Objective:Compared with long-term renal replacement therapy,kidney transplantation is the ideal treatment for end-stage renal disease(ESRD),significantly extending patient life and improving quality of life.Kidney tra...Objective:Compared with long-term renal replacement therapy,kidney transplantation is the ideal treatment for end-stage renal disease(ESRD),significantly extending patient life and improving quality of life.Kidney transplant patients need to adhere to lifelong immunosuppressive medication regimens,but their medication adherence is generally poor compared with other organ transplant recipients.Medication adherence is closely related to medication literacy and psychological status,yet related studies are limited.This study aims to investigate the current status of medication adherence,inner strength,and medication literacy in kidney transplant patients,analyze the relationships among these 3 factors,and explore the mediating role of inner strength in the relationship between medication literacy and medication adherence.Methods:A cross-sectional survey was conducted from March to October 2023 involving 421 patients aged≥18 years who visited kidney transplantation outpatient clinics at 4 tertiary hospitals in Hunan Province.The inner strength,medication literacy,and medication adherence of kidney transplant patients were investigated using the Inner Strength Scale(ISS),the Chinese version of the Medication Literacy Assessment in Spanish and English(MedLitRxSE),and the Chinese version of the Morisky Medication Adherence Scale-8(C-MMAS-8),respectively.Univariate analysis was performed to examine the effects of demographic and clinical data on medication adherence.Correlation analysis was conducted to explore the relationships among medication literacy,medication adherence,and inner strength.Significant variables from univariate and correlation analyses were further analyzed using multiple linear regression,and the mediating effect of inner strength was explored.Results:Among the 421 questionnaires collected,408 were valid,with an effective rate of 96.91%.The scores of C-MMAS-8,MedLitRxSE,and ISS were 6.64±1.16,100.63±14.67,and 8.47±4.03,respectively.Among the 408 patients,only 86(21.08%)patients had a high level of medication adherence,whereas 230(56.37%)patients had a medium level of medication adherence,and 92(22.55%)patients had poor medication adherence.Univariate analysis indicated that the kidney transplant patients’age,marital status,education levels,years since their kidney transplant operation,number of hospitalizations after the kidney transplant,and adverse drug reactions showed significant differences in medication adherence(all P<0.05).Correlation analysis showed that inner strength positively correlated with both medication literacy(r=0.183,P<0.001)and medication adherence(r=0.201,P<0.001).Additionally,there was a positive correlation between medication adherence and medication literacy(r=0.236,P<0.001).Inner strength accounted for 13.22%of the total effect in the mediating role between medication literacy and medication adherence.Conclusion:The level of medication adherence among kidney transplant patients needs improvement,and targeted intervention measures are essential.Inner strength mediates the relationship between medication literacy and medication adherence in these patients.Healthcare professionals should focus on enhancing medication literacy and supporting patients’inner strength to improve medication adherence.展开更多
BACKGROUND Early hospital readmissions(EHRs)after kidney transplantation range in incidence from 18%-47%and are important and substantial healthcare quality indicators.EHR can adversely impact clinical outcomes such a...BACKGROUND Early hospital readmissions(EHRs)after kidney transplantation range in incidence from 18%-47%and are important and substantial healthcare quality indicators.EHR can adversely impact clinical outcomes such as graft function and patient mortality as well as healthcare costs.EHRs have been extensively studied in American healthcare systems,but these associations have not been explored within a Canadian setting.Due to significant differences in the delivery of healthcare and patient outcomes,results from American studies cannot be readily applicable to Canadian populations.A better understanding of EHR can facilitate improved discharge planning and long-term outpatient management post kidney transplant.AIM To explore the burden of EHR on kidney transplant recipients(KTRs)and the Canadian healthcare system in a large transplant centre.METHODS This single centre cohort study included 1564 KTRs recruited from January 1,2009 to December 31,2017,with a 1-year follow-up.We defined EHR as hospitalizations within 30 d or 90 d of transplant discharge,excluding elective procedures.Multivariable Cox and linear regression models were used to examine EHR,late hospital readmissions(defined as hospitalizations within 31-365 d for 30-d EHR and within 91-365 d for 90-d EHR),and outcomes including graft function and patient mortality.RESULTS In this study,307(22.4%)and 394(29.6%)KTRs had 30-d and 90-d EHRs,respectively.Factors such as having previous cases of rejection,being transplanted in more recent years,having a longer duration of dialysis pretransplant,and having an expanded criteria donor were associated with EHR post-transplant.The cumulative probability of death censored graft failure,as well as total graft failure,was higher among the 90-d EHR group as compared to patients with no EHR.While multivariable models found no significant association between EHR and patient mortality,patients with EHR were at an increased risk of late hospital readmissions,poorer kidney function throughout the 1st year post-transplant,and higher hospital-based care costs within the 1st year of follow-up.CONCLUSION EHRs are associated with suboptimal outcomes after kidney transplant and increased financial burden on the healthcare system.The results warrant the need for effective strategies to reduce post-transplant EHR.展开更多
Objective To investigate the role of peripheral lymphocytes Sialyl Lewis(x) (CD15s) antigen before and after kidney transplantation. Methods Flow cytometry technique was applied to examine the expression of peripheral...Objective To investigate the role of peripheral lymphocytes Sialyl Lewis(x) (CD15s) antigen before and after kidney transplantation. Methods Flow cytometry technique was applied to examine the expression of peripheral lymphoid cell surface CD15s antigen after renal transplantation, and to evaluate various therapeutic regimen. Results The statistic analysis results of peripheral lymphoid cell surface CD15s antigen expression level showed that there was significant difference among the patients with acute rejection, long-term dialysis and with normal renal function post-transplant; significant difference of CD15s expression level between group of rejection and infection; no significant difference of CD15s expression among the different groups treated by various therapeutic regimens. Conclusion The different therapeutic regimen has no influence to CD15s expression; Detection of peripheral lymphoid cell surface CD15s antigen expression periodically, intelligently make convenience to understand suitable status of immunosuppression.展开更多
BK virus(BKV) is a polyomavirus that is able to cause renal dysfunction in transplanted grafts via BK virusassociated nephritis(BKVAN).This condition was misdiagnosed in the past due to clinical and histopthological s...BK virus(BKV) is a polyomavirus that is able to cause renal dysfunction in transplanted grafts via BK virusassociated nephritis(BKVAN).This condition was misdiagnosed in the past due to clinical and histopthological similarities with acute rejection.Due to the prevalence of the virus in the population,it is an important pathogen in this context,and so it is important to understand how this virus functions and its' relationship with the pathogenesis of BKVN.Screening for BKV often reveals viruria and/or viremia,which then manifests as BKVN,which can be asymptomatic or result in clinical features namely renal dysfunction.The pathogenesis of BKV infection is still unclear and needs to be further investigated; nevertheless there are a variety of hypotheses that indicate that there are a host of factors that play important roles.Treatments for BKVAN include a reduction in immunosuppression,the use of antiviral therapy or the combination of both treatment options.展开更多
BACKGROUND Post-transplant lymphoproliferative disease(PTLD)is the most common malignant tumor that occurs after kidney transplantation in children,and is associated with Epstein-Barr virus(EBV).CASE SUMMARY We report...BACKGROUND Post-transplant lymphoproliferative disease(PTLD)is the most common malignant tumor that occurs after kidney transplantation in children,and is associated with Epstein-Barr virus(EBV).CASE SUMMARY We report a case of PTLD that occurred in a 17-year-old female patient at 5 mo post-transplant.The first symptom was abdominal pain accompanied by fever,nausea,and vomiting.EBV-associated monomorphic PTLD with multiple abdominal nodules was diagnosed by pathology,clinical manifestations,imaging results,and the presence of EB-DNA.After successful treatment with rituximab,the abdominal nodules in the spleen and liver disappeared.CONCLUSION Early pathological biopsy to confirm the diagnosis is critical to treatment and prognosis.Reducing immunosuppression and rituximab therapy are effective methods for treating PTLD,but need to be initiated as early as possible.展开更多
Objective:To investigate the clinical application of sirolimus (SRL) in renal post-transplant which included sirolimus in place of mycophenolate mofetil. Their clinical course was evaluated during the first 6 months a...Objective:To investigate the clinical application of sirolimus (SRL) in renal post-transplant which included sirolimus in place of mycophenolate mofetil. Their clinical course was evaluated during the first 6 months after surgery. Maintenance immunosuppression included sirolimus, corticosteroid and cyclosporine. Sirolimus dosing was initiated at 6 mg on the first day, from then on 1.2-1.5 mg as a single daily dose and adjusted to maintain the levels at 5-15 ng/ml. 25 cases were treated with SRL combined group). Results: Patients' graft survival rate was 100％. There was no significant difference in average serum creatinine level and incidence of acute rejection between SRL group and MMF group[10.0％ (2/20)vs 11.4％ (4/35), P＞0. 05]. During the follow-up period, the incidence of side effect was similar in SRL group or MMF group, except for hyperlipidemia in SRL group. Sirolimus was discontinued in 5 patients for adverse events predominantly for numbness of oral lip, delayed renal allograft function, poor wound healing, liver or kidney function injury and pneumonitis. Conclusion: Early outcomes with sirolimus were acceptable with 100％ graft survival and 10. 0％ incidence of acute rejection. However, because of adverse events including poor wound healing and pneumonitis, the immunosuppression regimen of SRL combined with low dose of CsA has been limited to clinical application in some degree in early transplant recipients. As one of therapeutical choices, it has been a long way to investigate SRL in clinical extension.展开更多
Objective:To explore the peculiarities of kidney transplantation in elderly patients and define the perioperative managements. Methods: The clinical data of kidney transplantation in 29 patients older than 65years wer...Objective:To explore the peculiarities of kidney transplantation in elderly patients and define the perioperative managements. Methods: The clinical data of kidney transplantation in 29 patients older than 65years were reviewed, the eldest being 84 years old and the mean age 68. 1 years. Results: Four episodes of acute rejection (13. 80%) were encountered. FK506 toxicity occurred in one case (3.40%) and lung infection in another (3.40%), who (along with the former 4 patients) all were cured subsequently. In one case, the kidney graft was removed for thrombogenesis of the renal artery. The 1- and 3-year patients/grafts survival of 100% and 96.5% respectively was achieved, with the longest survival exceeding 5 years. Conclusions:Old age was not the absolute contraindication for kidney transplantation. Strict observance of the indications of kidney transplantation and donor selection with well-matched tissue-typing are crucial in elderly patients.Adequate application of immunosuppressants and effective long-term follow-up are also major factors for long-term allograft survival.展开更多
Triggering receptor expressed on myeloid cells-1(TREM-1)is a member of the immunoglobulin superfamily.As an amplifier of the inflammatory response,TREM-1 is mainly involved in the production of inflammatory mediators ...Triggering receptor expressed on myeloid cells-1(TREM-1)is a member of the immunoglobulin superfamily.As an amplifier of the inflammatory response,TREM-1 is mainly involved in the production of inflammatory mediators and the regulation of cell survival.TREM-1 has been studied in infectious diseases and more recently in non-infectious disorders.More and more studies have shown that TREM-1 plays an important pathogenic role in kidney diseases.There is evidence that TREM-1 can not only be used as a biomarker for diagnosis of disease but also as a potential therapeutic target to guide the development of novel therapeutic agents for kidney disease.This review summarized molecular biology of TREM-1 and its signaling pathways as well as immune response in the progress of acute kidney injury,renal fibrosis,diabetic nephropathy,immune nephropathy,and renal cell carcinoma.展开更多
BACKGROUND Endoscopic retrograde cholangiopancreatography(ERCP)is a key procedure for diagnosing and treating biliary and pancreatic disorders.Although effective,it carries risks,including rare but severe complication...BACKGROUND Endoscopic retrograde cholangiopancreatography(ERCP)is a key procedure for diagnosing and treating biliary and pancreatic disorders.Although effective,it carries risks,including rare but severe complications such as air embolism.CASE SUMMARY We report a case of a 58-year-old man who developed extensive air embolism during ERCP.He previously underwent a Whipple procedure and experienced a sudden drop in vital signs and loss of consciousness.Immediate intervention with hyperbaric oxygen therapy and supportive care led to gradual recovery.Imaging confirmed widespread air embolism,which resolved with continued treatment.CONCLUSION Air embolism is a rare,critical complication of ERCP,especially in patients with prior surgery such as pancreaticoduodenectomy.Early detection and prompt treatment,including hyperbaric oxygen therapy,are crucial for favorable out-comes.展开更多
To the Editor:Ureterostenosis is one of the most common complications after kidney transplantation,with an incidence rate of 1.0–8.3%according to a relevant report.[1,2]This complication may cause postrenal obstructi...To the Editor:Ureterostenosis is one of the most common complications after kidney transplantation,with an incidence rate of 1.0–8.3%according to a relevant report.[1,2]This complication may cause postrenal obstruction,affecting the function of the transplanted kidney and increasing the risk of kidney loss.展开更多
BACKGROUND Pelvic lipomatosis is a rare disease of unknown etiology,characterized by the overgrowth of pelvic adipose tissue that causes compression of the urinary tract including the bladder and ureters,rectum and bl...BACKGROUND Pelvic lipomatosis is a rare disease of unknown etiology,characterized by the overgrowth of pelvic adipose tissue that causes compression of the urinary tract including the bladder and ureters,rectum and blood vessels.The patient may progressively develop obstructive uropathy which could subsequently lead to renal failure.At present,there are no reports of renal transplantation due to uremia caused by pelvic lipomatosis.The ideal management of patients with pelvic lipomatosis after renal transplantation is not yet well-established due to the lack of literature and follow-up data.CASE SUMMARY We report a 37-year-old male patient with pelvic lipomatosis who received a successful living donor renal transplantation on July 22,2015.The operation was complicated as the iliac vessels and bladder were wrapped entirely in excessive abnormal fat.The external iliac artery and vein were located using ultrasonographic guidance.The adipose tissue around the right bladder was removed as far as possible,and the graft ureter was reimplanted into the bladder,using the Lich-Gregoir technique.At 22 mo after transplantation,graft percutaneous nephrostomy was performed under ultrasonographic guidance for urinary diversion due to hydronephrosis of the graft kidney.Follow-up at four years showed that the renal allograft function was stable.CONCLUSION When patients with pelvic lipomatosis develop renal failure,renal transplantation could be a feasible treatment strategy.展开更多
Objective: To study the effect of tacrolimus (Prograf, FK506) in preventing renal allograft rejection. Methods: The curative effect, therapy index, toxicity and side effects of FK506 were observed in 294renal transpla...Objective: To study the effect of tacrolimus (Prograf, FK506) in preventing renal allograft rejection. Methods: The curative effect, therapy index, toxicity and side effects of FK506 were observed in 294renal transplant recipients among whom 268 received FK506 24 h after the operation and the other 26 with cyclosporine (CsA) developed acute rejection after transplantation and were given FK506 to replace methylprednisolone (MP) when the latter did not result. All the patients were given oral mycophenolate mofetil (MMF, 1.0 g/d) and meticorten (Pred, 30 mg/d) 24 h later after operation. Results: In the 268 recipients previously mentioned, the incidence of acute rejection was 10. 45%, glycometabolism disorder 9.33%, nervous system disturbance 1.59%, liver function abnormality 2.99%, nephrotoxicity 1.87%, gastrointestinal disorder 17. 5%, cytomegalovirus (CMV) viremia 2.99%, and non-CMV pulmonary infection 1. 59%(4/268), with 1 fatal case for cerebral hemorrhage with normal allograft function and another 2 non-fatal cases in which function loss resulted in removal of the allografts. The blood trough concentrations of FK506were between 5 and 20μg/L. In the 26 cases of steroid-resistant rejection, 23 (88. 46%, 23/26) were reversed and the rest 3 required plasma exchange and application of OKT3 before recovery. Conclusion: As a safe and effective immunosuppressant, FK506 can reduce the incidence of allograft rejection in kidney transplant recipients with little side effects or toxicity, which is particularly applicable in patients with steroid-resistant rejection or CsA nephrotoxicity. Attention should to be paid to glycometabolism disorder due to FK506, however, the long-term effects of FK506 need further investigation.展开更多
Objective:To study the effect of mechanism of high glucose on apoptosis and cell cycle arrest of isletβcells via p27 pathway.Methods:Islet INS-1 cells were cultured and divided into groups.The control group was treat...Objective:To study the effect of mechanism of high glucose on apoptosis and cell cycle arrest of isletβcells via p27 pathway.Methods:Islet INS-1 cells were cultured and divided into groups.The control group was treated with ordinary medium,the high glucose group was treated with high glucose medium containing 25mmol/L glucose,the high glucose+si-NC group was treated with high glucose medium and transfected with NC siRNA,and the high glucose+si-P27 group was treated with high glucose medium and transfected with p27 siRNA.After 24 hours treatment,MTS assay was used to detect the cell viability A490,TUNEL assay was used to detect apoptosis rate,flow cytometry was used to detect the cell cycle distribution and western blot was used to detect the expression levels of P27,caspase-8 and cyclinD1.Results:Compared with those in the control group,the A490,the ratio of S phase and G2/M phase as well as the expression level of CyclinD1 decreased,while the apoptosis rate,the ratio of G0/G1 phase as well as the expression levels of P27 and caspase-8 increased in the high glucose group(P<0.05);compared with those in the high glucose group,the A490,cell cycle as well as the expression levels of P27,caspase-8 and cyclinD1 were not different from those in the high glucose+si-NC group(P>0.05);compared with those in the high glucose group and high glucose+si-NC group,the A490,the ratio of S phase and G2/M phase as well as the expression levels of cyclinD1 increased,while the apoptosis rate,the ratio of G0/G1 phase as well as the expression levels of p27 and caspase-8 decreased in the high glucose+si-P27 group(P<0.05).Conclusion:The apoptosis and cell cycle arrest induced by high glucose are related to P27 pathway activation.展开更多
BACKGROUND Immature dendritic cells(imDCs)play an important role in the induction of donor-specific transplant immunotolerance.However,these cells have limitations,such as rapid maturation and a short lifespan in vivo...BACKGROUND Immature dendritic cells(imDCs)play an important role in the induction of donor-specific transplant immunotolerance.However,these cells have limitations,such as rapid maturation and a short lifespan in vivo.In previous studies,induced pluripotent stem cells(iPSCs)differentiated into imDCs,and sinomenine(SN)was used to inhibit the maturation of imDCs.AIM To study the capacity of SN to maintain iPSC-derived imDCs(SN-iPSCs-imDCs)in an immature state and the mechanism by which SN-iPSCs-imDCs induce immunotolerance.METHODS In this study,mouse iPSCs were induced to differentiate into imDCs in culture medium without or with SN(iPSCs-imDCs and SN-iPSCs-imDCs).The imDCrelated surface markers,endocytotic capacity of fluorescein isothiocyanate Dextran and apoptosis were analyzed by flow cytometry.The effects of iPSCs-imDCs and SNiPSCs-imDCs on T-cell stimulatory function,and regulatory T(Treg)cell proliferative function in vitro were analyzed by mixed lymphocyte reaction.Cytokine expression was detected by ELISA.The apoptosis-related proteins of iPSCs-DCs and SN-iPSCs-DCs were analyzed by western blotting.The induced immunotolerance of SN-iPSCs-DCs was evaluated by treating recipient Balb/c skin graft mice.Statistical evaluation of graft survival was performed using Kaplan–Meier curves.RESULTS Both iPSCs-imDCs and SN-iPSCs-imDCs were successfully obtained,and their biological characteristics and ability to induce immunotolerance were compared.SN-iPSCs-imDCs exhibited higher CD11c levels and lower CD80 and CD86 levels compared with iPSCs-imDCs.Reduced major histocompatibility complex II expression,worse T-cell stimulatory function,higher Treg cell proliferative function and stronger endocytotic capacity were observed with SN-iPSCs-imDCs(P<0.05).The levels of interleukin(IL)-2,IL-12,interferon-γin SN-iPSCs-imDCs were lower than those in iPSCs-imDCs,whereas IL-10 and transforming growth factor-βlevels were higher(P<0.05).The apoptosis rate of these cells was significantly higher(P<0.05),and the expression levels of cleaved caspase3,Bax and cleaved poly(ADP-ribose)polymerase were higher after treatment with lipopolysaccharides,but Bcl-2 was reduced.In Balb/c mice recipients immunized with iPSCsimDCs or SN-iPSCs-imDCs 7 d before skin grafting,the SN-iPSCs-imDCs group showed lower ability to inhibit donor-specific CD4+T-cell proliferation(P<0.05)and a higher capacity to induce CD4+CD25+FoxP3+Treg cell proliferation in the spleen(P<0.05).The survival span of C57bl/6 skin grafts was significantly prolonged in immunized Balb/c recipients with a donor-specific pattern.CONCLUSION This study demonstrated that SN-iPSCs-imDCs have potential applications in vitro and in vivo for induction of immunotolerance following organ transplantation.展开更多
Objective： To set up a method for isolation and culture of mature Sertoli cells and to estimate their effects on allogeneic islets cocultured in vitro. Methods： Adult SD rat testicular Sertoli cells were prepared su...Objective： To set up a method for isolation and culture of mature Sertoli cells and to estimate their effects on allogeneic islets cocultured in vitro. Methods： Adult SD rat testicular Sertoli cells were prepared successfully by three-step enzyme digestion. Then they were cocultured respectively with allogeneic islets and activated Wistar rat splenocytes. 24-hour cumulative insulin release and glucose-stimulated insulin secretion test were performed to detect islet function between pure islets culture group and coculture group. Splenocyte proliferation activity was determined by MTT colorimetry assay to observe the inhibition effect of Sertoli cells in different densities. Result： Firstly, in pure islet culture group, the 24-hour cumulative insulin release was gradually decreased in 21-day culture time. Compared to day 3, this change was significant on day 7 （P 〈 0.05） and on day 10,14,21 （P 〈 0.01）. In contrast, in coculture group, compared to day 3, the 24-hour cumulative insulin release was increased significantly on day 7 （P 〈 0.01 ）, and then gradually decreased on day 10 and 14, but still higher than that of day 3. It was on day 21 that it began to decrease compared to day 3 （P 〈 0.05）. During the culture time in vitro, the 24-hour cumulative insulin release of islet coculture group was significantly higher than that of pure islets culture group （P 〈 0.01）. In the case of stimulation index（SI）, there was a similar tendency as insulin release in the two groups. Secondly, mature Sertoli cells（1×10^6/mL） pretreated by 15 grays irradiation could decrease proliferation activity of activated splenocytes compared to that of control group （P 〈 0.01 ）. This inhibition effect was dose-dependent. Conclusion： Mature Sertoli cells can improve the function and prolong the survival of islet cells cultured in vitro. They can also provide an immune protection to islet cells. The approach described above might be applicable to human islet transplantation as soon as if it is also valid in large animal models.展开更多
Background:Delayed graft function(DGF)is the main cause of renal function failure after kidney transplantation.This study aims at investigating the value of hypothermic machine perfusion(HMP)parameters combined with p...Background:Delayed graft function(DGF)is the main cause of renal function failure after kidney transplantation.This study aims at investigating the value of hypothermic machine perfusion(HMP)parameters combined with perfusate biomarkers on predicting DGF and the time of renal function recovery after deceased donor(DD)kidney transplantation.Methods:HMP parameters,perfusate biomarkers and baseline characteristics of 113 DD kidney transplantations from January 1,2019 to August 31,2019 in the First Affiliated Hospital of Xi’an Jiaotong University were retrospectively analyzed using univariate and multivariate logistic regression analysis.Results:In this study,the DGF incidence was 17.7%(20/113);The multivariate logistic regression results showed that terminal resistance(OR:1.879,95%CI 1.145-3.56)and glutathione S-transferase(GST)(OR=1.62,95%CI 1.23-2.46)were risk factors for DGF;The Cox model analysis indicated that terminal resistance was an independent hazard factor for renal function recovery time(HR=0.823,95%CI 0.735-0.981).The model combining terminal resistance and GST(AUC=0.888,95%CI:0.842-0.933)significantly improved the DGF predictability compared with the use of terminal resistance(AUC=0.756,95%CI 0.693-0.818)or GST alone(AUC=0.729,95%CI 0.591-0.806).Conclusion:According to the factors analyzed in this study,the combination of HMP parameters and perfusate biomarkers displays a potent DGF predictive value.展开更多
Background: Hypothermic machine perfusion(HMP) is being used more often in cardiac death kidney transplantation; however, the significance of assessing organ quality and predicting delayed graft function(DGF) by HMP p...Background: Hypothermic machine perfusion(HMP) is being used more often in cardiac death kidney transplantation; however, the significance of assessing organ quality and predicting delayed graft function(DGF) by HMP parameters is still controversial. Therefore,we used a readily available HMP variable to design a scoring model that can identify the highest risk of DGF and provide the guidance and advice for organ allocation and DCD kidney assessment.Methods: From September 1, 2012 to August 31, 2016, 366 qualified kidneys were randomly assigned to the development and validation cohorts in a 2:1 distribution. The HMP variables of the development cohort served as candidate univariate predictors for DGF. The independent predictors of DGF were identified by multivariate logistic regression analysis with a P < 0.05. According to the odds ratios(ORs) value, each HMP variable was assigned a weighted integer, and the sum of the integers indicated the total risk score for each kidney. The validation cohort was used to verify the accuracy and reliability of the scoring model.Results: HMP duration(OR = 1.165, 95% confidence interval [CI ]: 1.008–1.360, P = 0.043), resistance(OR = 2.190, 95%CI: 1.032–10.20, P < 0.001), and flow rate(OR = 0.931, 95% CI: 0.894–0.967, P = 0.011) were the independent predictors of identified DGF. The HMP predictive score ranged from 0 to 14, and there was a clear increase in the incidence of DGF, from the low predictive score group to the very high predictive score group. We formed four increasingly serious risk categories(scores 0–3, 4–7, 8–11, and 12–14)according to the frequency associated with the different risk scores of DGF. The HMP predictive score indicates good discriminative power with a c?statistic of 0.706 in the validation cohort, and it had significantly better prediction value for DGF compared to both terminal flow(P = 0.012) and resistance(P = 0.006).Conclusion: The HMP predictive score is a good noninvasive tool for assessing the quality of DCD kidneys, and it is potentially useful for physicians in making optimal decisions about the organs donated.展开更多
Modulation of alloimmune responses is critical to improving transplant outcome and promoting long-term graft survival.To determine mechanisms by which a nonhematopoietic erythropoietin(EPO)derivative,carbamylated EPO(...Modulation of alloimmune responses is critical to improving transplant outcome and promoting long-term graft survival.To determine mechanisms by which a nonhematopoietic erythropoietin(EPO)derivative,carbamylated EPO(CEPO),regulates innate and adaptive immune cells and affects renal allograft survival,we utilized a rat model of fully MHC-mismatched kidney transplantation.CEPO administration markedly extended the survival time of kidney allografts compared with the transplant alone control group.This therapeutic effect was inhibited when the recipients were given LY294002,a selective inhibitor of the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway or anti-EPO receptor(EPOR)antibody,in addition to CEPO.In vitro,CEPO inhibited the differentiation and function of dendritic cells and modulated their production of proinflammatory and anti-inflammatory cytokines,along with activating the PI3K/AKT signaling pathway and increasing EPOR mRNA and protein expression by these innate immune cells.Moreover,after CD4^(+)T cells were exposed to CEPO the Th1/Th2 ratio decreased and the regulatory T cell(Treg)/Th17 ratio increased.These effects were abolished by LY294002 or anti-EPOR antibody,suggesting that CEPO regulates immune responses and promotes kidney allograft survival by activating the PI3K/AKT signaling pathway in an EPOR-dependent manner.The immunomodulatory and specific signaling pathway effects of CEPO identified in this study suggest a potential therapeutic approach to promoting kidney transplant survival.展开更多
基金This work was supported by the Natural Science Foundation of Hunan Province,China (2024JJ9201)。
文摘Objective:Compared with long-term renal replacement therapy,kidney transplantation is the ideal treatment for end-stage renal disease(ESRD),significantly extending patient life and improving quality of life.Kidney transplant patients need to adhere to lifelong immunosuppressive medication regimens,but their medication adherence is generally poor compared with other organ transplant recipients.Medication adherence is closely related to medication literacy and psychological status,yet related studies are limited.This study aims to investigate the current status of medication adherence,inner strength,and medication literacy in kidney transplant patients,analyze the relationships among these 3 factors,and explore the mediating role of inner strength in the relationship between medication literacy and medication adherence.Methods:A cross-sectional survey was conducted from March to October 2023 involving 421 patients aged≥18 years who visited kidney transplantation outpatient clinics at 4 tertiary hospitals in Hunan Province.The inner strength,medication literacy,and medication adherence of kidney transplant patients were investigated using the Inner Strength Scale(ISS),the Chinese version of the Medication Literacy Assessment in Spanish and English(MedLitRxSE),and the Chinese version of the Morisky Medication Adherence Scale-8(C-MMAS-8),respectively.Univariate analysis was performed to examine the effects of demographic and clinical data on medication adherence.Correlation analysis was conducted to explore the relationships among medication literacy,medication adherence,and inner strength.Significant variables from univariate and correlation analyses were further analyzed using multiple linear regression,and the mediating effect of inner strength was explored.Results:Among the 421 questionnaires collected,408 were valid,with an effective rate of 96.91%.The scores of C-MMAS-8,MedLitRxSE,and ISS were 6.64±1.16,100.63±14.67,and 8.47±4.03,respectively.Among the 408 patients,only 86(21.08%)patients had a high level of medication adherence,whereas 230(56.37%)patients had a medium level of medication adherence,and 92(22.55%)patients had poor medication adherence.Univariate analysis indicated that the kidney transplant patients’age,marital status,education levels,years since their kidney transplant operation,number of hospitalizations after the kidney transplant,and adverse drug reactions showed significant differences in medication adherence(all P<0.05).Correlation analysis showed that inner strength positively correlated with both medication literacy(r=0.183,P<0.001)and medication adherence(r=0.201,P<0.001).Additionally,there was a positive correlation between medication adherence and medication literacy(r=0.236,P<0.001).Inner strength accounted for 13.22%of the total effect in the mediating role between medication literacy and medication adherence.Conclusion:The level of medication adherence among kidney transplant patients needs improvement,and targeted intervention measures are essential.Inner strength mediates the relationship between medication literacy and medication adherence in these patients.Healthcare professionals should focus on enhancing medication literacy and supporting patients’inner strength to improve medication adherence.
基金The study was reviewed and approved by the University Health Network Institutional Review Board.
文摘BACKGROUND Early hospital readmissions(EHRs)after kidney transplantation range in incidence from 18%-47%and are important and substantial healthcare quality indicators.EHR can adversely impact clinical outcomes such as graft function and patient mortality as well as healthcare costs.EHRs have been extensively studied in American healthcare systems,but these associations have not been explored within a Canadian setting.Due to significant differences in the delivery of healthcare and patient outcomes,results from American studies cannot be readily applicable to Canadian populations.A better understanding of EHR can facilitate improved discharge planning and long-term outpatient management post kidney transplant.AIM To explore the burden of EHR on kidney transplant recipients(KTRs)and the Canadian healthcare system in a large transplant centre.METHODS This single centre cohort study included 1564 KTRs recruited from January 1,2009 to December 31,2017,with a 1-year follow-up.We defined EHR as hospitalizations within 30 d or 90 d of transplant discharge,excluding elective procedures.Multivariable Cox and linear regression models were used to examine EHR,late hospital readmissions(defined as hospitalizations within 31-365 d for 30-d EHR and within 91-365 d for 90-d EHR),and outcomes including graft function and patient mortality.RESULTS In this study,307(22.4%)and 394(29.6%)KTRs had 30-d and 90-d EHRs,respectively.Factors such as having previous cases of rejection,being transplanted in more recent years,having a longer duration of dialysis pretransplant,and having an expanded criteria donor were associated with EHR post-transplant.The cumulative probability of death censored graft failure,as well as total graft failure,was higher among the 90-d EHR group as compared to patients with no EHR.While multivariable models found no significant association between EHR and patient mortality,patients with EHR were at an increased risk of late hospital readmissions,poorer kidney function throughout the 1st year post-transplant,and higher hospital-based care costs within the 1st year of follow-up.CONCLUSION EHRs are associated with suboptimal outcomes after kidney transplant and increased financial burden on the healthcare system.The results warrant the need for effective strategies to reduce post-transplant EHR.
基金This work was supported by the Xi'an Jiaotong University Doctor Fund (No.y100.011005)
文摘Objective To investigate the role of peripheral lymphocytes Sialyl Lewis(x) (CD15s) antigen before and after kidney transplantation. Methods Flow cytometry technique was applied to examine the expression of peripheral lymphoid cell surface CD15s antigen after renal transplantation, and to evaluate various therapeutic regimen. Results The statistic analysis results of peripheral lymphoid cell surface CD15s antigen expression level showed that there was significant difference among the patients with acute rejection, long-term dialysis and with normal renal function post-transplant; significant difference of CD15s expression level between group of rejection and infection; no significant difference of CD15s expression among the different groups treated by various therapeutic regimens. Conclusion The different therapeutic regimen has no influence to CD15s expression; Detection of peripheral lymphoid cell surface CD15s antigen expression periodically, intelligently make convenience to understand suitable status of immunosuppression.
文摘BK virus(BKV) is a polyomavirus that is able to cause renal dysfunction in transplanted grafts via BK virusassociated nephritis(BKVAN).This condition was misdiagnosed in the past due to clinical and histopthological similarities with acute rejection.Due to the prevalence of the virus in the population,it is an important pathogen in this context,and so it is important to understand how this virus functions and its' relationship with the pathogenesis of BKVN.Screening for BKV often reveals viruria and/or viremia,which then manifests as BKVN,which can be asymptomatic or result in clinical features namely renal dysfunction.The pathogenesis of BKV infection is still unclear and needs to be further investigated; nevertheless there are a variety of hypotheses that indicate that there are a host of factors that play important roles.Treatments for BKVAN include a reduction in immunosuppression,the use of antiviral therapy or the combination of both treatment options.
文摘BACKGROUND Post-transplant lymphoproliferative disease(PTLD)is the most common malignant tumor that occurs after kidney transplantation in children,and is associated with Epstein-Barr virus(EBV).CASE SUMMARY We report a case of PTLD that occurred in a 17-year-old female patient at 5 mo post-transplant.The first symptom was abdominal pain accompanied by fever,nausea,and vomiting.EBV-associated monomorphic PTLD with multiple abdominal nodules was diagnosed by pathology,clinical manifestations,imaging results,and the presence of EB-DNA.After successful treatment with rituximab,the abdominal nodules in the spleen and liver disappeared.CONCLUSION Early pathological biopsy to confirm the diagnosis is critical to treatment and prognosis.Reducing immunosuppression and rituximab therapy are effective methods for treating PTLD,but need to be initiated as early as possible.
文摘Objective:To investigate the clinical application of sirolimus (SRL) in renal post-transplant which included sirolimus in place of mycophenolate mofetil. Their clinical course was evaluated during the first 6 months after surgery. Maintenance immunosuppression included sirolimus, corticosteroid and cyclosporine. Sirolimus dosing was initiated at 6 mg on the first day, from then on 1.2-1.5 mg as a single daily dose and adjusted to maintain the levels at 5-15 ng/ml. 25 cases were treated with SRL combined group). Results: Patients' graft survival rate was 100％. There was no significant difference in average serum creatinine level and incidence of acute rejection between SRL group and MMF group[10.0％ (2/20)vs 11.4％ (4/35), P＞0. 05]. During the follow-up period, the incidence of side effect was similar in SRL group or MMF group, except for hyperlipidemia in SRL group. Sirolimus was discontinued in 5 patients for adverse events predominantly for numbness of oral lip, delayed renal allograft function, poor wound healing, liver or kidney function injury and pneumonitis. Conclusion: Early outcomes with sirolimus were acceptable with 100％ graft survival and 10. 0％ incidence of acute rejection. However, because of adverse events including poor wound healing and pneumonitis, the immunosuppression regimen of SRL combined with low dose of CsA has been limited to clinical application in some degree in early transplant recipients. As one of therapeutical choices, it has been a long way to investigate SRL in clinical extension.
文摘Objective:To explore the peculiarities of kidney transplantation in elderly patients and define the perioperative managements. Methods: The clinical data of kidney transplantation in 29 patients older than 65years were reviewed, the eldest being 84 years old and the mean age 68. 1 years. Results: Four episodes of acute rejection (13. 80%) were encountered. FK506 toxicity occurred in one case (3.40%) and lung infection in another (3.40%), who (along with the former 4 patients) all were cured subsequently. In one case, the kidney graft was removed for thrombogenesis of the renal artery. The 1- and 3-year patients/grafts survival of 100% and 96.5% respectively was achieved, with the longest survival exceeding 5 years. Conclusions:Old age was not the absolute contraindication for kidney transplantation. Strict observance of the indications of kidney transplantation and donor selection with well-matched tissue-typing are crucial in elderly patients.Adequate application of immunosuppressants and effective long-term follow-up are also major factors for long-term allograft survival.
基金supported by grants from the National Natural Science Foundation of China(Nos.82070776,82270796,82200849,and 82370761)the Science and Technology Innovation Program of Hunan Province(No.2022RC3071)+1 种基金the Natural Science Foundation of Hunan Province(No.2023JJ40872)the Higher Education Teaching Reform Project of Central South University(No.2023jy110).
文摘Triggering receptor expressed on myeloid cells-1(TREM-1)is a member of the immunoglobulin superfamily.As an amplifier of the inflammatory response,TREM-1 is mainly involved in the production of inflammatory mediators and the regulation of cell survival.TREM-1 has been studied in infectious diseases and more recently in non-infectious disorders.More and more studies have shown that TREM-1 plays an important pathogenic role in kidney diseases.There is evidence that TREM-1 can not only be used as a biomarker for diagnosis of disease but also as a potential therapeutic target to guide the development of novel therapeutic agents for kidney disease.This review summarized molecular biology of TREM-1 and its signaling pathways as well as immune response in the progress of acute kidney injury,renal fibrosis,diabetic nephropathy,immune nephropathy,and renal cell carcinoma.
文摘BACKGROUND Endoscopic retrograde cholangiopancreatography(ERCP)is a key procedure for diagnosing and treating biliary and pancreatic disorders.Although effective,it carries risks,including rare but severe complications such as air embolism.CASE SUMMARY We report a case of a 58-year-old man who developed extensive air embolism during ERCP.He previously underwent a Whipple procedure and experienced a sudden drop in vital signs and loss of consciousness.Immediate intervention with hyperbaric oxygen therapy and supportive care led to gradual recovery.Imaging confirmed widespread air embolism,which resolved with continued treatment.CONCLUSION Air embolism is a rare,critical complication of ERCP,especially in patients with prior surgery such as pancreaticoduodenectomy.Early detection and prompt treatment,including hyperbaric oxygen therapy,are crucial for favorable out-comes.
文摘To the Editor:Ureterostenosis is one of the most common complications after kidney transplantation,with an incidence rate of 1.0–8.3%according to a relevant report.[1,2]This complication may cause postrenal obstruction,affecting the function of the transplanted kidney and increasing the risk of kidney loss.
基金Supported by National Natural Science Foundation of China,No.81970654。
文摘BACKGROUND Pelvic lipomatosis is a rare disease of unknown etiology,characterized by the overgrowth of pelvic adipose tissue that causes compression of the urinary tract including the bladder and ureters,rectum and blood vessels.The patient may progressively develop obstructive uropathy which could subsequently lead to renal failure.At present,there are no reports of renal transplantation due to uremia caused by pelvic lipomatosis.The ideal management of patients with pelvic lipomatosis after renal transplantation is not yet well-established due to the lack of literature and follow-up data.CASE SUMMARY We report a 37-year-old male patient with pelvic lipomatosis who received a successful living donor renal transplantation on July 22,2015.The operation was complicated as the iliac vessels and bladder were wrapped entirely in excessive abnormal fat.The external iliac artery and vein were located using ultrasonographic guidance.The adipose tissue around the right bladder was removed as far as possible,and the graft ureter was reimplanted into the bladder,using the Lich-Gregoir technique.At 22 mo after transplantation,graft percutaneous nephrostomy was performed under ultrasonographic guidance for urinary diversion due to hydronephrosis of the graft kidney.Follow-up at four years showed that the renal allograft function was stable.CONCLUSION When patients with pelvic lipomatosis develop renal failure,renal transplantation could be a feasible treatment strategy.
文摘Objective: To study the effect of tacrolimus (Prograf, FK506) in preventing renal allograft rejection. Methods: The curative effect, therapy index, toxicity and side effects of FK506 were observed in 294renal transplant recipients among whom 268 received FK506 24 h after the operation and the other 26 with cyclosporine (CsA) developed acute rejection after transplantation and were given FK506 to replace methylprednisolone (MP) when the latter did not result. All the patients were given oral mycophenolate mofetil (MMF, 1.0 g/d) and meticorten (Pred, 30 mg/d) 24 h later after operation. Results: In the 268 recipients previously mentioned, the incidence of acute rejection was 10. 45%, glycometabolism disorder 9.33%, nervous system disturbance 1.59%, liver function abnormality 2.99%, nephrotoxicity 1.87%, gastrointestinal disorder 17. 5%, cytomegalovirus (CMV) viremia 2.99%, and non-CMV pulmonary infection 1. 59%(4/268), with 1 fatal case for cerebral hemorrhage with normal allograft function and another 2 non-fatal cases in which function loss resulted in removal of the allografts. The blood trough concentrations of FK506were between 5 and 20μg/L. In the 26 cases of steroid-resistant rejection, 23 (88. 46%, 23/26) were reversed and the rest 3 required plasma exchange and application of OKT3 before recovery. Conclusion: As a safe and effective immunosuppressant, FK506 can reduce the incidence of allograft rejection in kidney transplant recipients with little side effects or toxicity, which is particularly applicable in patients with steroid-resistant rejection or CsA nephrotoxicity. Attention should to be paid to glycometabolism disorder due to FK506, however, the long-term effects of FK506 need further investigation.
基金National Natural Science Foundation of China(No.81970668)Shaanxi Science and Technology Planning Project(No.2019JM-116)。
文摘Objective:To study the effect of mechanism of high glucose on apoptosis and cell cycle arrest of isletβcells via p27 pathway.Methods:Islet INS-1 cells were cultured and divided into groups.The control group was treated with ordinary medium,the high glucose group was treated with high glucose medium containing 25mmol/L glucose,the high glucose+si-NC group was treated with high glucose medium and transfected with NC siRNA,and the high glucose+si-P27 group was treated with high glucose medium and transfected with p27 siRNA.After 24 hours treatment,MTS assay was used to detect the cell viability A490,TUNEL assay was used to detect apoptosis rate,flow cytometry was used to detect the cell cycle distribution and western blot was used to detect the expression levels of P27,caspase-8 and cyclinD1.Results:Compared with those in the control group,the A490,the ratio of S phase and G2/M phase as well as the expression level of CyclinD1 decreased,while the apoptosis rate,the ratio of G0/G1 phase as well as the expression levels of P27 and caspase-8 increased in the high glucose group(P<0.05);compared with those in the high glucose group,the A490,cell cycle as well as the expression levels of P27,caspase-8 and cyclinD1 were not different from those in the high glucose+si-NC group(P>0.05);compared with those in the high glucose group and high glucose+si-NC group,the A490,the ratio of S phase and G2/M phase as well as the expression levels of cyclinD1 increased,while the apoptosis rate,the ratio of G0/G1 phase as well as the expression levels of p27 and caspase-8 decreased in the high glucose+si-P27 group(P<0.05).Conclusion:The apoptosis and cell cycle arrest induced by high glucose are related to P27 pathway activation.
基金Supported by National Natural Science Foundation of China,No.81900686Science and Technology Incubation Fund Project of Shaanxi Provincial People’s Hospital,No.2020YXM-08+2 种基金Technology Talent Support Program of Shaanxi Provincial People’s Hospital,No.2021BJ-07Key Projects of Shaanxi Provincial Department of Education,No.21JS038Medical Research Development Fund of Beijing Kangmeng Charity Foundation,No.7B202010.
文摘BACKGROUND Immature dendritic cells(imDCs)play an important role in the induction of donor-specific transplant immunotolerance.However,these cells have limitations,such as rapid maturation and a short lifespan in vivo.In previous studies,induced pluripotent stem cells(iPSCs)differentiated into imDCs,and sinomenine(SN)was used to inhibit the maturation of imDCs.AIM To study the capacity of SN to maintain iPSC-derived imDCs(SN-iPSCs-imDCs)in an immature state and the mechanism by which SN-iPSCs-imDCs induce immunotolerance.METHODS In this study,mouse iPSCs were induced to differentiate into imDCs in culture medium without or with SN(iPSCs-imDCs and SN-iPSCs-imDCs).The imDCrelated surface markers,endocytotic capacity of fluorescein isothiocyanate Dextran and apoptosis were analyzed by flow cytometry.The effects of iPSCs-imDCs and SNiPSCs-imDCs on T-cell stimulatory function,and regulatory T(Treg)cell proliferative function in vitro were analyzed by mixed lymphocyte reaction.Cytokine expression was detected by ELISA.The apoptosis-related proteins of iPSCs-DCs and SN-iPSCs-DCs were analyzed by western blotting.The induced immunotolerance of SN-iPSCs-DCs was evaluated by treating recipient Balb/c skin graft mice.Statistical evaluation of graft survival was performed using Kaplan–Meier curves.RESULTS Both iPSCs-imDCs and SN-iPSCs-imDCs were successfully obtained,and their biological characteristics and ability to induce immunotolerance were compared.SN-iPSCs-imDCs exhibited higher CD11c levels and lower CD80 and CD86 levels compared with iPSCs-imDCs.Reduced major histocompatibility complex II expression,worse T-cell stimulatory function,higher Treg cell proliferative function and stronger endocytotic capacity were observed with SN-iPSCs-imDCs(P<0.05).The levels of interleukin(IL)-2,IL-12,interferon-γin SN-iPSCs-imDCs were lower than those in iPSCs-imDCs,whereas IL-10 and transforming growth factor-βlevels were higher(P<0.05).The apoptosis rate of these cells was significantly higher(P<0.05),and the expression levels of cleaved caspase3,Bax and cleaved poly(ADP-ribose)polymerase were higher after treatment with lipopolysaccharides,but Bcl-2 was reduced.In Balb/c mice recipients immunized with iPSCsimDCs or SN-iPSCs-imDCs 7 d before skin grafting,the SN-iPSCs-imDCs group showed lower ability to inhibit donor-specific CD4+T-cell proliferation(P<0.05)and a higher capacity to induce CD4+CD25+FoxP3+Treg cell proliferation in the spleen(P<0.05).The survival span of C57bl/6 skin grafts was significantly prolonged in immunized Balb/c recipients with a donor-specific pattern.CONCLUSION This study demonstrated that SN-iPSCs-imDCs have potential applications in vitro and in vivo for induction of immunotolerance following organ transplantation.
基金The key program in science and technique of the National Ministry of Education (No.104169) and the major protocol in clinicalspecialty foundation of the National Ministry of Health (Year 2004-2006)
文摘Objective： To set up a method for isolation and culture of mature Sertoli cells and to estimate their effects on allogeneic islets cocultured in vitro. Methods： Adult SD rat testicular Sertoli cells were prepared successfully by three-step enzyme digestion. Then they were cocultured respectively with allogeneic islets and activated Wistar rat splenocytes. 24-hour cumulative insulin release and glucose-stimulated insulin secretion test were performed to detect islet function between pure islets culture group and coculture group. Splenocyte proliferation activity was determined by MTT colorimetry assay to observe the inhibition effect of Sertoli cells in different densities. Result： Firstly, in pure islet culture group, the 24-hour cumulative insulin release was gradually decreased in 21-day culture time. Compared to day 3, this change was significant on day 7 （P 〈 0.05） and on day 10,14,21 （P 〈 0.01）. In contrast, in coculture group, compared to day 3, the 24-hour cumulative insulin release was increased significantly on day 7 （P 〈 0.01 ）, and then gradually decreased on day 10 and 14, but still higher than that of day 3. It was on day 21 that it began to decrease compared to day 3 （P 〈 0.05）. During the culture time in vitro, the 24-hour cumulative insulin release of islet coculture group was significantly higher than that of pure islets culture group （P 〈 0.01）. In the case of stimulation index（SI）, there was a similar tendency as insulin release in the two groups. Secondly, mature Sertoli cells（1×10^6/mL） pretreated by 15 grays irradiation could decrease proliferation activity of activated splenocytes compared to that of control group （P 〈 0.01 ）. This inhibition effect was dose-dependent. Conclusion： Mature Sertoli cells can improve the function and prolong the survival of islet cells cultured in vitro. They can also provide an immune protection to islet cells. The approach described above might be applicable to human islet transplantation as soon as if it is also valid in large animal models.
基金This work was supported by the grants from the National Natural Science Foundation of China(Nos.81670681,81760137,81870514,81970668 and 81970670)the Fundamental Research Funds for the Central Universities(No.xjj2018091)+1 种基金the Clinical Research Award of the First Affiliated Hospital of Xi’an Jiaotong University(No.XJTU1AF-CRF-2019-008)the Special Supportive Program for Organ Transplantation by COTDF(No.2019JYJH04).
文摘Background:Delayed graft function(DGF)is the main cause of renal function failure after kidney transplantation.This study aims at investigating the value of hypothermic machine perfusion(HMP)parameters combined with perfusate biomarkers on predicting DGF and the time of renal function recovery after deceased donor(DD)kidney transplantation.Methods:HMP parameters,perfusate biomarkers and baseline characteristics of 113 DD kidney transplantations from January 1,2019 to August 31,2019 in the First Affiliated Hospital of Xi’an Jiaotong University were retrospectively analyzed using univariate and multivariate logistic regression analysis.Results:In this study,the DGF incidence was 17.7%(20/113);The multivariate logistic regression results showed that terminal resistance(OR:1.879,95%CI 1.145-3.56)and glutathione S-transferase(GST)(OR=1.62,95%CI 1.23-2.46)were risk factors for DGF;The Cox model analysis indicated that terminal resistance was an independent hazard factor for renal function recovery time(HR=0.823,95%CI 0.735-0.981).The model combining terminal resistance and GST(AUC=0.888,95%CI:0.842-0.933)significantly improved the DGF predictability compared with the use of terminal resistance(AUC=0.756,95%CI 0.693-0.818)or GST alone(AUC=0.729,95%CI 0.591-0.806).Conclusion:According to the factors analyzed in this study,the combination of HMP parameters and perfusate biomarkers displays a potent DGF predictive value.
基金grants from the Fundamental Research Funds for the Central Universities (No.xjj2018091)Major Clinical Research Projects of the First Affiliated Hospital of Xi'an Jiaotong University (No.XJTU1 AF-CRF-2015-005)+1 种基金Scientific and Technological Breakthrough in Social Development of Shaanxi Province (No.2016SF-246) National Natural Science Foundation of China (No.81670681 and 81760137).
文摘Background: Hypothermic machine perfusion(HMP) is being used more often in cardiac death kidney transplantation; however, the significance of assessing organ quality and predicting delayed graft function(DGF) by HMP parameters is still controversial. Therefore,we used a readily available HMP variable to design a scoring model that can identify the highest risk of DGF and provide the guidance and advice for organ allocation and DCD kidney assessment.Methods: From September 1, 2012 to August 31, 2016, 366 qualified kidneys were randomly assigned to the development and validation cohorts in a 2:1 distribution. The HMP variables of the development cohort served as candidate univariate predictors for DGF. The independent predictors of DGF were identified by multivariate logistic regression analysis with a P < 0.05. According to the odds ratios(ORs) value, each HMP variable was assigned a weighted integer, and the sum of the integers indicated the total risk score for each kidney. The validation cohort was used to verify the accuracy and reliability of the scoring model.Results: HMP duration(OR = 1.165, 95% confidence interval [CI ]: 1.008–1.360, P = 0.043), resistance(OR = 2.190, 95%CI: 1.032–10.20, P < 0.001), and flow rate(OR = 0.931, 95% CI: 0.894–0.967, P = 0.011) were the independent predictors of identified DGF. The HMP predictive score ranged from 0 to 14, and there was a clear increase in the incidence of DGF, from the low predictive score group to the very high predictive score group. We formed four increasingly serious risk categories(scores 0–3, 4–7, 8–11, and 12–14)according to the frequency associated with the different risk scores of DGF. The HMP predictive score indicates good discriminative power with a c?statistic of 0.706 in the validation cohort, and it had significantly better prediction value for DGF compared to both terminal flow(P = 0.012) and resistance(P = 0.006).Conclusion: The HMP predictive score is a good noninvasive tool for assessing the quality of DCD kidneys, and it is potentially useful for physicians in making optimal decisions about the organs donated.
基金supported by the National Natural Science Foundation of China(No.81470977,No.81970652)the Guangdong Basic and Applied Basic Research Foundation(No.2019A1515011219)the Science and Technology Planning Project of Guangzhou(No.201803010016).S.Z.is supported by the National Institutes of Health grants R01 AR059103,Star Award and R61 AR073409.
文摘Modulation of alloimmune responses is critical to improving transplant outcome and promoting long-term graft survival.To determine mechanisms by which a nonhematopoietic erythropoietin(EPO)derivative,carbamylated EPO(CEPO),regulates innate and adaptive immune cells and affects renal allograft survival,we utilized a rat model of fully MHC-mismatched kidney transplantation.CEPO administration markedly extended the survival time of kidney allografts compared with the transplant alone control group.This therapeutic effect was inhibited when the recipients were given LY294002,a selective inhibitor of the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway or anti-EPO receptor(EPOR)antibody,in addition to CEPO.In vitro,CEPO inhibited the differentiation and function of dendritic cells and modulated their production of proinflammatory and anti-inflammatory cytokines,along with activating the PI3K/AKT signaling pathway and increasing EPOR mRNA and protein expression by these innate immune cells.Moreover,after CD4^(+)T cells were exposed to CEPO the Th1/Th2 ratio decreased and the regulatory T cell(Treg)/Th17 ratio increased.These effects were abolished by LY294002 or anti-EPOR antibody,suggesting that CEPO regulates immune responses and promotes kidney allograft survival by activating the PI3K/AKT signaling pathway in an EPOR-dependent manner.The immunomodulatory and specific signaling pathway effects of CEPO identified in this study suggest a potential therapeutic approach to promoting kidney transplant survival.
