Objective： To investigate the effects of diltiazem and cyclosporine A （CsA） combination therapy on protecting the kidney, promoting graft functioning and improving post-transplanted kidney recovery. Methods： The b...Objective： To investigate the effects of diltiazem and cyclosporine A （CsA） combination therapy on protecting the kidney, promoting graft functioning and improving post-transplanted kidney recovery. Methods： The blood con- centrations of CsA, the condition of the post-transplant kidney, the rate of acute rejection （AR）, as well as hepatic and renal toxicity in 636 cases of renal transplant recipients were determined after being treated by CsA, with or without diltiazem. Results： Compared with the control group which received CsA, mycophenolate mofetil （MMF） and prednisolone （Pred） but lacked diltiazem, the group receiving these agents together with diltiazem required reduced dosage of CsA （P 〈 0.01）, while blood concentrations of CsA were significantly increased （P 〈 0.01）; the recovery time of graft function was reduced from （6.2± 1.5） d to （3.9± 1.4） d （P 〈 0.01）, and the rate of AR was decreased from 13.2% to 7.9% （P 〈 0.01）. Conclusion： In renal transplantation patients treated with CsA and diltiazem, blood concentrations of CsA were increased while the dosage was decreased. This efficient combination therapy reduced patients economic burden, at the same time retained kidney function, promoted graft function recovery and decreased hepatic and renal toxicity and the rate of AR.展开更多
The feasibility and the clinical value of the enzyme-multiplied immunoassay technique （EMIT） monitoring of blood concentrations of cyclosporine A （CsA） in patients treated with CsA were investigated after kidney t...The feasibility and the clinical value of the enzyme-multiplied immunoassay technique （EMIT） monitoring of blood concentrations of cyclosporine A （CsA） in patients treated with CsA were investigated after kidney transplantation. The validation method was performed to the EMIT determination of CsA blood concentration, the CsA whole blood trough concentrations （Co） of patients in different time periods after renal transplantation were monitored, and combined with the clinical complications, the statistical results were analyzed and compared. EMIT was precise, accurate and stable, also with a high quality control. The mean postoperative blood concentration of CsA was as follows： 〈1 month, （281.4± 57.9）ng/mL; 2 - 3 months, （264.5 ± 41.2） ng/mL; 4 - 5 months, （236.4 ± 38.9） ng/mL; 6 - 12 months, （206.5± 32.6）ng/mL; 〉12 months, （185.6± 28.1）ng/mL. The toxic reaction rate of CsA blood concentration within the recommended therapeutic concentration was 14.1%, significantly lower than that of the none-recommended dose group （37.2%） （P〈0.05）; the transplantation rejection rate was 4.4%, significantly lower than that of the none- recommended dose group （22.5%） （P〈0.05）. Using EMIT to monitor the blood concentration of CsA as the routine laboratory method is feasible, and is able to reduce the CsA toxicity and rejection significantly, leading to achieving the desired therapeutic effect.展开更多
In recent years, the use of new biomarkers in different phases of the diagnosis andtreatment of several diseases has allowed substantial improvement in clinicalpractice. The use of donor-derived cell-free DNA (dd-cfDN...In recent years, the use of new biomarkers in different phases of the diagnosis andtreatment of several diseases has allowed substantial improvement in clinicalpractice. The use of donor-derived cell-free DNA (dd-cfDNA) in organ transplantationhas led to significant progress in the treatment of post-transplantoutcomes, particularly after kidney transplantation. In addition, the use of ddcfDNAin organ transplantation has led to significant advancements in posttransplantoutcome monitoring. The aim of this study is to review many of therecent studies on the use of this biomarker and to evaluate its most relevantadvantages and limitations. dd-cfDNA is released from several types of cells ofthe transplanted organ, most often from endothelial cells and this happens in thecase of organ damage, most often rejection. Its presence in the bloodstream of therecipients is an important sign of graft damage;its principal advantage is in theavoidance of invasive tools such as renal biopsy. Additionally, several studiesreported that the finding of dd-cfDNA in the serum may precede histologicalabnormalities;its utility in the diagnosis of subclinical rejection is extremelyimportant. Among the principal limitations of this tool are the difficulty in distinguishingdifferent forms of graft damage. According to several studies this toolhas several limitations in diagnosing T-cell mediated rejection. In addition,particular care should be taken in distinguishing dd-cfDNA from recipientderivedcfDNA.展开更多
BACKGROUND Incisional hernia is one of the known complications of renal transplant surgery,with a reported incidence between 1.1%to 3.8%.Depending on the site and extent of incisional hernia,it may require surgery par...BACKGROUND Incisional hernia is one of the known complications of renal transplant surgery,with a reported incidence between 1.1%to 3.8%.Depending on the site and extent of incisional hernia,it may require surgery particularly if it contains the trans-planted kidney either partially or completely.The current common clinical prac-tice is to repair incisional hernias using polypropylene meshes,which have their own risks and benefits.Biological meshes,which are made from human or animal-derived connective tissue,are also in use and have a less inflammatory response.Recently,hybrid meshes have been developed.These are composed of both biological and synthetic products.One such example is OviTex 1S perma-nent,which is a sterile reinforced tissue matrix composed of ovine(sheep)derived extracellular matrix and monofilament polypropylene.In this case report,we are sharing our experience with the use of OviTex 1S in the repair of post-renal transplant incisional hernias.CASE SUMMARY We report four cases of post-renal transplant incisional hernia with a median time of 27 months post-surgery.The median size of the defect was 15 cm long.There was no post-operative complication.One patient required renal transplant biopsy after mesh repair,which was easily performed compared with polypropylene meshes repaired hernias in the past.CONCLUSION The OviTex 1S mesh provides benefits in hernial repairs pKTx,but cost is an issue,and their long-term viability is unclear.Continued use and reporting will help build a more informed picture.展开更多
Objective： To explore the effects of cytomegalovirus （CMV） infection on rejection-related gene expression in the endothelial cells of renal transplantation recipients. Methods： Endothelial cells （ECs） were cultu...Objective： To explore the effects of cytomegalovirus （CMV） infection on rejection-related gene expression in the endothelial cells of renal transplantation recipients. Methods： Endothelial cells （ECs） were cultured and stimulated by a variety of factors： A, normal control group; B, inactivated human cytomegalovirus （HCMV） infection group; C, HCMV infection group; D, HCMV supematant infection group; and E, ganciclovir HCMV group. Expression of intercellular adhesion molecule-1 （ICAM-1） and major histocompability complex （MHC） class I and class II antigens was detected by flow cytometry （FCM） and immuno- histochemistry. Results： We found characteristic CMV-infected ECs in this study. There were no significant differences among groups A, B and D （P〉0.05）. Although the expression levels of ICAM-1 were not significantly different between groups C and E （P〉0.05）, the ICAM-1 expression in these two groups was significantly higher than that in group A （P〈0.05）. ICAM-1 expression was detected in groups C and E, while there was no expression in groups A, B and D. Furthermore, there was no significant difference of ICAM-1 mRNA expression between groups C and E （P〉0.05）. Human leucocyte antigen （HLA）-ABC expression was detected in all the groups, while HLA-DR expression was only detected in groups C and E. There were no significant dif- ferences of HLA-ABC and HLA-DR expression among groups A, B and D （P〉0.05）. However, the HLA-ABC and HLA-DR expression levels in groups C and D were higher than those of the remaining groups previously reported （P〈0.05）. Meanwhile, the HLA-ABC and HLA-DR expression levels in group E were lower than those of group C （P〈0.05）. Conclusion： CMV could up-regulate the expression levels of ICAM-1 and MHC antigens, which was closely related to allograft rejection.展开更多
BACKGROUND Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection is a global pandemic that is associated with a high risk of morbidity and mortality among recipients of solid organ transplantation.In th...BACKGROUND Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection is a global pandemic that is associated with a high risk of morbidity and mortality among recipients of solid organ transplantation.In the course of acute SARS-CoV-2 infection,various laboratory markers have been identified as predictors for high risk of mortality.AIM To risk stratify renal transplant recipients(RTxR)using general demographic parameters,comorbidities and routine laboratory markers for the severity of the disease and its outcomes.We believe that learning about these routinely monitored parameters can help us plan better strategies for the RTxR follow-up program.METHODS This present study includes RTxR who acquired SARS-CoV-2 infection from March 2020 to February 2021.We recorded the basic demographics,comorbidities and routine laboratory markers.We investigated the impact of SARS-CoV-2 infection on RTxRs and risk-stratified the progression of disease severity and outcomes in terms of recovery or mortality.RESULTS From 505 RTxRs in our renal transplant follow-up program,29(7.75%)RTxRs had PCR-positive SARS-CoV-2 infection.We recorded 8 deaths from SARS-CoV-2 infection giving an overall mortality rate of 1.6%but a significant 27.6%mortality in SARS-CoV-2 positive recipients.Age more than 68 years,non-Caucasian ethnicity and male gender were associated with a significant drop in survival probability;P≤0.001.<0.001 and<0.0001 respectively.87.5%of the deceased were diabetic;P≤0.0.0001.Estimated glomerular filtration rate of less than 26 mL/min/1.73 m2,serum albumin less than 20 g/L,Hemoglobin less than 9.6 g/L and serum calcium less than 1.70 mmol/L were all associated with significantly increased risk of mortality;P=0.0128,<0.001,<0.0001 and 0.0061 respectively.CONCLUSION This study has identified some routinely used modifiable parameters in predicting a higher risk of mortality and morbidity.This knowledge can be used in RTxR follow-up programs by addressing these parameters early to help reduce the morbidity and mortality in RTxRs.展开更多
Objective To study the expression of B7-1 protein in biopsies in allograft renal transplantation,and explore the expression patern and the functional role of B7-1 molecule. Methods Renal allograft sample tissue by Tru...Objective To study the expression of B7-1 protein in biopsies in allograft renal transplantation,and explore the expression patern and the functional role of B7-1 molecule. Methods Renal allograft sample tissue by Tru-cut needle aspiration were taken from 64 paients(42 male,22 female) with renal transplantation, aging from 17 to 58 years old; 64 cases were categorized into six groups: ①acute rejection (AR n =22);②accelerated rejection (AAR n =8);③chronic rejection (CR n =10 );④hyperacute rejection (HR n =4);⑤allograft with stable function (ASF n =10); ⑥health donor kidney (HDK n =10);Immunohistochemical assays(ABC) were used, and comparison B7-1 and HLA-DR expression between tubularand interstitial,the number of interstitial infiltrating lymphocytes. Results ①The sequence of the expression of B7-1 molecule in terms of intensity from the strongest to the weakest in different groups is AR group, AAR group, CR group, HR group,ASF group and HDK group; ②During acute rejection response, a large number of CD4 and CD8 T lymphocytes infiltrate kidney interstitium, accompanied by strong expression of HLA-DR in tubular cell(donor MHC-Ⅱantigen),which is the first signal necessary for T lymphocyte activation. Conclusion The results demonstrate that B7-1 expression of tubular cells as APC actively take part in immunological reactions and play an important role in expanding the immunological reactions.展开更多
BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal tract.As most of them harbor a KIT mutation(75%),selective kinase inhibitors are the therapeutic option a...BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal tract.As most of them harbor a KIT mutation(75%),selective kinase inhibitors are the therapeutic option and show a sustained objective response among patients with metastatic or unresectable GISTs.A wellknown higher risk of neoplasm has been described among renal transplant recipients(RTRs).Nevertheless,only few cases of GIST onset among transplant patients have been reported in the literature.CASE SUMMARY Here,we describe 2 cases of gastric GIST occurring during the follow-up of RTRs.We also review the existing literature concerning GIST occurrence in transplant patients.In total and in association with our 2 cases,16 patients have been reported.The median age was 59.5 years and 69%were male.With a median tumor size of 45 mm,no patient displayed metastatic dissemination at diagnosis.Time from transplantation to diagnosis was highly variable between 5 mo and 21 years.Histopathological data mostly revealed high risk of progression(43%).Death increased to 29%during follow-up.Surgical treatment was systematically performed when the tumor was operable(94%).The use of adjuvant therapy was uncommon(19%).CONCLUSION GISTs represent rare but potentially severe malignant complication among transplant patients.展开更多
Objective: To use bioinformatics technology to analyse differentially expressed genes in chronic rejection after renal transplantation, we can screen out potential pathogenic targets associated with the development of...Objective: To use bioinformatics technology to analyse differentially expressed genes in chronic rejection after renal transplantation, we can screen out potential pathogenic targets associated with the development of this disease, providing a theoretical basis for finding new therapeutic targets. Methods: Gene microarray data were downloaded from the Gene Expression Profiling Integrated Database (GEO) and cross-calculated to identify differentially expressed genes (DEGs). Analysis of differentially expressed genes (DEGs) with gene ontology (GO) is a method used to study the differences in gene expression under different conditions as well as their functions and interrelationships, while Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis is a tool used to explore the functions and pathways of genes in specific biological processes. By calculating the distribution of immune cell infiltration, the result of immune infiltration in the rejection group can be analysed as a trait in Weighted Gene Co-Expression Network Analysis (WGCNA) for genes associated with rejection. Then, protein-protein interaction networks (PPI) were constructed using the STRING database and Cytoscape software to identify hub gene markers. Results: A total of 60 integrated DEGs were obtained from 3 datasets (GSE7392, GSE181757, GSE222889). By GO and KEGG analysis, the GEDs were mainly concentrated in the regulation of immune response, defence response, regulation of immune system processes, and stimulation response. The pathways were mainly enriched in antigen processing and presentation, EBV infection, graft-versus-host, allograft rejection, and natural killer cell-mediated cytotoxicity. After further screening using WGCNA and PPI networks, HLA-A, HLA-B, HLA-F, and TYROBP were identified as hub genes (Hub genes). The data GSE21374 with clinical information was selected to construct the diagnostic efficacy and risk prediction model plots of the four hub genes, and the results concluded that all four Hub genes had good diagnostic value (area under the curve in the range of 0.794-0.819). From the inference, it can be concluded that the four genes, HLA-A, HLA-B, HLA-F and TYROBP, may have an important role in the development and progression of chronic rejection after renal transplantation. Conclusion: DEGs play an important role in the study of the pathogenesis of chronic rejection after renal transplantation, and can provide theoretical support for further research on the pathogenesis of chronic rejection after renal transplantation and the discovery of new therapeutic targets through enrichment analysis and pivotal gene screening, as well as inferential analyses of related diagnostic efficacy and disease risk prediction.展开更多
Congratulations to the publisher,members of the editorial board of the journal,all the authors and readers for launching the World Journal of Transplantation(WJT)as a new member of the World series journal family.Tran...Congratulations to the publisher,members of the editorial board of the journal,all the authors and readers for launching the World Journal of Transplantation(WJT)as a new member of the World series journal family.Transplantations are rapidly evolving and share knowledge with a number of basic and clinical sciences:molecular biology,stem cell investigators,immune system,pharmacology,biotechnology,surgery and physicians of different organs such as the kidneys,liver,heart,lung,bone marrow and so on.The WJT is a peer reviewed open access journal centered on the different fields involved in transplant activity.If you want to share your experiences and new findings in the field of transplantation with your peers you will find the WJT a good media to publish your papers.展开更多
Mycophenolic acid(MPA),the active moiety of both mycophenolate mofetil(MMF)and enteric-coated mycophenolate sodium(EC-MPS),serves as a primary immunosuppressant for maintaining solid organ transplants.Therapeutic drug...Mycophenolic acid(MPA),the active moiety of both mycophenolate mofetil(MMF)and enteric-coated mycophenolate sodium(EC-MPS),serves as a primary immunosuppressant for maintaining solid organ transplants.Therapeutic drug monitoring(TDM)enhances treatment outcomes through tailored approaches.This study aimed to develop an evidence-based guideline for MPA TDM,facilitating its rational application in clinical settings.The guideline plan was drawn from the Institute of Medicine and World Health Organization(WHO)guidelines.Using the Delphi method,clinical questions and outcome indicators were generated.Systematic reviews,Grading of Recommendations Assessment,Development,and Evaluation(GRADE)evidence quality evaluations,expert opinions,and patient values guided evidence-based suggestions for the guideline.External reviews further refined the recommendations.The guideline for the TDM of MPA(IPGRP-2020CN099)consists of four sections and 16 recommendations encompassing target populations,monitoring strategies,dosage regimens,and influencing factors.High-risk populations,timing of TDM,area under the curve(AUC)versus trough concentration(C0),target concentration ranges,monitoring frequency,and analytical methods are addressed.Formulation-specific recommendations,initial dosage regimens,populations with unique considerations,pharmacokinetic-informed dosing,body weight factors,pharmacogenetics,and drug–drug interactions are covered.The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy,promoting standardization of MPA TDM,and enhancing treatment efficacy and safety.展开更多
BACKGROUND Living donor kidney transplantation is the optimal method of long-term renal replacement therapy.Minimally invasive donor nephrectomy techniques,such as robot-assisted(RALDN)and hand-assisted(HALDN)laparosc...BACKGROUND Living donor kidney transplantation is the optimal method of long-term renal replacement therapy.Minimally invasive donor nephrectomy techniques,such as robot-assisted(RALDN)and hand-assisted(HALDN)laparoscopic procedures,are well-established in high-income countries and are being increasingly adopted worldwide.Nevertheless,no studies have reported surgical outcomes of RALDN donor nephrectomy from a United Kingdom center to date.AIM To compare surgical outcomes between RALDN and HALDN laparoscopic donor nephrectomy in a United Kingdom high-volume living kidney donor transplant program.METHODS A case-control matching analysis was performed based on the following parameters:Sex,age,body mass index,procedure laterality,number of renal arteries,and previous abdominal surgeries.Key surgical outcomes,including primary warm ischemia time,operative duration,and post-operative recovery,were evaluated.RESULTS In this cohort of 140 living donors(70 RALDN vs 70 HALDN),donor and recipient outcomes were equivalent across key metrics:Pain scores,overall complication rates,readmissions,reoperations,and creatinine levels at 30 days and 1 year.Recipient long-term renal function did not differ between groups.Operative time for RALDN decreased significantly over the study period,indicating progressive improvement along the learning curve.Although RALDN was associated with a modestly longer mean warm ischaemia time(3.53 minutes vs 2.76 minutes,P<0.001)and extended hospital stay(4.21 days vs 3.17 days,P<0.001),these did not translate into any disadvantage in clinical outcomes.CONCLUSION In this first United Kingdom comparative cohort,RALDN demonstrated excellent safety and efficacy,even in the early phase of our programme,matching the outcomes of the well-established,gold-standard HALDN approach.Moreover,the pronounced learning-curve trajectory suggests considerable potential for further improvements in robotic surgical outcomes as the programme matures.展开更多
Ischemia/reperfusion injury is an unavoidable relevant consequence after kidney transplantation and influences short term as well as long-term graft outcome. Clinically ischemia/reperfusion injury is associated with d...Ischemia/reperfusion injury is an unavoidable relevant consequence after kidney transplantation and influences short term as well as long-term graft outcome. Clinically ischemia/reperfusion injury is associated with delayed graft function, graft rejection, chronic rejection and chronic graft dysfunction. Ischemia/reperfusion affects many regulatory systems at the cellular level as well as in the renal tissue that result in a distinct inflammatory reaction of the kidney graft. Underlying factors of ischemia reperfusion include energy metabolism, cellular changes of the mitochondria and cellular membranes, initiation of different forms of cell death-like apoptosis and necrosis together with a recently discovered mixed form termed necroptosis. Chemokines and cytokines together with other factors promote the inflammatory response leading to activation of the innate immune system as well as the adaptive immune system. If the inflammatory reaction continues within the graft tissue, a progressive interstitial fibrosis develops that impacts long-term graft outcome. It is of particular importance in kidney transplantation to understand the underlying mechanisms and effects of ischemia/reperfusion on the graft as this knowledge also opens strategies to prevent or treat ischemia/reperfusion injury after transplantation in order to improve graft outcome.展开更多
AIM. To investigate the influence of heme oxygenase-1 （HO-1） gene transfer on the viability and function of cultured rat islets in vitro. METHODS： Islets were isolated from the pancreata of Sprague-Dawley rats by i...AIM. To investigate the influence of heme oxygenase-1 （HO-1） gene transfer on the viability and function of cultured rat islets in vitro. METHODS： Islets were isolated from the pancreata of Sprague-Dawley rats by intraductal collagenase digestion, and purified by discontinuous Ficoll density gradient centrifugation. Purified rat islets were transfected with adenoviral vectors containing human HO-1 gene （Ad- HO-1） or enhanced green fluorescent protein gene （Ad- EGFP）, and then cultured for seven days. Transfection was confirmed by fluorescence microscopy and Western blot. Islet viability was evaluated by acridine orange/ propidium iodide fluorescent staining. Glucose-stimulated insulin release was detected using insulin radioimmunoassay kits and was used to assess the function of islets. Stimulation index （SI） was calculated by dividing the insulin release upon high glucose stimulation by the insulin release upon low glucose stimulation. RESULTS： After seven days culture, the viability of cultured rat islets decreased significantly （92% ± 6% vs 52% ± 13%, P 〈 0.05）, and glucose-stimulated insulin release also decreased significantly （6.47 ± 0.55 mIU/ L/30IEO vs 4.57 ± 0.40 mIU/L/3OIEO., 14.93 ± 1.17 mIU/L/30IEQ vs 9.63 ± 0.71 mIU/L/30IEQ, P 〈 0.05）. Transfection of rat islets with adenoviral vectors at an 1±10 of 20 was efficient, and did not impair islet function. At 7 d post-transfection, the viability of Ad-HO-1 transfected islets was higher than that of control islets（71% ± 15% vs 52% ± 13%, P 〈 0.05）. There was no significant difference in insulin release upon low glucose stimulation （2.8 mmol/L） among Ad-HO-1 transfected group, Ad-EGFP transfected group, and control group （P 〉 0.05）, while when stimulated by high glucose （16.7 mmol/L） solution, insulin release in Ad-HO-1 transfected group was significantly higher than that in Ad-EGFP transfected group and control group, respectively （12.50 ±2.17 mIU/L/30IEQ vs 8.87 ± 0.65 mIU/L/30IEQ, 12.50 ± 2.17 mIU/L/30IEQ vs 9.63 ± 0.71 mIU/L/30IEQ, P 〈 0.05）. The SI of Ad-HO-1 transfected group was also significantly higher than that of Ad-EGFP transfected group and control group, respectively （2.21 ± 0.02 vs 2.08 ± 0.05; 2.21 ± 0.02 vs 2.11 ± 0.03, P 〈 0.05）. CONCLUSION： The viability and function of rat islets decrease over time in in vitro culture, and heine oxygenase-1 gene transfer could improve the viability and function of cultured rat islets.展开更多
Objective: In this paper we compared the two methods of cell sorting (magnetic cell sorting and flow cytometry sorting) for the isolation and function analysis of mouse CD4+ CD25+ regulatory T (Treg) cells, in order t...Objective: In this paper we compared the two methods of cell sorting (magnetic cell sorting and flow cytometry sorting) for the isolation and function analysis of mouse CD4+ CD25+ regulatory T (Treg) cells, in order to inform further studies in Treg cell function. Methods: We separately used magnetic cell sorting and flow cytometry sorting to identify CD4+ CD25+ Treg cells. After magnetic cell separation, we further used flow cytometry to analyze the purity of CD4+ CD25+ Treg cells, trypan blue staining to detect cell viability, and propidium iodide (PI) staining to assess the cell viability. We detected the immune inhibition of CD4+ CD25+ Treg cells in the in vitro proliferation experiments. Results: The results showed that compared to flow cytometry sorting, magnetic cell sorting took more time and effort, but fewer live cells were obtained than with flow cytometry sorting. The CD4+ CD25+ Treg cells, however, obtained with both methods have similar immunosuppressive capacities. Conclusion: The result suggests that both methods can be used in isolating CD4+ CD25+ Treg cells, and one can select the best method according to specific needs and availability of the methodologies.展开更多
Allo-antibodies, particularly when donor specific, are one of the most important factors that cause both early and late graft dysfunction. The authors review the current state of the art concerning this important issu...Allo-antibodies, particularly when donor specific, are one of the most important factors that cause both early and late graft dysfunction. The authors review the current state of the art concerning this important issue in renal transplantation. Many antibodies have been recognized as mediators of renal injury. In particular donorspecific-Human Leukocyte Antigens antibodies appear to play a major role. New techniques, such as solid phase techniques and Luminex, have revealed these antibodies from patient sera. Other new techniques have uncovered alloantibodies and signs of complement activation in renal biopsy specimens. It has been acknowledged that the old concept of chronic renal injury caused by calcineurine inhibitors toxicity should be replaced in many cases by alloantibodies acting against the graft. In addition, the number of patients on waiting lists with preformed anti-human leukocyte antigens(HLA) antibodies is increasing, primarily from patients with a history of renal transplant failure already been sensitized. We should distinguish early and late acute antibody-mediated rejection from chronic antibody-mediated rejection. The latter often manifets late during the course of the posttransplant period and may be difficult to recognize if specific techniques are not applied. Different therapeutic strategies are used to control antibody-induced damage.These strategies may be applied prior to transplantation or, in the case of acute antibody-mediated rejection, after transplantation. Many new drugs are appearing at the horizon; however, these drugs are far from the clinic because they are in phase Ⅰ-Ⅱ of clinical trials. Thus the pipeline for the near future appears almost empty.展开更多
Synthetic cannabinoids have become a common drug of abuse in recent years and their toxicities have come to light as well. They are known to be notorious for the kidneys, with acute tubular necrosis, acute interstitia...Synthetic cannabinoids have become a common drug of abuse in recent years and their toxicities have come to light as well. They are known to be notorious for the kidneys, with acute tubular necrosis, acute interstitial nephritis and rhabdomyolysis induced renal injury being the frequent nephrotoxic outcomes in users. We report a case of bilateral renal cortical necrosis, leading to irreversible renal damage and lifelong dialysis dependency.展开更多
This review revises the reclassification of the mem-branoproliferative glomerulonephritis （MPGN） after the consensus conference that by 2015 reclassified all the glomerulonephritis basing on etiology and patho-genes...This review revises the reclassification of the mem-branoproliferative glomerulonephritis （MPGN） after the consensus conference that by 2015 reclassified all the glomerulonephritis basing on etiology and patho-genesis, instead of the histomorphological aspects. After reclassification, two types of MPGN are to date recognized： The immunocomplexes mediated MPGN and the complement mediated MPGN. The latter type is more extensively described in the review either because several of these entities are completely new or because the improved knowledge of the complement cascade allowed for new diagnostic and therapeutic approaches. Overall the complement mediated MPGN are related to acquired or genetic cause. The presence of circulating auto antibodies is the principal acquired cause. Genetic wide association studies and family studies allowed to recognize genetic mutations of different types as causes of the complement dysregulation. The complement cascade is a complex phenomenon and activating factors and regulating factors should be distinguished. Genetic mutations causing abnormalities either in activating or in regulating factors have been described. The diagnosis of the complement mediated MPGN requires a complete study of all these different complement factors. As a consequence, new therapeutic approaches are becoming available. Indeed, in addition to a nonspecifc treatment and to the immunosuppression that has the aim to block the auto antibodies production, the specific inhibition of complement activation is relatively new and may act either blocking the C5 convertase or the C3 convertase. The drugs acting on C3 convertase are still in different phases of clinical development and might represent drugs for the future. Overall the authors consider that one of the principal problems in fnding new types of drugs are both the rarity of the disease and the consequent poor interest in the marketing and the lack of large international cooperative studies.展开更多
The recurrence of renal disease after renal transplantation is becoming one of the main causes of graft loss afterkidney transplantation. This principally concerns some of the original diseases as the atypical hemolyt...The recurrence of renal disease after renal transplantation is becoming one of the main causes of graft loss afterkidney transplantation. This principally concerns some of the original diseases as the atypical hemolytic uremic syndrome(HUS), the membranoproliferative glomerulonephritis(MPGN), in particular the MPGN now called C3 glomerulopathy. Both this groups of renal diseases are characterized by congenital(genetic) or acquired(autoantibodies) modifications of the alternative pathway of complement. These abnormalities often remain after transplantation because they are constitutional and poorly influenced by the immunosuppression. This fact justifies the high recurrence rate of these diseases. Early diagnosis of recurrence is essential for an optimal therapeutically approach, whenever possible. Patients affected by end stage renal disease due to C3 glomerulopathies or to atypical HUS, may be transplanted with extreme caution. Living donor donation from relatives is not recommended because members of the same family may be affected by the same gene mutation. Different therapeutically approaches have been attempted either for recurrence prevention and treatment. The most promising approach is represented by complement inhibitors. Eculizumab, a monoclonal antibody against C5 convertase is the most promising drug, even if to date is not known how long the therapy should be continued and which are the best dosing. These facts face the high costs of the treatment. Eculizumab resistant patients have been described. They could benefit by a C3 convertase inhibitor, but this class of drugs is by now the object of randomized controlled trials.展开更多
基金supported by the"13115"Innovation Technology Project of Special Purpose of Shaanxi Province(No.2087ZDKG-67)the National Natural Science Foundation of China(No.30772096)+2 种基金the Natural Science Foundation of Shaanxi Province(No.2007C2C12)the Project of the National Science Foundation for Distinguished Young Scholars of First Affiliated Hospital of the Medical College of Xi'an Jiaotong University(No.2006YK4)the Science Research of Sha-anxi Health Department(No.08D25)
文摘Objective： To investigate the effects of diltiazem and cyclosporine A （CsA） combination therapy on protecting the kidney, promoting graft functioning and improving post-transplanted kidney recovery. Methods： The blood con- centrations of CsA, the condition of the post-transplant kidney, the rate of acute rejection （AR）, as well as hepatic and renal toxicity in 636 cases of renal transplant recipients were determined after being treated by CsA, with or without diltiazem. Results： Compared with the control group which received CsA, mycophenolate mofetil （MMF） and prednisolone （Pred） but lacked diltiazem, the group receiving these agents together with diltiazem required reduced dosage of CsA （P 〈 0.01）, while blood concentrations of CsA were significantly increased （P 〈 0.01）; the recovery time of graft function was reduced from （6.2± 1.5） d to （3.9± 1.4） d （P 〈 0.01）, and the rate of AR was decreased from 13.2% to 7.9% （P 〈 0.01）. Conclusion： In renal transplantation patients treated with CsA and diltiazem, blood concentrations of CsA were increased while the dosage was decreased. This efficient combination therapy reduced patients economic burden, at the same time retained kidney function, promoted graft function recovery and decreased hepatic and renal toxicity and the rate of AR.
基金supported by the Project 973 Monitoring of the Immune Status and Rejection After Organ Transplantation"(2009CB522400)the National Natural Science Foundation of China(No.30972947)
文摘The feasibility and the clinical value of the enzyme-multiplied immunoassay technique （EMIT） monitoring of blood concentrations of cyclosporine A （CsA） in patients treated with CsA were investigated after kidney transplantation. The validation method was performed to the EMIT determination of CsA blood concentration, the CsA whole blood trough concentrations （Co） of patients in different time periods after renal transplantation were monitored, and combined with the clinical complications, the statistical results were analyzed and compared. EMIT was precise, accurate and stable, also with a high quality control. The mean postoperative blood concentration of CsA was as follows： 〈1 month, （281.4± 57.9）ng/mL; 2 - 3 months, （264.5 ± 41.2） ng/mL; 4 - 5 months, （236.4 ± 38.9） ng/mL; 6 - 12 months, （206.5± 32.6）ng/mL; 〉12 months, （185.6± 28.1）ng/mL. The toxic reaction rate of CsA blood concentration within the recommended therapeutic concentration was 14.1%, significantly lower than that of the none-recommended dose group （37.2%） （P〈0.05）; the transplantation rejection rate was 4.4%, significantly lower than that of the none- recommended dose group （22.5%） （P〈0.05）. Using EMIT to monitor the blood concentration of CsA as the routine laboratory method is feasible, and is able to reduce the CsA toxicity and rejection significantly, leading to achieving the desired therapeutic effect.
文摘In recent years, the use of new biomarkers in different phases of the diagnosis andtreatment of several diseases has allowed substantial improvement in clinicalpractice. The use of donor-derived cell-free DNA (dd-cfDNA) in organ transplantationhas led to significant progress in the treatment of post-transplantoutcomes, particularly after kidney transplantation. In addition, the use of ddcfDNAin organ transplantation has led to significant advancements in posttransplantoutcome monitoring. The aim of this study is to review many of therecent studies on the use of this biomarker and to evaluate its most relevantadvantages and limitations. dd-cfDNA is released from several types of cells ofthe transplanted organ, most often from endothelial cells and this happens in thecase of organ damage, most often rejection. Its presence in the bloodstream of therecipients is an important sign of graft damage;its principal advantage is in theavoidance of invasive tools such as renal biopsy. Additionally, several studiesreported that the finding of dd-cfDNA in the serum may precede histologicalabnormalities;its utility in the diagnosis of subclinical rejection is extremelyimportant. Among the principal limitations of this tool are the difficulty in distinguishingdifferent forms of graft damage. According to several studies this toolhas several limitations in diagnosing T-cell mediated rejection. In addition,particular care should be taken in distinguishing dd-cfDNA from recipientderivedcfDNA.
文摘BACKGROUND Incisional hernia is one of the known complications of renal transplant surgery,with a reported incidence between 1.1%to 3.8%.Depending on the site and extent of incisional hernia,it may require surgery particularly if it contains the trans-planted kidney either partially or completely.The current common clinical prac-tice is to repair incisional hernias using polypropylene meshes,which have their own risks and benefits.Biological meshes,which are made from human or animal-derived connective tissue,are also in use and have a less inflammatory response.Recently,hybrid meshes have been developed.These are composed of both biological and synthetic products.One such example is OviTex 1S perma-nent,which is a sterile reinforced tissue matrix composed of ovine(sheep)derived extracellular matrix and monofilament polypropylene.In this case report,we are sharing our experience with the use of OviTex 1S in the repair of post-renal transplant incisional hernias.CASE SUMMARY We report four cases of post-renal transplant incisional hernia with a median time of 27 months post-surgery.The median size of the defect was 15 cm long.There was no post-operative complication.One patient required renal transplant biopsy after mesh repair,which was easily performed compared with polypropylene meshes repaired hernias in the past.CONCLUSION The OviTex 1S mesh provides benefits in hernial repairs pKTx,but cost is an issue,and their long-term viability is unclear.Continued use and reporting will help build a more informed picture.
基金Project supported by the National Natural Science Foundation of China (No. 30772096)the Clinical Key Disciplines of National Public Health Department, the Major Scientific and Technological Special Projects of Shannxi Province (No. 2007ZDKG-67)the Natural Science Foundation of Shaanxi Province (No. 30571799), China
文摘Objective： To explore the effects of cytomegalovirus （CMV） infection on rejection-related gene expression in the endothelial cells of renal transplantation recipients. Methods： Endothelial cells （ECs） were cultured and stimulated by a variety of factors： A, normal control group; B, inactivated human cytomegalovirus （HCMV） infection group; C, HCMV infection group; D, HCMV supematant infection group; and E, ganciclovir HCMV group. Expression of intercellular adhesion molecule-1 （ICAM-1） and major histocompability complex （MHC） class I and class II antigens was detected by flow cytometry （FCM） and immuno- histochemistry. Results： We found characteristic CMV-infected ECs in this study. There were no significant differences among groups A, B and D （P〉0.05）. Although the expression levels of ICAM-1 were not significantly different between groups C and E （P〉0.05）, the ICAM-1 expression in these two groups was significantly higher than that in group A （P〈0.05）. ICAM-1 expression was detected in groups C and E, while there was no expression in groups A, B and D. Furthermore, there was no significant difference of ICAM-1 mRNA expression between groups C and E （P〉0.05）. Human leucocyte antigen （HLA）-ABC expression was detected in all the groups, while HLA-DR expression was only detected in groups C and E. There were no significant dif- ferences of HLA-ABC and HLA-DR expression among groups A, B and D （P〉0.05）. However, the HLA-ABC and HLA-DR expression levels in groups C and D were higher than those of the remaining groups previously reported （P〈0.05）. Meanwhile, the HLA-ABC and HLA-DR expression levels in group E were lower than those of group C （P〈0.05）. Conclusion： CMV could up-regulate the expression levels of ICAM-1 and MHC antigens, which was closely related to allograft rejection.
基金Compliance with local ethical and data protection policies.Registered with St Georges University Hospitals NHS Foundation Trust Quality Assurance Department.Registration no AUD1000854。
文摘BACKGROUND Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection is a global pandemic that is associated with a high risk of morbidity and mortality among recipients of solid organ transplantation.In the course of acute SARS-CoV-2 infection,various laboratory markers have been identified as predictors for high risk of mortality.AIM To risk stratify renal transplant recipients(RTxR)using general demographic parameters,comorbidities and routine laboratory markers for the severity of the disease and its outcomes.We believe that learning about these routinely monitored parameters can help us plan better strategies for the RTxR follow-up program.METHODS This present study includes RTxR who acquired SARS-CoV-2 infection from March 2020 to February 2021.We recorded the basic demographics,comorbidities and routine laboratory markers.We investigated the impact of SARS-CoV-2 infection on RTxRs and risk-stratified the progression of disease severity and outcomes in terms of recovery or mortality.RESULTS From 505 RTxRs in our renal transplant follow-up program,29(7.75%)RTxRs had PCR-positive SARS-CoV-2 infection.We recorded 8 deaths from SARS-CoV-2 infection giving an overall mortality rate of 1.6%but a significant 27.6%mortality in SARS-CoV-2 positive recipients.Age more than 68 years,non-Caucasian ethnicity and male gender were associated with a significant drop in survival probability;P≤0.001.<0.001 and<0.0001 respectively.87.5%of the deceased were diabetic;P≤0.0.0001.Estimated glomerular filtration rate of less than 26 mL/min/1.73 m2,serum albumin less than 20 g/L,Hemoglobin less than 9.6 g/L and serum calcium less than 1.70 mmol/L were all associated with significantly increased risk of mortality;P=0.0128,<0.001,<0.0001 and 0.0061 respectively.CONCLUSION This study has identified some routinely used modifiable parameters in predicting a higher risk of mortality and morbidity.This knowledge can be used in RTxR follow-up programs by addressing these parameters early to help reduce the morbidity and mortality in RTxRs.
文摘Objective To study the expression of B7-1 protein in biopsies in allograft renal transplantation,and explore the expression patern and the functional role of B7-1 molecule. Methods Renal allograft sample tissue by Tru-cut needle aspiration were taken from 64 paients(42 male,22 female) with renal transplantation, aging from 17 to 58 years old; 64 cases were categorized into six groups: ①acute rejection (AR n =22);②accelerated rejection (AAR n =8);③chronic rejection (CR n =10 );④hyperacute rejection (HR n =4);⑤allograft with stable function (ASF n =10); ⑥health donor kidney (HDK n =10);Immunohistochemical assays(ABC) were used, and comparison B7-1 and HLA-DR expression between tubularand interstitial,the number of interstitial infiltrating lymphocytes. Results ①The sequence of the expression of B7-1 molecule in terms of intensity from the strongest to the weakest in different groups is AR group, AAR group, CR group, HR group,ASF group and HDK group; ②During acute rejection response, a large number of CD4 and CD8 T lymphocytes infiltrate kidney interstitium, accompanied by strong expression of HLA-DR in tubular cell(donor MHC-Ⅱantigen),which is the first signal necessary for T lymphocyte activation. Conclusion The results demonstrate that B7-1 expression of tubular cells as APC actively take part in immunological reactions and play an important role in expanding the immunological reactions.
文摘BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal tract.As most of them harbor a KIT mutation(75%),selective kinase inhibitors are the therapeutic option and show a sustained objective response among patients with metastatic or unresectable GISTs.A wellknown higher risk of neoplasm has been described among renal transplant recipients(RTRs).Nevertheless,only few cases of GIST onset among transplant patients have been reported in the literature.CASE SUMMARY Here,we describe 2 cases of gastric GIST occurring during the follow-up of RTRs.We also review the existing literature concerning GIST occurrence in transplant patients.In total and in association with our 2 cases,16 patients have been reported.The median age was 59.5 years and 69%were male.With a median tumor size of 45 mm,no patient displayed metastatic dissemination at diagnosis.Time from transplantation to diagnosis was highly variable between 5 mo and 21 years.Histopathological data mostly revealed high risk of progression(43%).Death increased to 29%during follow-up.Surgical treatment was systematically performed when the tumor was operable(94%).The use of adjuvant therapy was uncommon(19%).CONCLUSION GISTs represent rare but potentially severe malignant complication among transplant patients.
基金National Natural Science Foundation of China(No.82260154)。
文摘Objective: To use bioinformatics technology to analyse differentially expressed genes in chronic rejection after renal transplantation, we can screen out potential pathogenic targets associated with the development of this disease, providing a theoretical basis for finding new therapeutic targets. Methods: Gene microarray data were downloaded from the Gene Expression Profiling Integrated Database (GEO) and cross-calculated to identify differentially expressed genes (DEGs). Analysis of differentially expressed genes (DEGs) with gene ontology (GO) is a method used to study the differences in gene expression under different conditions as well as their functions and interrelationships, while Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis is a tool used to explore the functions and pathways of genes in specific biological processes. By calculating the distribution of immune cell infiltration, the result of immune infiltration in the rejection group can be analysed as a trait in Weighted Gene Co-Expression Network Analysis (WGCNA) for genes associated with rejection. Then, protein-protein interaction networks (PPI) were constructed using the STRING database and Cytoscape software to identify hub gene markers. Results: A total of 60 integrated DEGs were obtained from 3 datasets (GSE7392, GSE181757, GSE222889). By GO and KEGG analysis, the GEDs were mainly concentrated in the regulation of immune response, defence response, regulation of immune system processes, and stimulation response. The pathways were mainly enriched in antigen processing and presentation, EBV infection, graft-versus-host, allograft rejection, and natural killer cell-mediated cytotoxicity. After further screening using WGCNA and PPI networks, HLA-A, HLA-B, HLA-F, and TYROBP were identified as hub genes (Hub genes). The data GSE21374 with clinical information was selected to construct the diagnostic efficacy and risk prediction model plots of the four hub genes, and the results concluded that all four Hub genes had good diagnostic value (area under the curve in the range of 0.794-0.819). From the inference, it can be concluded that the four genes, HLA-A, HLA-B, HLA-F and TYROBP, may have an important role in the development and progression of chronic rejection after renal transplantation. Conclusion: DEGs play an important role in the study of the pathogenesis of chronic rejection after renal transplantation, and can provide theoretical support for further research on the pathogenesis of chronic rejection after renal transplantation and the discovery of new therapeutic targets through enrichment analysis and pivotal gene screening, as well as inferential analyses of related diagnostic efficacy and disease risk prediction.
文摘Congratulations to the publisher,members of the editorial board of the journal,all the authors and readers for launching the World Journal of Transplantation(WJT)as a new member of the World series journal family.Transplantations are rapidly evolving and share knowledge with a number of basic and clinical sciences:molecular biology,stem cell investigators,immune system,pharmacology,biotechnology,surgery and physicians of different organs such as the kidneys,liver,heart,lung,bone marrow and so on.The WJT is a peer reviewed open access journal centered on the different fields involved in transplant activity.If you want to share your experiences and new findings in the field of transplantation with your peers you will find the WJT a good media to publish your papers.
基金supported by the National Natural Science Foundation of China(NSFC)(No.72304007)the Huatong Guokang Medical Research Fund(No.2023HT010)。
文摘Mycophenolic acid(MPA),the active moiety of both mycophenolate mofetil(MMF)and enteric-coated mycophenolate sodium(EC-MPS),serves as a primary immunosuppressant for maintaining solid organ transplants.Therapeutic drug monitoring(TDM)enhances treatment outcomes through tailored approaches.This study aimed to develop an evidence-based guideline for MPA TDM,facilitating its rational application in clinical settings.The guideline plan was drawn from the Institute of Medicine and World Health Organization(WHO)guidelines.Using the Delphi method,clinical questions and outcome indicators were generated.Systematic reviews,Grading of Recommendations Assessment,Development,and Evaluation(GRADE)evidence quality evaluations,expert opinions,and patient values guided evidence-based suggestions for the guideline.External reviews further refined the recommendations.The guideline for the TDM of MPA(IPGRP-2020CN099)consists of four sections and 16 recommendations encompassing target populations,monitoring strategies,dosage regimens,and influencing factors.High-risk populations,timing of TDM,area under the curve(AUC)versus trough concentration(C0),target concentration ranges,monitoring frequency,and analytical methods are addressed.Formulation-specific recommendations,initial dosage regimens,populations with unique considerations,pharmacokinetic-informed dosing,body weight factors,pharmacogenetics,and drug–drug interactions are covered.The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy,promoting standardization of MPA TDM,and enhancing treatment efficacy and safety.
文摘BACKGROUND Living donor kidney transplantation is the optimal method of long-term renal replacement therapy.Minimally invasive donor nephrectomy techniques,such as robot-assisted(RALDN)and hand-assisted(HALDN)laparoscopic procedures,are well-established in high-income countries and are being increasingly adopted worldwide.Nevertheless,no studies have reported surgical outcomes of RALDN donor nephrectomy from a United Kingdom center to date.AIM To compare surgical outcomes between RALDN and HALDN laparoscopic donor nephrectomy in a United Kingdom high-volume living kidney donor transplant program.METHODS A case-control matching analysis was performed based on the following parameters:Sex,age,body mass index,procedure laterality,number of renal arteries,and previous abdominal surgeries.Key surgical outcomes,including primary warm ischemia time,operative duration,and post-operative recovery,were evaluated.RESULTS In this cohort of 140 living donors(70 RALDN vs 70 HALDN),donor and recipient outcomes were equivalent across key metrics:Pain scores,overall complication rates,readmissions,reoperations,and creatinine levels at 30 days and 1 year.Recipient long-term renal function did not differ between groups.Operative time for RALDN decreased significantly over the study period,indicating progressive improvement along the learning curve.Although RALDN was associated with a modestly longer mean warm ischaemia time(3.53 minutes vs 2.76 minutes,P<0.001)and extended hospital stay(4.21 days vs 3.17 days,P<0.001),these did not translate into any disadvantage in clinical outcomes.CONCLUSION In this first United Kingdom comparative cohort,RALDN demonstrated excellent safety and efficacy,even in the early phase of our programme,matching the outcomes of the well-established,gold-standard HALDN approach.Moreover,the pronounced learning-curve trajectory suggests considerable potential for further improvements in robotic surgical outcomes as the programme matures.
文摘Ischemia/reperfusion injury is an unavoidable relevant consequence after kidney transplantation and influences short term as well as long-term graft outcome. Clinically ischemia/reperfusion injury is associated with delayed graft function, graft rejection, chronic rejection and chronic graft dysfunction. Ischemia/reperfusion affects many regulatory systems at the cellular level as well as in the renal tissue that result in a distinct inflammatory reaction of the kidney graft. Underlying factors of ischemia reperfusion include energy metabolism, cellular changes of the mitochondria and cellular membranes, initiation of different forms of cell death-like apoptosis and necrosis together with a recently discovered mixed form termed necroptosis. Chemokines and cytokines together with other factors promote the inflammatory response leading to activation of the innate immune system as well as the adaptive immune system. If the inflammatory reaction continues within the graft tissue, a progressive interstitial fibrosis develops that impacts long-term graft outcome. It is of particular importance in kidney transplantation to understand the underlying mechanisms and effects of ischemia/reperfusion on the graft as this knowledge also opens strategies to prevent or treat ischemia/reperfusion injury after transplantation in order to improve graft outcome.
基金Supported by the National Natural Science Foundation of China, No. 30571759Social Development Foundation of Shanghai, No. 200253
文摘AIM. To investigate the influence of heme oxygenase-1 （HO-1） gene transfer on the viability and function of cultured rat islets in vitro. METHODS： Islets were isolated from the pancreata of Sprague-Dawley rats by intraductal collagenase digestion, and purified by discontinuous Ficoll density gradient centrifugation. Purified rat islets were transfected with adenoviral vectors containing human HO-1 gene （Ad- HO-1） or enhanced green fluorescent protein gene （Ad- EGFP）, and then cultured for seven days. Transfection was confirmed by fluorescence microscopy and Western blot. Islet viability was evaluated by acridine orange/ propidium iodide fluorescent staining. Glucose-stimulated insulin release was detected using insulin radioimmunoassay kits and was used to assess the function of islets. Stimulation index （SI） was calculated by dividing the insulin release upon high glucose stimulation by the insulin release upon low glucose stimulation. RESULTS： After seven days culture, the viability of cultured rat islets decreased significantly （92% ± 6% vs 52% ± 13%, P 〈 0.05）, and glucose-stimulated insulin release also decreased significantly （6.47 ± 0.55 mIU/ L/30IEO vs 4.57 ± 0.40 mIU/L/3OIEO., 14.93 ± 1.17 mIU/L/30IEQ vs 9.63 ± 0.71 mIU/L/30IEQ, P 〈 0.05）. Transfection of rat islets with adenoviral vectors at an 1±10 of 20 was efficient, and did not impair islet function. At 7 d post-transfection, the viability of Ad-HO-1 transfected islets was higher than that of control islets（71% ± 15% vs 52% ± 13%, P 〈 0.05）. There was no significant difference in insulin release upon low glucose stimulation （2.8 mmol/L） among Ad-HO-1 transfected group, Ad-EGFP transfected group, and control group （P 〉 0.05）, while when stimulated by high glucose （16.7 mmol/L） solution, insulin release in Ad-HO-1 transfected group was significantly higher than that in Ad-EGFP transfected group and control group, respectively （12.50 ±2.17 mIU/L/30IEQ vs 8.87 ± 0.65 mIU/L/30IEQ, 12.50 ± 2.17 mIU/L/30IEQ vs 9.63 ± 0.71 mIU/L/30IEQ, P 〈 0.05）. The SI of Ad-HO-1 transfected group was also significantly higher than that of Ad-EGFP transfected group and control group, respectively （2.21 ± 0.02 vs 2.08 ± 0.05; 2.21 ± 0.02 vs 2.11 ± 0.03, P 〈 0.05）. CONCLUSION： The viability and function of rat islets decrease over time in in vitro culture, and heine oxygenase-1 gene transfer could improve the viability and function of cultured rat islets.
基金Project supported by the National Natural Science Foundation of China (Nos. 30872578 and 30753761)the Natural Science Founda-tion of Shanxi Province (No. SJ08C201)+1 种基金the Science and Technology Key Projects Foundation of Shanxi Province (No. 2008K13-04)the Science and Technology Plan Projects Foundation of Xi’an (No. SF08006-2), China
文摘Objective: In this paper we compared the two methods of cell sorting (magnetic cell sorting and flow cytometry sorting) for the isolation and function analysis of mouse CD4+ CD25+ regulatory T (Treg) cells, in order to inform further studies in Treg cell function. Methods: We separately used magnetic cell sorting and flow cytometry sorting to identify CD4+ CD25+ Treg cells. After magnetic cell separation, we further used flow cytometry to analyze the purity of CD4+ CD25+ Treg cells, trypan blue staining to detect cell viability, and propidium iodide (PI) staining to assess the cell viability. We detected the immune inhibition of CD4+ CD25+ Treg cells in the in vitro proliferation experiments. Results: The results showed that compared to flow cytometry sorting, magnetic cell sorting took more time and effort, but fewer live cells were obtained than with flow cytometry sorting. The CD4+ CD25+ Treg cells, however, obtained with both methods have similar immunosuppressive capacities. Conclusion: The result suggests that both methods can be used in isolating CD4+ CD25+ Treg cells, and one can select the best method according to specific needs and availability of the methodologies.
文摘Allo-antibodies, particularly when donor specific, are one of the most important factors that cause both early and late graft dysfunction. The authors review the current state of the art concerning this important issue in renal transplantation. Many antibodies have been recognized as mediators of renal injury. In particular donorspecific-Human Leukocyte Antigens antibodies appear to play a major role. New techniques, such as solid phase techniques and Luminex, have revealed these antibodies from patient sera. Other new techniques have uncovered alloantibodies and signs of complement activation in renal biopsy specimens. It has been acknowledged that the old concept of chronic renal injury caused by calcineurine inhibitors toxicity should be replaced in many cases by alloantibodies acting against the graft. In addition, the number of patients on waiting lists with preformed anti-human leukocyte antigens(HLA) antibodies is increasing, primarily from patients with a history of renal transplant failure already been sensitized. We should distinguish early and late acute antibody-mediated rejection from chronic antibody-mediated rejection. The latter often manifets late during the course of the posttransplant period and may be difficult to recognize if specific techniques are not applied. Different therapeutic strategies are used to control antibody-induced damage.These strategies may be applied prior to transplantation or, in the case of acute antibody-mediated rejection, after transplantation. Many new drugs are appearing at the horizon; however, these drugs are far from the clinic because they are in phase Ⅰ-Ⅱ of clinical trials. Thus the pipeline for the near future appears almost empty.
基金Supported by Internal Medicine Department,Joan C Edwards School of Medicine,Marshall University
文摘Synthetic cannabinoids have become a common drug of abuse in recent years and their toxicities have come to light as well. They are known to be notorious for the kidneys, with acute tubular necrosis, acute interstitial nephritis and rhabdomyolysis induced renal injury being the frequent nephrotoxic outcomes in users. We report a case of bilateral renal cortical necrosis, leading to irreversible renal damage and lifelong dialysis dependency.
文摘This review revises the reclassification of the mem-branoproliferative glomerulonephritis （MPGN） after the consensus conference that by 2015 reclassified all the glomerulonephritis basing on etiology and patho-genesis, instead of the histomorphological aspects. After reclassification, two types of MPGN are to date recognized： The immunocomplexes mediated MPGN and the complement mediated MPGN. The latter type is more extensively described in the review either because several of these entities are completely new or because the improved knowledge of the complement cascade allowed for new diagnostic and therapeutic approaches. Overall the complement mediated MPGN are related to acquired or genetic cause. The presence of circulating auto antibodies is the principal acquired cause. Genetic wide association studies and family studies allowed to recognize genetic mutations of different types as causes of the complement dysregulation. The complement cascade is a complex phenomenon and activating factors and regulating factors should be distinguished. Genetic mutations causing abnormalities either in activating or in regulating factors have been described. The diagnosis of the complement mediated MPGN requires a complete study of all these different complement factors. As a consequence, new therapeutic approaches are becoming available. Indeed, in addition to a nonspecifc treatment and to the immunosuppression that has the aim to block the auto antibodies production, the specific inhibition of complement activation is relatively new and may act either blocking the C5 convertase or the C3 convertase. The drugs acting on C3 convertase are still in different phases of clinical development and might represent drugs for the future. Overall the authors consider that one of the principal problems in fnding new types of drugs are both the rarity of the disease and the consequent poor interest in the marketing and the lack of large international cooperative studies.
文摘The recurrence of renal disease after renal transplantation is becoming one of the main causes of graft loss afterkidney transplantation. This principally concerns some of the original diseases as the atypical hemolytic uremic syndrome(HUS), the membranoproliferative glomerulonephritis(MPGN), in particular the MPGN now called C3 glomerulopathy. Both this groups of renal diseases are characterized by congenital(genetic) or acquired(autoantibodies) modifications of the alternative pathway of complement. These abnormalities often remain after transplantation because they are constitutional and poorly influenced by the immunosuppression. This fact justifies the high recurrence rate of these diseases. Early diagnosis of recurrence is essential for an optimal therapeutically approach, whenever possible. Patients affected by end stage renal disease due to C3 glomerulopathies or to atypical HUS, may be transplanted with extreme caution. Living donor donation from relatives is not recommended because members of the same family may be affected by the same gene mutation. Different therapeutically approaches have been attempted either for recurrence prevention and treatment. The most promising approach is represented by complement inhibitors. Eculizumab, a monoclonal antibody against C5 convertase is the most promising drug, even if to date is not known how long the therapy should be continued and which are the best dosing. These facts face the high costs of the treatment. Eculizumab resistant patients have been described. They could benefit by a C3 convertase inhibitor, but this class of drugs is by now the object of randomized controlled trials.
