.18)×10 9/L, (0.67±0.26)×10 9/L, (1.29±0.48)×10 9/L, (1.56±0.49)×10 9/L, (1.75±0.53)×10 9/L]and the differences were statistically significant(all P<0.05). No statistically significant difference existed in absolute lymphocyte count among 3 groups before pre-treatment and after Day 21 post-KT(all P>0.05). At Week 1/2/4/12/24 post-KT, the differences in serum levels of creatinine and urea nitrogen were not statistically significant( P>0.05). At Month 1/3 post-KT, eGFR was(47.24±14.51)and(49.94±14.31)ml·min -1·(1.73 2) -1 in rATG group and they were lower than(67.36±21.60)and(65.00±14.67)ml·min -1·(1.73 2) -1 in basiliximab group with a statistically significant difference( P<0.05). However, at Week 1/2/24 post-KT, no statistically significant difference existed in eGFR among 3 groups( P>0.05). In ATG, basiliximab and rATG groups, DGF(1 case, 1 case, 1 case), AR(2 cases, 2 cases, 1 case)and infection(4 cases, 7 cases, 3 cases)occurred during 6 months post-KT. Conclusions:Through a limited sample of single centers, no statistically significant difference existed in graft function recovery for ABOi-KT recipients on induction therapies of pATG, basiliximab and rATG.And DGF, AR and infections occurred in all three groups.However, there were little inter-group differences.
ABSTRACT
Because of the current national organ allocation policy of "pediatric donor kidneys are given priority to pediatric recipients", Chinese pediatric kidney transplantation has achieved rapid development, but the outcomes of pediatric kidney transplantation need to be further systematically summarized.In this paper, by summarizing the characteristics of children's immune system and related research progress, the incidence and influencing factors of acute rejection after pediatric kidney transplantation, the prevention effects of rabbit anti-human thymocyte immunoglobulin (rATG) and anti-CD25 monoclonal antibody induction therapy on acute rejection after pediatric kidney transplantation were compared, and suggestions were put forward for their future application.
ABSTRACT
Objective:To summarize the incidence of acute rejection (AR) after pediatric kidney transplantation (KT) at a single center and examine its impact on graft/patient survival and risk factors for AR.Methods:This is a retrospective cohort study including pediatric recipients who underwent kidney transplantation in past 8 years.After excluding recipients of graft thrombosis within a week post-transplant and lost to follow-ups, a total of 143 cases were ultimately recruited and assigned into two groups of AR (n=29) and non-AR (n=114).Basic profiles of both donors and recipients and graft/patient survival rate were compared between two groups.Relative risk factors for AR episodes were also examined by Logistic regression.Results:Renal grafts for 130/143 cases (90.9%) were harvested from deceased donors and 120(83.9%) cases from children.Twenty-seven transplants (18.9%) were performed in infants and young recipients aged < 3 years.During a median follow-up of 33 months, 34 AR episodes occurred in 29(20.3%) patients.Rate of re-transplantation (27.6% vs. 7.9%), pediatric donor (96.5% vs. 80.7%) and rabbit anti-human thymocyte globulin (rATG) induction (79.3% vs. 36%) were significantly higher in AR group than non-AR group ( P=0.007, P=0.046, P<0.001).Multivariate regression analysis indicated that basiliximab induction caused a significant reduction in the risk of AR incidence as compared with rATG induction (odds ratio 0.13, 95% confidence interval 0.04-0.43, P<0.001).The median time of AR incidence was 1.3 months post-transplantation and 23 episodes (67.6%) were confirmed by biopsy.After anti-rejection treatment, 52.9%(n=18) of the cases achieved a full recovery and 38.3% (n=13) had improved graft function.However, 3 cases (8.8%) developed irreversible graft failure.The 1/3-year graft survival rates were significantly lower in AR group than those in non-AR group (75.3% vs. 95.2%, 68.4% vs. 90.4%, P=0.01), and there was no significant difference in 1-and 3-year patient survival rates between two groups. Conclusions:The incidence of AR is relatively high in pediatric renal transplantation, which has an impact on graft survival.Basiliximab induction can effectively reduce the risk of AR.
ABSTRACT
Objective:To explore the efficacy and safety of low-dose rabbit anti-human thymocyte globulin (rATG) for induction therapy of kidney transplantation (KT) in children.Methods:From October 2018 to May 2021, clinical data were reviewed retrospectively for 77 pediatric KT recipients on a low-dose rATG induction protocol.Recipient/graft survival rate, renal function recovery, acute rejection (AR) and adverse reactions were observed at 1 year post-operation.The postoperative changes of renal function were examined by Friedman’s test; According to the preoperative baseline data, Pearson’s Chi-square or Fisher's exact test was utilized for examining the influencing factors of postoperative AR.Results:A total of 16(20.78%) recipients had AR within the first 6 months post-operation.The incidence of delayed graft function (DGF) was 14.29%(11/77); The incidence of severe infection post-transplantation 18.18%(14/77), the infection rate of BK virus 25.97%(20/77) and the incidence of neutropenia 32.47%(25/77).The recipient/graft survival rate at 1 year post-operation was 97.40%(75/77) and 94.81%(73/77) respectively.Chi-square test indicated that the incidence of postoperative infection in children with body weight ≤30 kg and height ≤138 cm was 28.95%(11/38) and 27.50%(11/40) respectively, Both were higher than 7.69%(3/39) and 8.11%(3/37) of children with body weight >30 kg and height>138 cm.The difference between groups was statistically significant ( P=0.016 and 0.028). Conclusions:Low-dose rATG is generally excellent in preventing AR in pediatric KT recipients.And the risk of related AR may be lower.The infection rate of recipients with decent preoperative development is low.
ABSTRACT
Chronic fatigue syndrome （CFS） is a heterogeneous disease with dysfunction in multiple systems and multiple organs. Its etiology and pathogenesis have not been fully clarified， and its treatment also lacks specificity. The key to studying CFS is developing animal models that reflect the underlying mechanisms and etiology of CFS. The existing CFS modeling methods are complicated and not unified. By sorting out relevant literature，the present study evaluated the modeling methods，modeling standards，mechanisms， and clinical coincidence of the immune model，the stress model， and the disease-syndrome combination model in traditional Chinese medicine （TCM）. The immune model is mainly constructed from the perspective of pathophysiology， with easy operation and wide investigation， which can simulate the pathological characteristics of CFS to ensure pathogenesis research，but the experimental repeatability is general. Stress modeling is a common method for a variety of neuropsychiatric diseases，including CFS. Many different stressors can be employed to investigate the etiology of CFS， but their effects are unpredictable. Compared with the two western medicine models mentioned above，the TCM disease-syndrome combination model integrates modern medicine with TCM theory，with high clinical coincidence and great practical value. However，the TCM disease-syndrome combination model of CFS is still in the exploratory stage with a few types of models，which needs to be further improved， aiming to establish scientific，reasonable，simple， and efficient animal models to provide support for exploring the etiology，pathogenesis， and new treatment ideas of CFS.
ABSTRACT
Objective To evaluate the efficacy and safety of basiliximab (BAS) and antithymocyte globulin (ATG) in immune induction therapy in kidney transplantation by systematic review and Meta-analysis. Methods Prospective randomized controlled clinical trials screening and comparing BAS and ATG in immune induction therapy in kidney transplantation were systematically searched from global databases, screened and compared. The quality of clinical trials was evaluated by Jadad scoring system and data extraction was performed. The effects of BAS and ATG on the incidence of acute rejection, survival rate of kidney allografts, survival rate of recipients, incidence of delayed graft function, infection, cytomegalovirus infection, malignant tumor, leukopenia and thrombocytopenia at 1 year after kidney transplantation were analyzed. Results A total of 10 clinical trials in English consisting of 1 721 kidney transplant recipients were searched, including 883 cases in the ATG group and 838 cases in the BAS group. No significant differences were observed in the incidence of acute rejection, survival rate of kidney allografts, survival rate of recipients, incidence of delayed graft function, infection, cytomegalovirus infection and thrombocytopenia at postoperative 1 year between the ATG and BAS groups (all P > 0.05). The incidence of malignant tumor and leukopenia at postoperative 1 year in the ATG group were significantly higher than those in the BAS group (both P < 0.05). Conclusions The use of ATG and BAS for immune induction therapy in kidney transplantation yield equivalent efficacy at postoperative 1 year, but BAS is safer than ATG. Clinical trials related to stratified analyses of immune risk are urgently required to achieve individualized precision treatment.
ABSTRACT
In recent years, clinical efficacy of pediatric kidney transplantation has been gradually enhanced with persistent progress of organ allocation policy, surgical technologies and perioperative management, etc. However, immunosuppressive management still plays a significant role in the long-term prognosis of pediatric kidney transplant recipients. Due to the disparity from adults in physiology, psychology, immune system and drug metabolism, immunosuppressive management in children should be delivered in a specific manner. Therefore, it is necessary to select appropriate immunosuppresants and formulate individualized immunosuppressive regimens according to the characteristics of pediatric kidney transplant recipients in clinical practice. In this article, the characteristics of immunosuppressive therapy, selection of immunosuppresants, glucocorticoid withdrawal, immune monitoring and medication compliance management of pediatric kidney transplant recipients were investigated, aiming to provide reference for optimizing immunosuppressive management and improving clinical prognosis of pediatric kidney transplant recipients.
ABSTRACT
With the development of immunosuppressants and optimization of immunosuppressive regimens, the survival rates of kidney transplant recipients and grafts have been significantly increased, whereas the incidence of acute rejection and delayed graft function have also been significantly reduced. However, the standard triple immunosuppressive regimen (calcineurin inhibitor+antimetabolite+glucocorticoid) still cannot effectively control the rejection of transplant kidney. Consequently, immune induction before transplantation has been proposed. Immune induction therapy may delay the application time and reduce the dosage of calcineurin inhibitor, lower the incidence of short-term acute rejection after operation, and improve the middle- and long-term prognosis of the recipients. In this article, research progresses on monoclonal antibody-based immune induction regimen, polyclonal antibody-based immune induction regimen and mesenchymal stem cell-based immune induction regime were investigated, aiming to provide reference for optimizing the immune induction regime for kidney transplantation.
ABSTRACT
The risk of early acute rejection after kidney transplantation is relatively high, which severely affects the quality of life of the recipients. In 2009, Kidney Disease: Improving Global Outcomes (KDIGO) recommended that immune inducers should be included in the immune-inducing regime before kidney transplantation, aiming to provide certain strength of immunosuppression during this critical phase and effectively reduce the incidence of acute rejection following kidney transplantation. At present, the selection, efficacy and safety of immune inducers remain controversial among transplantation centers around the world. In this article, clinical efficacy of monoclonal antibodies including interleukin-2 receptor antagonist, alemtuzumab, rituximab and polyclonal antibody antithymocyte globulin in immune induction therapy before kidney transplantation were compared and literature review was performed at home and abroad, aiming to provide reference for promoting the individualized selection of immune inducers for kidney transplantation and improving the quality of life of recipients.
ABSTRACT
Objective To compare clinical efficacy and safety between standard double-and single-dose of basiliximab in renal transplantation.Methods A total of 121 patients undergoing allogeneic cadaveric renal transplantation in Department of Urology of Renmin Hopsital of Wuhan University from January 2008 to May 2011 were recruited as study subjects.Among them,53 patients were assigned into the double-dose of basiliximab group and they were intravenously administered with 20 mg of basiliximab before and 4 d after surgery according to product description.Sixty-eight cases were allocated in the single-dose of basiliximab group and they were given with 20 mg of basiliximab before renal transplantation.The changes of immune function in two groups during perioperative period were monitored.The incidence of adverse reactions including delayed graft function (DGF),acute rejection,pulmonary infection and the survival of patients and renal grafts were statistically compared between two groups.Results There was no significant difference in preoperative humoral immune and cellular immune function between two groups.Compared with preoperative period,cellular and humoral immune function in both groups were inhibited by varying degree at 5 d after surgery (both in P <0.05).Compared with patients in the single-dose group,cellular and humoral immune functions were evidently suppressed in the double-dose group (both in P <0.05).Compared with the parameters assessed at 5 d after surgery,cellular and humoral immune functions were restored to varying degree at 15 d after surgery,whereas still significantly lower than preoperative levels (CD3,CD4,IgM and IgA).Partial parameters (CD8 and IgG)were persistently inhibited and continued to decline compared with the levels at 5 d after surgery.The incidence of DGF was 8% in the double-dose group,and 7% in the single-dose group.During 1-year follow-up,the rejection rates in the double-and single-dose groups were 13% and 12%,and the incidence of pulmonary infection was 9% and 10%.No statistical significance was noted between two groups in terms of these parameters (all in P >0.05).The 1-year survival of patients in the double-and single-dose groups was 94% and 98%,93% and 96% for the survival of renal grafts.No statistical significance was found between two groups (both in P >0.05).Conclusions Both double-and single-dose of basiliximab are efficacious in renal transplantation and do not increase the incidence of adverse reaction.The 1-year survival rates of patients and renal grafts between two groups are almost equivalent.Detection of immune function during perioperative period effectively guides individualized immune induction therapy.
ABSTRACT
Objective To study the preoperative treatment and prognosis observation? in sensitized recipients of kidney transplantation.Method Forty-one recipients positive for preoperative PRA accepted renal allograft transplantation from January 2007 to July 2012.All recipients were given immunosuppressant or immune induction by anti-CD25rnAb in advance,and plasma exchange,immunoadsorption and intravenous high-dose immune globulin were administered.Meanwhile,donor HLA antigens had to avoid all stored HLA antibodies of the recipient,and lymphocyte cytotoxicity cross test (CDC) had to be negative.Anti-human lymphocyte globulin (ATG) was used to strengthen the immune induction,and tacrolimus + mycophenolate mofetil (MMF) + corticosteroids triple immunosuppressive regimen was adopted after transplantation.Then intravenous micafungin would be given after transplanted kidney function was normal,and ganciclovir and sulfamethoxazole were taken orally to prevent infection.Result In 41 recipients positive for preoperative PRA,13 cases were positive for only HLA class Ⅰ antibodies,15 cases for only HLA class Ⅱ antibodies,and there existed 13 cases of both HLA class Ⅰ and class Ⅱ antibodies also with PRA≥50％.Fifteen patients achieved normal serum creatinine in one week,and no hyperacute rejection and accelerated rejection occurred.Fourteen recipients experienced an episode of acute rejection (34.15％,14/41): 12 recovered by steroids bolus therapy,and the other two reversed in 3-5 days by cyclophosphamide or ATG treatment.One case died of mycotic pneumonia in 4 months later.One-year recipient/kidney survival rate was 97.6％ (40/41).Conclusion The recipients positive for preoperative PRA only can accept renal allograft transplant while the donor's HLA antigens had to avoid all stored HLA antibodies of recipients themselves and CDC test was negative.After that the combination of desensitization therapy,immune induction therapy and postoperative potent immunosuppressant can prevent acute rejection effectively and increase postoperative recipient/kidney survival rate.
ABSTRACT
BACKGROUND:Daclizumab can be special y combined with the inerleukin-2 receptor on the surface of activated T cells in human body, and this method can reflect the close of interleukin-2 receptor thus inferring the effect of induction therapy. At present, the daclizumab has been widely used in renal transplantation, but there is no consensus on its clinical application in liver transplantation. OBJECTIVE:To investigate the expression of serum CD25+T cells and soluble interleukin-2 receptor in the patients receiving daclizumab for liver transplantation during perioperative period. METHODS:A total of 58 patients received orthotopic liver transplant for the first time were included and then the patients were randomly divided into two groups:control group (n=28) and treatment group (n=30). The patients in the two groups were treated with tacrolimus, mycophenolate mofetil and corticosteroids triple immunosuppressive regimen. The patients in the treatment group received immune induction therapy with daclizumab, and the patients in the control group did not receive daclizumab. RESULTS AND CONCLUSION:Flow cytometry and enzyme-linked immunosorbent assay showed the expression levels of CD25+T cells in the treatment group were significantly lower than those in the control group at different time points after liver transplantation (P<0.01);and the expression levels of soluble interleukin-2 receptor in the treatment group were lower than those in the control group during transplantation and at the first day after transplantation (P<0.05, P<0.01). At 6 months after transplantation, the incidence of acute rejection was decreased in the treatment group (P<0.01). The results indicate that daclizumab can effectively suppress the expression level of CD25+T cells, as wel as the expression level of soluble interleukin-2 receptor in the peripheral blood in the early stage of liver transplantation, thus effectively reducing the rate of acute rejection.
ABSTRACT
Objective To evaluate the clinical efficiency of humanized anti-CD52 monoclonal antibody (Campath-1H) and anti-CD25 monoclonal antibody (Zenapax) induction therapy in intestinal transplantation patients.Method The data of 6 patients receiving Campath-1H and 5 patients receving Zenapax induction therapy in intestinal transplantation between 2007 and 2012 were analyzed retrospectively.The counts of peripheral blood lymphocytes and monocytes,incidence of rejection and infention,and liver and kidney toxicity of recipients were recorded before and 3 months after transplantation.Results Of 6 intestinal transplantation patients receiving Campath-1H induction therapy,1 died of acute heart failure on the postoperative day 3,and the rest 5 patients had a powerful depletion of lymphocytes and monocytes in 8 weeks,followed by gradual increases after 8 weeks.The percentage of peripheral blood CD3 + T cells,CD4 + T cells,and CD8 + T cells was dropped to 5％ before administration,and remained at a steady low level in the first 8 weeks after induction.Of 5 patients receiving Zenapax induction therapy,1 died of Aspergillus infection on the postoperative day 25,and the rest 4 patients had an obeivous increase of lymphocytes and monocytes on the postoperative day 1.Counts of lymphocytes and monocytes kept steady at normal levels from the 1st to 12th week.One case of mild rejection was found in Campath-1H group.One case of mild,one moderate and one severe rejection were detected in Zenapax group.All rejections were successfully cured by prompt anti-rejection therapy.There were no significant difference in serum creatimine,urea nitrogen,alanine aminotransferase or total bilirubin after 3 months in comparison to preoperation.Conclusion Both Campath-1H induction therapy and Zenapax induction therapy successfully induce immune tolerance in patients with intestinal transplantation.Campath-1H seems to offer better immunosuppression against Zenapax during the first 3 months posttransplantation.