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
The new kidney allocation scheme(KAS) in effect since December 4th 2014 was designed to overcome the shortcomings of previous system. A key feature of the new KAS is preferential allocation of best quality organs to w...The new kidney allocation scheme(KAS) in effect since December 4th 2014 was designed to overcome the shortcomings of previous system. A key feature of the new KAS is preferential allocation of best quality organs to wait-list candidates with the longest predictivesurvival in a concept called longevity matching. Highly sensitized recipients would get extra points and enjoy widespread sharing of organs in order to increase accessibility to transplant. Wait-list candidates with blood group B will be offered organs from donors with A2 and A2 B blood type in order to shorten their wait-list time. Time on the wait list will start from day of listing or date of initiation of dialysis whichever comes first which should benefit candidates with limited resources who might be late to get on the transplant list. Pay back system has been eliminated in the new KAS. These changes in organ allocation policy may lead to increase in median half-life of the allograft and increase the number of transplants; thus resulting in better utilization of a scarce resource. There could be unintended negative consequences which may become evident over time.展开更多
Calcineurin inhibitors(CNIs) represent today a cornerstone for the maintenance immunosuppressive treatment in solid organ transplantation. Nevertheless, several attempts have been made either to minimize their dosage ...Calcineurin inhibitors(CNIs) represent today a cornerstone for the maintenance immunosuppressive treatment in solid organ transplantation. Nevertheless, several attempts have been made either to minimize their dosage or to avoid CNIs at all because these drugs have the severe side effect of chronic nephrotoxicity. This issue represents a frontier for renal transplantation. The principal problem is to understanding whether the poor outcome over the long-term may be ascribed to CNIs nephrotoxicity or to the inability of these drugs to control the acute and chronic rejection B cells mediated. The authors analyze extensively all the international trials attempting to withdraw, minimize or avoid the use of CNIs. Few trials undertaken in low risk patients with an early conversion from CNIs to proliferation signal inhibitors were successful, but the vast majority of trials failed to improve CNIs side effects. To date the use of a new drug, a co-stimulation blocker, seems promising in avoiding CNIs with similar efficacy, better glomerular filtration rate and an improved metabolic profile. Moreover the use of this drug is not associated with the development of donorspecific anti-human leukocyte antigen antibodies. Thispoint has a particular relevance, because the failure of CNIs to realize good outcomes in renal transplantation has recently ascribed to their inability to control the acute and chronic rejections B-cell mediated. This paper analyzes all the recent studies that have been done on this issue that represents the real frontier that should be overcome to realize better results over the long-term after transplantation.展开更多
With the support by the National Natural Science Foundation of China and the Ministry of Science and Technology of China,the research team led by Prof.Zhang HaoLi(张浩力)at the State Key Laboratory of Applied Organic ...With the support by the National Natural Science Foundation of China and the Ministry of Science and Technology of China,the research team led by Prof.Zhang HaoLi(张浩力)at the State Key Laboratory of Applied Organic Chemistry,Key Laboratory of Special Function Materials and Structure Design,College of Chemistry and Chemical Engineering,Lanzhou University,developed a new design strategy for donor material toward high-performance all-small-molecule organic solar cells,which was published in Chemistry of Materials(2018,30:8661一8668).展开更多
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.
文摘The new kidney allocation scheme(KAS) in effect since December 4th 2014 was designed to overcome the shortcomings of previous system. A key feature of the new KAS is preferential allocation of best quality organs to wait-list candidates with the longest predictivesurvival in a concept called longevity matching. Highly sensitized recipients would get extra points and enjoy widespread sharing of organs in order to increase accessibility to transplant. Wait-list candidates with blood group B will be offered organs from donors with A2 and A2 B blood type in order to shorten their wait-list time. Time on the wait list will start from day of listing or date of initiation of dialysis whichever comes first which should benefit candidates with limited resources who might be late to get on the transplant list. Pay back system has been eliminated in the new KAS. These changes in organ allocation policy may lead to increase in median half-life of the allograft and increase the number of transplants; thus resulting in better utilization of a scarce resource. There could be unintended negative consequences which may become evident over time.
文摘Calcineurin inhibitors(CNIs) represent today a cornerstone for the maintenance immunosuppressive treatment in solid organ transplantation. Nevertheless, several attempts have been made either to minimize their dosage or to avoid CNIs at all because these drugs have the severe side effect of chronic nephrotoxicity. This issue represents a frontier for renal transplantation. The principal problem is to understanding whether the poor outcome over the long-term may be ascribed to CNIs nephrotoxicity or to the inability of these drugs to control the acute and chronic rejection B cells mediated. The authors analyze extensively all the international trials attempting to withdraw, minimize or avoid the use of CNIs. Few trials undertaken in low risk patients with an early conversion from CNIs to proliferation signal inhibitors were successful, but the vast majority of trials failed to improve CNIs side effects. To date the use of a new drug, a co-stimulation blocker, seems promising in avoiding CNIs with similar efficacy, better glomerular filtration rate and an improved metabolic profile. Moreover the use of this drug is not associated with the development of donorspecific anti-human leukocyte antigen antibodies. Thispoint has a particular relevance, because the failure of CNIs to realize good outcomes in renal transplantation has recently ascribed to their inability to control the acute and chronic rejections B-cell mediated. This paper analyzes all the recent studies that have been done on this issue that represents the real frontier that should be overcome to realize better results over the long-term after transplantation.
文摘With the support by the National Natural Science Foundation of China and the Ministry of Science and Technology of China,the research team led by Prof.Zhang HaoLi(张浩力)at the State Key Laboratory of Applied Organic Chemistry,Key Laboratory of Special Function Materials and Structure Design,College of Chemistry and Chemical Engineering,Lanzhou University,developed a new design strategy for donor material toward high-performance all-small-molecule organic solar cells,which was published in Chemistry of Materials(2018,30:8661一8668).
