AbstractAIM： To investigate the impact of minimum tacrolimus（TAC） on new-onset diabetes mellitus （NODM） afterliver transplantation （LT）.METHODS： We retrospectively analyzed the data of973 liver transplant reci...AbstractAIM： To investigate the impact of minimum tacrolimus（TAC） on new-onset diabetes mellitus （NODM） afterliver transplantation （LT）.METHODS： We retrospectively analyzed the data of973 liver transplant recipients between March 1999and September 2014 in West China Hospital LiverTransplantation Center. Following the exclusion ofineligible recipients, 528 recipients with a TAC-dominantregimen were included in our study. We calculatedand determined the mean trough concentration ofTAC （cTAC） in the year of diabetes diagnosis in NODMrecipients or in the last year of the follow-up in non-NODM recipients. A cutoff of mean cTAC value forpredicting NODM 6 mo after LT was identified usinga receptor operating characteristic curve. TAC-relatedcomplications after LT was evaluated by χ^2 test, andthe overall and allograft survival was evaluated usingthe Kaplan-Meier method. Risk factors for NODM afterLT were examined by univariate and multivariate Cox regression.RESULTS： Of the 528 transplant recipients, 131（24.8%） developed NODM after 6 mo after LT, andthe cumulative incidence of NODM progressivelyincreased. The mean cTAC of NODM group recipientswas significantly higher than that of recipients in thenon-NODM group （7.66 ± 3.41 ng/mL vs 4.47 ± 2.22ng/mL, P 〈 0.05）. Furthermore, NODM group recipientshad lower 1-, 5-, 10-year overall survival rates （86.7%,71.3%, and 61.1% vs 94.7%, 86.1%, and 83.7%, P 〈0.05） and allograft survival rates （92.8%, 84.6%, and75.7% vs 96.1%, 91%, and 86.1%, P 〈 0.05） thanthe others. The best cutoff of mean cTAC for predictingNODM was 5.89 ng/mL after 6 mo after LT. Multivariateanalysis showed that old age at the time of LT （〉 50years）, hypertension pre-LT, and high mean cTAC （≥5.89 ng/mL） after 6 mo after LT were independent riskfactors for developing NODM. Concurrently, recipientswith a low cTAC （〈 5.89 ng/mL） were less likely tobecome obese （21.3% vs 30.2%, P 〈 0.05） or todevelop dyslipidemia （27.5% vs 44.8%, P 〈0.05）,chronic kidney dysfunction （14.6% vs 22.7%, P 〈 0.05）,and moderate to severe infection （24.7% vs 33.1%, P〈 0.05） after LT than recipients in the high mean cTACgroup. However, the two groups showed no significantdifference in the incidence of acute and chronicrejection, hypertension, cardiovascular events and newonsetmalignancy.CONCLUSION： A minimal TAC regimen can decreasethe risk of long-term NODM after LT. Maintaining a cTACvalue below 5.89 ng/mL after LT is safe and beneficial.展开更多
Type 1 diabetes mellitus(T1DM)is one of the important causes of chronic kidney disease(CKD)and end-stage renal failure(ESRF).Even with the best available treatment options,management of T1DM poses significant challeng...Type 1 diabetes mellitus(T1DM)is one of the important causes of chronic kidney disease(CKD)and end-stage renal failure(ESRF).Even with the best available treatment options,management of T1DM poses significant challenges for clinicians across the world,especially when associated with CKD and ESRF.Substantial increases in morbidity and mortality along with marked rise in treatment costs and marked reduction of quality of life are the usual consequences of onset of CKD and progression to ESRF in patients with T1DM.Simultaneous pancreas-kidney transplant(SPK)is an attractive and promising treatment option for patients with advanced CKD/ESRF and T1DM for potential cure of these diseases and possibly several complications.However,limited availability of the organs for transplantation,the need for long-term immunosuppression to prevent rejection,peri-and post-operative complications of SPK,lack of resources and the expertise for the procedure in many centers,and the cost implications related to the surgery and postoperative care of these patients are major issues faced by clinicians across the globe.This clinical update review compiles the latest evidence and current recommendations of SPK for patients with T1DM and advanced CKD/ESRF to enable clinicians to care for these diseases.展开更多
Simultaneous liver,pancreas-duodenum,and kidney transplantation has been rarely reported in the literature. Here we present a new and more efficient en bloc technique that combines classic orthotopic liver and pancrea...Simultaneous liver,pancreas-duodenum,and kidney transplantation has been rarely reported in the literature. Here we present a new and more efficient en bloc technique that combines classic orthotopic liver and pancreas-duodenum transplantation and heterotopic kidney transplantation for a male patient aged 44 years who had hepatitis B related cirrhosis,renal failure,and insulin dependent diabetes mellitus(IDDM). A quadruple immunosuppressive regimen including induction with basiliximab and maintenance therapy with tacrolimus,mycophenolate mofetil,and steroids was used in the early stage post-transplant. Postoperative recovery was uneventful and the patient was discharged on the 15 th postoperative day with normal liver and kidney function. The insulin treatment was completely withdrawn 3 wk after operation,and the blood glucose level remained normal. The case findings support that abdominal organ cluster and kidney transplantation is an effective method for the treatment of end-stage liver disease combined with uremia and IDDM.展开更多
Although,liver transplantation serves as the only curative treatment for patients with end-stage liver diseases,it is burdened with complications,which affect survival rates.In addition to clinical risk factors,contri...Although,liver transplantation serves as the only curative treatment for patients with end-stage liver diseases,it is burdened with complications,which affect survival rates.In addition to clinical risk factors,contribution of recipient and donor genetic prognostic markers has been extensively studied in order to reduce the burden and improve the outcomes.Determination of single nucleotide polymorphisms(SNPs)is one of the most important tools in development of personalized transplant approach.To provide a better insight in recent developments,we review the studies published in the last three years that investigated an association of recipient or donor SNPs with most common issues in liver transplantation:Acute cellular rejection,development of new-onset diabetes mellitus and non-alcoholic fatty liver disease,hepatocellular carcinoma recurrence,and tacrolimus concentration variability.Reviewed studies confirmed previously established SNP prognostic factors,such as PNPLA3 rs738409 for nonalcoholic fatty liver disease development,or the role of CYP3A5 rs776746 in tacrolimus concentration variability.They also identified several novel SNPs,with a reasonably strong association,which have the potential to become useful predictors of post-transplant complications.However,as the studies were typically conducted in one center on relatively low-to-moderate number of patients,verification of the results in other centers is warranted to resolve these limitations.Furthermore,of 29 reviewed studies,28 used gene candidate approach and only one implemented a genome wide association approach.Genome wide association multicentric studies are needed to facilitate the development of personalized transplant medicine.展开更多
Kidney transplantation is the treatment of choice for management of end-stage renal disease.However,in diabetic patients,the underlying metabolic disturbance will persist and even may get worse after isolated kidney t...Kidney transplantation is the treatment of choice for management of end-stage renal disease.However,in diabetic patients,the underlying metabolic disturbance will persist and even may get worse after isolated kidney transplantation.Pancreatic transplantation in humans was first introduced in 1966.The initial outcome was disappointing.However,this was changed after the improvement of surgical techniques together with better patient selection and the availability of potent and better-tolerated immune-suppression like cyclosporine and induction antibodies.Combined kidney and pancreas transplantation will not only solve the problem of organ failure,but it will also stabilise or even reverse the metabolic complications of diabetes.Combined kidney and pancreas transplantation have the best long term outcome in diabetic cases with renal failure.Nevertheless,at the cost of an initial increase in morbidity and risk of mortality.Other transplantation options include pancreas after kidney transplantation and islet cell transplantation.We aim by this work to explore various options which can be offered to a diabetic patient with advanced chronic kidney disease.Our work will provide a simplified,yet up-to-date information regarding the different management options for those diabetic chronic kidney failure patients.展开更多
BACKGROUND Physical activity levels are significantly lower in kidney transplant(KT)recipients compared to the general population.The effects of exercise training in KT recipients with diabetes mellitus remain unclear...BACKGROUND Physical activity levels are significantly lower in kidney transplant(KT)recipients compared to the general population.The effects of exercise training in KT recipients with diabetes mellitus remain unclear,and so little is known about the role of increased exercise on cardiovascular risk and metabolic profile of KT patients.AIM To investigate the effects of a 6-mo home-based exercise training program on functional capacity,glucose levels and lipid profile of diabetic KT patients.METHODS In total,21 type II diabetic KT recipients were randomly assigned into two groups:Exercise(n=11,aged 52.9±10.1 years)and control(n=10,aged 53.01±9.5 years).All participants at baseline and the end of the study underwent biochemical tests for fasting plasma glucose levels,glycated hemoglobin and lipid profile and cardiopulmonary exercise testing for maximum oxygen uptake[(VO2)peak]estimation.The exercise group followed a 6-mo supervised home-based aerobic and progressive resistance exercise program of moderate intensity 3 times per week,while the control group continued to receive usual care.RESULTS At the end of the 6-mo study,the exercise group had significantly lower values in fasting plasma glucose by 13.4%(from 120.6±28.9 mg/dL to 104.8±21.9 mg/dL,P=0.01),glycated hemoglobin by 1.5%(from 6.7%±0.4 to 6.6%±0.4,P=0.01)and triglycerides by 8.5%(from 164.7±14.8 mg/dL to 150.8±11.6 mg/dL,P<0.05)and higher values in high-density lipoprotein by 10.2%(from 51.4±8.8 mg/dL to 57.2±8.7 mg/dL,P<0.05)and(VO_(2))_(peak)by 4.7%(from 22.7±3.3 to 23.8±4.2,P=0.02)than the control group.There were statistically significant differences between the two groups at the end of the study for fasting plasma glucose(decreased by 9.6%,P<0.05),triglycerides(decreased by 4.5%,P=0.04)and(VO_(2))_(peak)(increased by 4.4%,P=0.01).Finally,after training,there was a moderate,positive linear relationship between(VO_(2))_(peak)and glycated hemoglobin in the exercise group(r=0.408,P=0.03).CONCLUSION The results demonstrated that a 6-mo home-based mixed type exercise training program can improve the functional capacity,levels of glucose and lipid profile of diabetic KT recipients.展开更多
基金Supported by Key Technology Support Program of Sichuan ProvinceNo.2013SZ0023
文摘AbstractAIM： To investigate the impact of minimum tacrolimus（TAC） on new-onset diabetes mellitus （NODM） afterliver transplantation （LT）.METHODS： We retrospectively analyzed the data of973 liver transplant recipients between March 1999and September 2014 in West China Hospital LiverTransplantation Center. Following the exclusion ofineligible recipients, 528 recipients with a TAC-dominantregimen were included in our study. We calculatedand determined the mean trough concentration ofTAC （cTAC） in the year of diabetes diagnosis in NODMrecipients or in the last year of the follow-up in non-NODM recipients. A cutoff of mean cTAC value forpredicting NODM 6 mo after LT was identified usinga receptor operating characteristic curve. TAC-relatedcomplications after LT was evaluated by χ^2 test, andthe overall and allograft survival was evaluated usingthe Kaplan-Meier method. Risk factors for NODM afterLT were examined by univariate and multivariate Cox regression.RESULTS： Of the 528 transplant recipients, 131（24.8%） developed NODM after 6 mo after LT, andthe cumulative incidence of NODM progressivelyincreased. The mean cTAC of NODM group recipientswas significantly higher than that of recipients in thenon-NODM group （7.66 ± 3.41 ng/mL vs 4.47 ± 2.22ng/mL, P 〈 0.05）. Furthermore, NODM group recipientshad lower 1-, 5-, 10-year overall survival rates （86.7%,71.3%, and 61.1% vs 94.7%, 86.1%, and 83.7%, P 〈0.05） and allograft survival rates （92.8%, 84.6%, and75.7% vs 96.1%, 91%, and 86.1%, P 〈 0.05） thanthe others. The best cutoff of mean cTAC for predictingNODM was 5.89 ng/mL after 6 mo after LT. Multivariateanalysis showed that old age at the time of LT （〉 50years）, hypertension pre-LT, and high mean cTAC （≥5.89 ng/mL） after 6 mo after LT were independent riskfactors for developing NODM. Concurrently, recipientswith a low cTAC （〈 5.89 ng/mL） were less likely tobecome obese （21.3% vs 30.2%, P 〈 0.05） or todevelop dyslipidemia （27.5% vs 44.8%, P 〈0.05）,chronic kidney dysfunction （14.6% vs 22.7%, P 〈 0.05）,and moderate to severe infection （24.7% vs 33.1%, P〈 0.05） after LT than recipients in the high mean cTACgroup. However, the two groups showed no significantdifference in the incidence of acute and chronicrejection, hypertension, cardiovascular events and newonsetmalignancy.CONCLUSION： A minimal TAC regimen can decreasethe risk of long-term NODM after LT. Maintaining a cTACvalue below 5.89 ng/mL after LT is safe and beneficial.
文摘Type 1 diabetes mellitus(T1DM)is one of the important causes of chronic kidney disease(CKD)and end-stage renal failure(ESRF).Even with the best available treatment options,management of T1DM poses significant challenges for clinicians across the world,especially when associated with CKD and ESRF.Substantial increases in morbidity and mortality along with marked rise in treatment costs and marked reduction of quality of life are the usual consequences of onset of CKD and progression to ESRF in patients with T1DM.Simultaneous pancreas-kidney transplant(SPK)is an attractive and promising treatment option for patients with advanced CKD/ESRF and T1DM for potential cure of these diseases and possibly several complications.However,limited availability of the organs for transplantation,the need for long-term immunosuppression to prevent rejection,peri-and post-operative complications of SPK,lack of resources and the expertise for the procedure in many centers,and the cost implications related to the surgery and postoperative care of these patients are major issues faced by clinicians across the globe.This clinical update review compiles the latest evidence and current recommendations of SPK for patients with T1DM and advanced CKD/ESRF to enable clinicians to care for these diseases.
基金Supported by National Natural Science Foundation of China,No.81400680Tianjin Natural Science Foundation,No.17JCQNJC12800
文摘Simultaneous liver,pancreas-duodenum,and kidney transplantation has been rarely reported in the literature. Here we present a new and more efficient en bloc technique that combines classic orthotopic liver and pancreas-duodenum transplantation and heterotopic kidney transplantation for a male patient aged 44 years who had hepatitis B related cirrhosis,renal failure,and insulin dependent diabetes mellitus(IDDM). A quadruple immunosuppressive regimen including induction with basiliximab and maintenance therapy with tacrolimus,mycophenolate mofetil,and steroids was used in the early stage post-transplant. Postoperative recovery was uneventful and the patient was discharged on the 15 th postoperative day with normal liver and kidney function. The insulin treatment was completely withdrawn 3 wk after operation,and the blood glucose level remained normal. The case findings support that abdominal organ cluster and kidney transplantation is an effective method for the treatment of end-stage liver disease combined with uremia and IDDM.
基金the Croatian Science Foundation grant“The Role of Notch Signalling Pathway in Pathogenesis of Hepatic Fibrosis”,No.UIP-2017-05-1965.
文摘Although,liver transplantation serves as the only curative treatment for patients with end-stage liver diseases,it is burdened with complications,which affect survival rates.In addition to clinical risk factors,contribution of recipient and donor genetic prognostic markers has been extensively studied in order to reduce the burden and improve the outcomes.Determination of single nucleotide polymorphisms(SNPs)is one of the most important tools in development of personalized transplant approach.To provide a better insight in recent developments,we review the studies published in the last three years that investigated an association of recipient or donor SNPs with most common issues in liver transplantation:Acute cellular rejection,development of new-onset diabetes mellitus and non-alcoholic fatty liver disease,hepatocellular carcinoma recurrence,and tacrolimus concentration variability.Reviewed studies confirmed previously established SNP prognostic factors,such as PNPLA3 rs738409 for nonalcoholic fatty liver disease development,or the role of CYP3A5 rs776746 in tacrolimus concentration variability.They also identified several novel SNPs,with a reasonably strong association,which have the potential to become useful predictors of post-transplant complications.However,as the studies were typically conducted in one center on relatively low-to-moderate number of patients,verification of the results in other centers is warranted to resolve these limitations.Furthermore,of 29 reviewed studies,28 used gene candidate approach and only one implemented a genome wide association approach.Genome wide association multicentric studies are needed to facilitate the development of personalized transplant medicine.
文摘Kidney transplantation is the treatment of choice for management of end-stage renal disease.However,in diabetic patients,the underlying metabolic disturbance will persist and even may get worse after isolated kidney transplantation.Pancreatic transplantation in humans was first introduced in 1966.The initial outcome was disappointing.However,this was changed after the improvement of surgical techniques together with better patient selection and the availability of potent and better-tolerated immune-suppression like cyclosporine and induction antibodies.Combined kidney and pancreas transplantation will not only solve the problem of organ failure,but it will also stabilise or even reverse the metabolic complications of diabetes.Combined kidney and pancreas transplantation have the best long term outcome in diabetic cases with renal failure.Nevertheless,at the cost of an initial increase in morbidity and risk of mortality.Other transplantation options include pancreas after kidney transplantation and islet cell transplantation.We aim by this work to explore various options which can be offered to a diabetic patient with advanced chronic kidney disease.Our work will provide a simplified,yet up-to-date information regarding the different management options for those diabetic chronic kidney failure patients.
文摘BACKGROUND Physical activity levels are significantly lower in kidney transplant(KT)recipients compared to the general population.The effects of exercise training in KT recipients with diabetes mellitus remain unclear,and so little is known about the role of increased exercise on cardiovascular risk and metabolic profile of KT patients.AIM To investigate the effects of a 6-mo home-based exercise training program on functional capacity,glucose levels and lipid profile of diabetic KT patients.METHODS In total,21 type II diabetic KT recipients were randomly assigned into two groups:Exercise(n=11,aged 52.9±10.1 years)and control(n=10,aged 53.01±9.5 years).All participants at baseline and the end of the study underwent biochemical tests for fasting plasma glucose levels,glycated hemoglobin and lipid profile and cardiopulmonary exercise testing for maximum oxygen uptake[(VO2)peak]estimation.The exercise group followed a 6-mo supervised home-based aerobic and progressive resistance exercise program of moderate intensity 3 times per week,while the control group continued to receive usual care.RESULTS At the end of the 6-mo study,the exercise group had significantly lower values in fasting plasma glucose by 13.4%(from 120.6±28.9 mg/dL to 104.8±21.9 mg/dL,P=0.01),glycated hemoglobin by 1.5%(from 6.7%±0.4 to 6.6%±0.4,P=0.01)and triglycerides by 8.5%(from 164.7±14.8 mg/dL to 150.8±11.6 mg/dL,P<0.05)and higher values in high-density lipoprotein by 10.2%(from 51.4±8.8 mg/dL to 57.2±8.7 mg/dL,P<0.05)and(VO_(2))_(peak)by 4.7%(from 22.7±3.3 to 23.8±4.2,P=0.02)than the control group.There were statistically significant differences between the two groups at the end of the study for fasting plasma glucose(decreased by 9.6%,P<0.05),triglycerides(decreased by 4.5%,P=0.04)and(VO_(2))_(peak)(increased by 4.4%,P=0.01).Finally,after training,there was a moderate,positive linear relationship between(VO_(2))_(peak)and glycated hemoglobin in the exercise group(r=0.408,P=0.03).CONCLUSION The results demonstrated that a 6-mo home-based mixed type exercise training program can improve the functional capacity,levels of glucose and lipid profile of diabetic KT recipients.
