The combination of kidney paired donation(KPD) with desensitization represents a promising method of increasing the rate of living donor kidney transplantation(LDKT) in immunologically challenging patients. Patients w...The combination of kidney paired donation(KPD) with desensitization represents a promising method of increasing the rate of living donor kidney transplantation(LDKT) in immunologically challenging patients. Patients who are difficult to match and desensitize due to strong donor specific antibody are may be transplanted by a combination of desensitization and KPD protocol with more immunologically favorable donor. We present our experience of combination of desensitization protocol with three-way KPD which contributed to successful LDKT in highly sensitized end stage renal disease patient. All recipients were discharged with normal and stable allograft function at 24 mo follow up. We believe that this is first report from India where three-way KPD exchange was performed with the combination of KPD and desensitization. The combination of desensitization protocol with KPD improves access and outcomes of LDKT.展开更多
A literature review on immune monitoring in kidney transplantation produced dozens of research articles and a multitude of promising biomarkers,all in the quest for the much sought after-but perennially elusive-"...A literature review on immune monitoring in kidney transplantation produced dozens of research articles and a multitude of promising biomarkers,all in the quest for the much sought after-but perennially elusive-"holy grail" of kidney biomarkers able to unequivocally predict acute transplant rejection vs non-rejection.Detection methodologies and study designs were many and varied.Hence the motivation for this editorial,which espouses the notion that in today's kidney transplantation milieu,the judicious use of disease classifiers tailored to specific patient immune risks may be more achievable and productive in the long run and confer a greater advantage for patient treatment than the pursuit of a single "omniscient" biomarker.In addition,we desire to direct attention toward greater scrutiny of biomarker publications and decisions to implement biomarkers in practice,standardization of methods in the development of biomarkers and consideration for adoption of "biomarker-driven" biopsies.We propose "biomarkerdriven" biopsies as an adjunctive to and/or alternative to random surveillance(protocol) biopsies or belated indication biopsies.The discovery of a single kidney transplantation biomarker would represent a major breakthrough in kidney transplantation practice,but until that occurs-if ever it does occur,other approaches offer substantial potential for unlocking prognostic,diagnostic and therapeutic options.We conclude our editorial with suggestions and recommendations for productively incorporating current biomarkers into diagnostic algorithms and for testing future biomarkers of acute rejection in kidney transplantation.展开更多
One of the principal obstacles in transplantation from living donors is that approximately 30%are immunologically incompatible because of the presence in the recipient of antibodies directed against the human leukocyt...One of the principal obstacles in transplantation from living donors is that approximately 30%are immunologically incompatible because of the presence in the recipient of antibodies directed against the human leukocyte antigen system of the donor or because of the incompatibility of the ABO system.The aim of this review is to describe the more recent data from the literature on the different protocols used and the clinical outcomes of ABO-incompatible kidney transplantation.Two different strategies are used to overcome these barriers:desensitization of the recipient to remove the antibodies and to prevent their rebound after transplantation and the exchange of organs between two or more pairs.The largest part of this review is dedicated to describing the techniques of desensitization.Even if the first reports of successful renal transplantation between ABO-incompatible pairs have been published by 1980,the number of ABO-incompatible transplants increased substantially in this century because of our improved knowledge of the immune system and the availability of new drugs.Rituximab has substantially replaced splenectomy.The technique of apheresis has improved and more recently a tailored desensitization proved to be the more efficient strategy avoiding an excess of immunosuppression with the related side effects.Recent reports document outcomes for such transplantation similar to the outcomes of standard transplantation.展开更多
Background:Although ABO-incompatible(ABOi)kidney transplantation(KT)has been performed successfully,a standard preconditioning regimen has not been established.Based on the initial antidonor ABO antibody titers,an ind...Background:Although ABO-incompatible(ABOi)kidney transplantation(KT)has been performed successfully,a standard preconditioning regimen has not been established.Based on the initial antidonor ABO antibody titers,an individualized preconditioning regimen is developed,and this study explored the efficacy and safety of the regimen.Methods:From September 1,2014,to September 1,2020,we performed 1668 consecutive living-donor KTs,including 100 ABOi and 1568 ABO-compatible(ABOc)KTs.ABOi KT recipients(KTRs)with a lower antibody titer(≤1:8)were administered oral immunosuppressive drugs(OIs)before KT,while patients with a medium titer(1:16)received OIs plus antibody-removal therapy(plasma exchange/double-filtration plasmapheresis),patients with a higher titer(≥1:32)were in addition received rituximab(Rit).Competing risk analyses were conducted to estimate the cumulative incidence of infection,acute rejection(AR),graft loss,and patient death.Results:After propensity score analyses,100 ABOi KTRs and 200 matched ABOc KTRs were selected.There were no significant differences in graft and patient survival between the ABOi and ABOc groups(P=0.787,P=0.386,respectively).After using the individualized preconditioning regimen,ABOi KTRs showed a similar cumulative incidence of AR(10.0%vs.10.5%,P=0.346).Among the ABOi KTRs,the Rit-free group had a similar cumulative incidence of AR(P=0.714)compared to that of the Rittreated group.Multivariate competing risk analyses revealed that a Rit-free regimen reduced the risk of infection(HR:0.31;95%CI:0.12–0.78,P=0.013).Notably,antibody titer rebound was more common in ABOi KTRs receiving a Rit-free preconditioning regimen(P=0.013)than those receiving Rit.ABOi KTRs with antibody titer rebound had a 2.72-fold risk of AR(HR:2.72,95%CI:1.01–7.31,P=0.048).ABOi KTRs had similar serum creatinine and estimated glomerular filtration rate compared to those of ABOc KTRs after the first year.Conclusions:An individualized preconditioning regimen can achieve comparable graft and patient survival rates in ABOi KT with ABOc KT.Rit-free preconditioning effectively prevented AR without increasing the risk of infectious events in those with lower initial titers;however,antibody titer rebound should be monitored.展开更多
文摘The combination of kidney paired donation(KPD) with desensitization represents a promising method of increasing the rate of living donor kidney transplantation(LDKT) in immunologically challenging patients. Patients who are difficult to match and desensitize due to strong donor specific antibody are may be transplanted by a combination of desensitization and KPD protocol with more immunologically favorable donor. We present our experience of combination of desensitization protocol with three-way KPD which contributed to successful LDKT in highly sensitized end stage renal disease patient. All recipients were discharged with normal and stable allograft function at 24 mo follow up. We believe that this is first report from India where three-way KPD exchange was performed with the combination of KPD and desensitization. The combination of desensitization protocol with KPD improves access and outcomes of LDKT.
文摘A literature review on immune monitoring in kidney transplantation produced dozens of research articles and a multitude of promising biomarkers,all in the quest for the much sought after-but perennially elusive-"holy grail" of kidney biomarkers able to unequivocally predict acute transplant rejection vs non-rejection.Detection methodologies and study designs were many and varied.Hence the motivation for this editorial,which espouses the notion that in today's kidney transplantation milieu,the judicious use of disease classifiers tailored to specific patient immune risks may be more achievable and productive in the long run and confer a greater advantage for patient treatment than the pursuit of a single "omniscient" biomarker.In addition,we desire to direct attention toward greater scrutiny of biomarker publications and decisions to implement biomarkers in practice,standardization of methods in the development of biomarkers and consideration for adoption of "biomarker-driven" biopsies.We propose "biomarkerdriven" biopsies as an adjunctive to and/or alternative to random surveillance(protocol) biopsies or belated indication biopsies.The discovery of a single kidney transplantation biomarker would represent a major breakthrough in kidney transplantation practice,but until that occurs-if ever it does occur,other approaches offer substantial potential for unlocking prognostic,diagnostic and therapeutic options.We conclude our editorial with suggestions and recommendations for productively incorporating current biomarkers into diagnostic algorithms and for testing future biomarkers of acute rejection in kidney transplantation.
文摘One of the principal obstacles in transplantation from living donors is that approximately 30%are immunologically incompatible because of the presence in the recipient of antibodies directed against the human leukocyte antigen system of the donor or because of the incompatibility of the ABO system.The aim of this review is to describe the more recent data from the literature on the different protocols used and the clinical outcomes of ABO-incompatible kidney transplantation.Two different strategies are used to overcome these barriers:desensitization of the recipient to remove the antibodies and to prevent their rebound after transplantation and the exchange of organs between two or more pairs.The largest part of this review is dedicated to describing the techniques of desensitization.Even if the first reports of successful renal transplantation between ABO-incompatible pairs have been published by 1980,the number of ABO-incompatible transplants increased substantially in this century because of our improved knowledge of the immune system and the availability of new drugs.Rituximab has substantially replaced splenectomy.The technique of apheresis has improved and more recently a tailored desensitization proved to be the more efficient strategy avoiding an excess of immunosuppression with the related side effects.Recent reports document outcomes for such transplantation similar to the outcomes of standard transplantation.
基金National Natural Science Foundation of China(Nos.81870513,81600584)the Sichuan Science and Technology Program(No.2019YJ0133)+1 种基金the Chengdu Science and Technology Program(No.2019-YF05-00084-SN)1.3.5 Project for Disciplines of Excellence Clinical Research Incubation Project,West China Hospital,Sichuan University(Nos.2018HXFH049,ZY2016104,2021HXFH007)。
文摘Background:Although ABO-incompatible(ABOi)kidney transplantation(KT)has been performed successfully,a standard preconditioning regimen has not been established.Based on the initial antidonor ABO antibody titers,an individualized preconditioning regimen is developed,and this study explored the efficacy and safety of the regimen.Methods:From September 1,2014,to September 1,2020,we performed 1668 consecutive living-donor KTs,including 100 ABOi and 1568 ABO-compatible(ABOc)KTs.ABOi KT recipients(KTRs)with a lower antibody titer(≤1:8)were administered oral immunosuppressive drugs(OIs)before KT,while patients with a medium titer(1:16)received OIs plus antibody-removal therapy(plasma exchange/double-filtration plasmapheresis),patients with a higher titer(≥1:32)were in addition received rituximab(Rit).Competing risk analyses were conducted to estimate the cumulative incidence of infection,acute rejection(AR),graft loss,and patient death.Results:After propensity score analyses,100 ABOi KTRs and 200 matched ABOc KTRs were selected.There were no significant differences in graft and patient survival between the ABOi and ABOc groups(P=0.787,P=0.386,respectively).After using the individualized preconditioning regimen,ABOi KTRs showed a similar cumulative incidence of AR(10.0%vs.10.5%,P=0.346).Among the ABOi KTRs,the Rit-free group had a similar cumulative incidence of AR(P=0.714)compared to that of the Rittreated group.Multivariate competing risk analyses revealed that a Rit-free regimen reduced the risk of infection(HR:0.31;95%CI:0.12–0.78,P=0.013).Notably,antibody titer rebound was more common in ABOi KTRs receiving a Rit-free preconditioning regimen(P=0.013)than those receiving Rit.ABOi KTRs with antibody titer rebound had a 2.72-fold risk of AR(HR:2.72,95%CI:1.01–7.31,P=0.048).ABOi KTRs had similar serum creatinine and estimated glomerular filtration rate compared to those of ABOc KTRs after the first year.Conclusions:An individualized preconditioning regimen can achieve comparable graft and patient survival rates in ABOi KT with ABOc KT.Rit-free preconditioning effectively prevented AR without increasing the risk of infectious events in those with lower initial titers;however,antibody titer rebound should be monitored.
