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Based upon the underlying mechanism and pathological evidence of tissue injury of antibody-mediated rejection (AMR) , four etiological and symptomatic therapies were proposed for managing AMR, including etiological treatment of AMR including antibody-targeting, B cell or plasma cell-targeting therapies; strategies for preventing antibody-mediated endothelial damage: an inhibition of complement/antibody dependent cell-mediated pathways; anticoagulant & thrombolytic therapies for thrombotic microangiopathy secondary to endothelial damage ; anti-inflammatory therapies for acute/chronic vascular inflammation secondary to endothelial damage. Etiological treatment is essential for preventing and treating AMR while symptomatic measures, such as anticoagulant, thrombolytic and antiinflammatory therapies, are stressed. Finally the authors devised therapeutic strategies for AMR in 4 different patient groups of non-sensitized allograft recipients, sensitized allograft recipients, individuals with active AMR and those with chronic active AMR.
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This review summarized the international hot topics and recent advances of donor specific antibody (DSA) and antibody-mediated rejection (AMR) after kidney transplantation, including a novel understanding of DSA, risk stratification, non-HLA antibody impairments, new application strategies of desensitization and AMR treatment, as well as striking a balance between AMR management and infection risk. Also institutional reflections and evaluations were discussed based upon clinical practices.
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With rapid development of organ transplantation, the issue of global organ shortage has become increasingly prominent. At present, liver transplantation is the most effective treatment for end-stage liver disease. Nevertheless, the shortage of donors has been a key problem restricting the development of liver transplantation. China is a country with a larger number of hepatitis B, and the shortage of donor liver is particularly significant. Many critically ill patients often lose the best opportunity or even die because they cannot obtain a matched donor liver in time. As a strategy to expand the donor pool, ABO-incompatible (ABOi) liver transplantation offers new options for patients who are waiting for matched donors. However, ABOi liver transplantation is highly controversial due to higher risk of complications, such as severe infection, antibody-mediated rejection (AMR), biliary complications, thrombotic microangiopathy, and acute kidney injury, etc. In this article, research progress in preoperative, intraoperative and postoperative strategies of ABOi liver transplantation was reviewed, aiming to provide reference for clinical application and research of ABOi liver transplantation.
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Thrombotic microangiopathy (TMA) is a severe complication after kidney transplantation, mainly characterized by thrombocytopenia, microvascular hemolytic anemia and acute kidney injury, which may lead to kidney allograft failure or even death of the recipients. With the increasing quantity of solid organ transplantation in China and deeper understanding of TMA, relevant in-depth studies have been gradually carried out. Kidney transplantation-associated TMA is characterized with different causes and clinical manifestations. Non-invasive specific detection approach is still lacking. The diagnosis of TMA mainly depends on renal biopsy. However, most TMA patients are complicated with significant thrombocytopenia. Hence, renal puncture is a risky procedure. It is difficult to make a definite diagnosis. For kidney transplantation-associated TMA, plasma exchange, intravenous immunoglobulin and withdrawal of potential risk drugs are commonly employed. Nevertheless, the overall prognosis is poor. In this article, the classification of TMA after kidney transplantation, diagnosis and treatment of kidney transplantation-associated TMA were reviewed, aiming to provide reference for clinical diagnosis and treatment of kidney transplantation-associated TMA.
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Kidney transplantation is the optimal treatment for patients with end-stage renal disease, whereas long-term survival of renal allografts remains a challenging issue. Renal ischemia-reperfusion injury (IRI) and rejection of renal allografts are considered as important influencing factors of long-term survival of renal allografts, which are regulated by innate and adaptive immune cells. Macrophages are one type of innate immune cells that could assist initiating adaptive immunity and are divided into M1, M2 and regulatory macrophages. Previous studies have revealed that M1 macrophages may aggravate renal IRI and acute T cell-mediated rejection (TCMR). However, M2 macrophages may mitigate renal IRI and acute TCMR, whereas it is positively correlated with antibody-mediated rejection (AMR). Regulatory macrophages are a special subgroup of macrophages, which may induce immune tolerance in organ transplantation and have promising clinical application prospects and basic scientific research value. In this article, the relationship among macrophage typing, macrophages and renal IRI, rejection of renal allografts, regulatory macrophages and immune tolerance was reviewed, and the potential mechanism was analyzed, aiming to induce changes in macrophage subtypes or eliminate specific subtypes of macrophages, thereby improving clinical prognosis of the recipients and long-term survival of renal allografts.
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Objective:Currently,patients with pre-exsiting donor-specific antibody(DSA)are prone to antibody-mediated rejection(AMR)after surgery and are at a relatively high risk of postoperative complications and graft failure.The risk of postoperative complications and graft failure is relatively high.This study aims to discuss the clinical outcome of DSA-positive kidney transplantation and analyze the role and safety of preoperative pretreatment in DSA-positive kidney transplantation,providing single-center treatment experience for DSA-positive kidney transplantation. Methods:We retrospectively analyzed the clinical data of 15 DSA-positive kidney transplants in the Department of Renal Transplantation of First Affiliated Hospital of Zhengzhou University from August 2017 to July 2022.Eight cases were organ donation after citizen's death(DCD)kidney transplant recipients,of which 3 cases in the early stage were not treated with preoperative desensitisation therapy(DCD untreated group,n=3),and 5 recipients were treated with preoperative rituximab desensitisation(DCD preprocessing group,n=5).The remaining 7 cases were living related donors recipients(LRD)who received preoperative desensitisation treatment with rituximab and plasma exchange(LRD preprocessing group,n=7).We observed and recorded the incidence of complications with changes in renal function and DSA levels in the recipients and the survival of the recipients and transplanted kidneys at 1,3 and 5 years,and to compare the differences in recovery and postoperative complications between 3 groups. Results:All 15 recipients were positive for preoperative panel reactive antibody(PRA)and DSA and were treated with methylprednisolone+rabbit anti-human thymocyte immunoglobulin induction before kidney transplantation.DCD untreated group all suffered from DSA level rebound,delayed renal graft function(DGF)and rejection reaction after surgery.After the combined treatment,DSA level was reduced and the graft renal function returned to normal.The DCD preprocessing group were all without antibody rebound,1 recipient developed DGF and the renal function returned to normal after plasmapheresis,and the remaining 4 recipients recovered their renal function to normal within 2 weeks after the operation.In the LRD preprocessing group,2 cases had antibody rebound and 1 case had rejection,but all of them recovered to normal after treatment,and DSA was maintained at a low level or even disappeared.The incidence of DGF and rejection in the DCD untreated group were significantly higher than that in the DCD preprocessing group and the LRD preprocessing group;and there were no significant difference in the incidence of postoperative haematuria,proteinuria,bacterial and fungal infections,and BK virus infection between the 3 groups(all P>0.05).A total of 11 of the 15 recipients were followed up for more than 1 year,6 for more than 3 years,and 1 for more than 5 years,and the survival rates of both the recipients and the transplanted kidneys were 100%. Conclusion:Effective preoperative pretreatment with desensitization therapy can effectively prevent antibody rebound in DSA-positive kidney transplantation and reduce perioperative complications.
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One case of de novo donor specific antibody(dnDSA)mediated rejection after pediatric kidney transplantation(KT)was analyzed retrospectively.The risk factors and prevention procedures associated with dnDSA induction, and the clinical features and protocols for late post-transplant antibody-mediated rejection(AMR)in pediatric patients were presented.
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Contexto el rechazo crónico mediado por anticuerpos (cABMR, chronic antibody-mediated rejection) se considera una de las principales causas de disfunción crónica del injerto. Objetivo profundizar en la comprensión de los mecanismos que la ocasionan para diseñar tratamientos efectivos, dado que es muy poco lo que se ha avanzado en el tratamiento de esta patología. Metodología en esta revisión narrativa de la literatura, presentamos los factores de riesgo relacionados con la disfunción crónica del injerto, haciendo énfasis en la fisiopatología, el diagnóstico y el tratamiento del cABMR. Resultados el factor de riesgo más relevante para el desarrollo de disfunción crónica del injerto es el desarrollo de anticuerpos donante específicos (DSA) y ABMR. Para el diagnóstico de cABMR activo, se requieren los criterios de Banff 2017 (los tres deben estar presentes: Evidencia histológica de lesión tisular crónica, evidencia de inflamación actual en el endotelio vascular ocasionada por anticuerpos y evidencia serológica de DSA. El cABMR no tiene un tratamiento efectivo. Conclusiones dado que cABMR no tiene un tratamiento efectivo, es importante disminuir la exposición a los factores de riesgo y hacer un diagnóstico y un tratamiento oportuno de los eventos agudos de lesión renal que contribuyen a la progresión de disfunción crónica del injerto.
Context Chronic antibody-mediated rejection (cABMR) is considered one of the main causes of chronic graft. Objective To review the mechanisms that cause cABMR to design effective treatments, since it is very little what has been advanced in it treatment of this pathology. Methodology In this narrative review of the literature, we present the risk factors related to the chronic dysfunction of the injection, emphasizing the pathophysiology the diagnosis and treatment of cABMR. Results The most relevant risk factor for the development of chronic graft dysfunction is the development of specific donor antibodies (DSA) and ABMR. For the diagnosis of active cABMR, the criteria of Banff 2017 are required (three must be present: histological evidence of chronic tissue injury, evidence of current inflammation in the vascular endothelium caused by antibodies and serological evidence of DSA. The cABMR does not have an effective treatment. Conclusions Since cABMR does not have an effective treatment, it is important reduce exposure to risk factors and carry out a diagnosis and treatment of the acute events of kidney injury that contribute to the progression of chronic injection dysfunction.
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In recent years, the quantity of lung transplantation has been gradually increased in China along with the accumulation of surgical techniques and postoperative management experience of lung transplantation. Multiple lung allograft complications may occur after lung transplantation, mainly including primary graft dysfunction (PGD) caused by ischemia-reperfusion injury (IRI) of the lung allograft, acute and chronic rejection, opportunistic infection or lymphoproliferative disorder of lymphoid tissues induced by the decrease of host immunity due to postoperative use of immunosuppressants, etc. The diagnosis of complications after lung transplantation mainly relies on biopsy of the lung allograft. In this article, the brief history of lung allograft pathology, main approaches and pathological processing techniques of lung allograft biopsy, major complications after lung transplantation and pathological diagnostic criteria were elucidated, aiming to provide reference for targeted management of these complications in clinical practice.
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Composite tissue allotransplantation (CTA) is a novel transplantation discipline to treat functional tissue or limb defects. Since a majority of CTA grafts were vascularized grafts, it is also known as vascularized composite allotransplantation (VCA). The grafts of CTA/VCA consist of two or more types of allogeneic skin, subcutaneous tissue, bone, muscle, nerve and vessel, etc. Most of CTA/VCA grafts contain skin tissues, which possess the highest antigenicity. Acute rejection after transplantation is the primary obstacle leading to CTA/VCA graft failure and primary graft dysfunction. Hence, histopathological characteristics of skin rejection in CTA/VCA grafts have become the primary hotspot. In this article, pathological features of CTA/VCA rejection, Banff classification in 2007 and related research progress were reviewed, aiming to provide reference for the diagnosis and treatment of rejection and other complications of CTA/VCA.
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Early diagnosis and treatment of rejection after kidney transplantation play a critical role in alleviating allograft injury. Detection of donor-derived cell-free DNA (dd-cfDNA) could be performed based on the next-generation sequencing and other techniques. The content of DNA fragments derived from necrotic and apoptotic donor kidney tissues in circulating body fluids could be determined by concentration and absolute quantitative methods, which has application potential in monitoring allograft injury in clinical practice. Compared with traditional serum creatinine and other indicators, dd-cfDNA detection may monitor allograft injury from several weeks to months in advance, providing a "time window" for clinical treatment and delaying graft failure. Along with deepening research of dd-cfDNA in recent years, dd-cfDNA has captivated widespread attention due to its non-invasiveness, high sensitivity and real-time evaluation of therapeutic effect. In this article, current study evidence and conclusions related to multidimensional application of dd-cfDNA detection in diagnosis and treatment of kidney transplantation were reviewed, and the future research and clinical application direction of dd-cfDNA were discussed, aiming to provide reference for widespread application of dd-cfDNA detection in clinical practice in China.
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Objective To investigate the treatment on de novo donor specific antibody (dnDSA) mediated acute rejection after lung transplantation. Methods Clinical data of 1 recipient with antibody-mediated rejection (AMR) early after lung transplantation was retrospectively analyzed. The process of diagnosis and treatment were assessed. Results The recipient underwent right lung transplantation due to systemic sclerosis-associated end-stage interstitial lung disease. Preoperatively, classⅠ panel reactive antibody (PRA) was positive (11%). No pretreatment was given before transplantation. Antithymocyte globulin induction therapy was delivered on the day of transplantation and postoperatively. The recipient was properly recovered early after transplantation. Chest tightness and shortness of breath occurred at postoperative 13 d, which were progressively worsened and rapidly progressed into type Ⅰ respiratory failure. Class Ⅰ PRA was increased to 58%, and dnDSA was observed at the loci of A24: 02. The mean fluorescence intensity (MFI) was 2 110. According to the guidelines of International Society for Heart and Lung Transplantation, the recipient was diagnosed as possible AMR. After comprehensive treatment including plasmapheresis, protein A immunoadsorption, glucocorticoid pulse, rituximab and immunoglobulin intravenous drip, the PRA and DSA levels were gradually decreased, and the MFI of DSA was 0 at postoperative 20 d. Clinical condition of the recipient was gradually improved. The dyspnea was healed, shortness of breath was eased, respiratory failure was treated, and pulmonary effusion was gradually absorbed. At postoperative 45 d, the recipient was discharged after full recovery. During 1-year follow-up, the recipient was physically stable and obtained normal quality of life. Class Ⅰ PRA was 5%, and class Ⅱ PRA was negative. No DSA was noted. Conclusions Based on traditional drug therapy, supplement of protein A immunoadsorption therapy may effectively eliminate DSA from the circulating blood of the recipient and mitigate the damage of target organs. Ideal short- and long-term prognosis may be achieved. Traditional drug therapy combined with immunoadsorption may yield ideal efficacy in treating AMR after lung transplantation.
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In recent years, pediatric kidney transplantation has developed rapidly in China. However, clinical data related to the long-term survival of renal allografts are still lacking. The production of de novo donor specific antibody (dnDSA)and its mediated chronic rejection after adult kidney transplantation are pivotal risk factors affecting the long-term survival of renal allografts. Nevertheless, immune system in children has not fully developed. Hence, the production of dnDSA after kidney transplantation and its influence upon renal allografts and recipients might differ from those of adult. In this article, the characteristics of pediatric immune system, the production and influence of donor specific antibody (DSA) after pediatric kidney transplantation and the risk factors of the production of DSA after pediatric kidney transplantation were reviewed and certain suggestions were proposed for prevention strategies, aiming to provide reference for prolonging the long-term survival of renal allografts after pediatric kidney transplantation and promote the development of pediatric kidney transplantation in China.
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Over the past 70 years, kidney transplantation has become not only the most mature but also the highest-success-rate surgery among all organ transplantation surgeries. However, the long-term survival of kidney transplant recipients is still challenged by such key factors as ischemia-reperfusion injury related to kidney transplantation, rejection, chronic renal allograft dysfunction, renal allograft fibrosis, immunosuppressive therapy, infections and others. Relevant fundamental and clinical studies have emerged endlessly. At the same time, the research related to kidney transplantation also becomes a new hot spot accordingly in the context of the normalization of novel coronavirus pneumonia. This article reviewed the cutting-edge hot spots in relation to the fundamental and clinical aspects of kidney transplantation together with relevant new techniques and new visions. The studies included in this article focused on the reports published by Chinese teams that are more applicable to the current situation of kidney transplantation in China, for the purpose of providing new thoughts and strategies for the diagnosis and treatment of kidney transplantation related issues in China.
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Pancreas transplantation and pancreas-kidney transplantation are the optimal treatment for renal failure caused by type 1 diabetes mellitus, partial type 2 diabetes mellitus and their complications. Pancreas transplantation mainly includes simultaneous pancreas-kidney transplantation (SPK), pancreas transplantation after kidney transplantation (PAK) and pancreas transplantation alone (PTA). Among all types of pancreas transplantation, biopsy of pancreas allograft remains the best method for definitively diagnosing rejection and differentiate it from other complications. In this article, biopsy methods of pancreas allograft and related research progress, diagnostic criteria and research progress on rejection of pancreas allograft biopsy, and main complications and pathological manifestations of pancreas allograft were illustrated, aiming to provide reference for guiding the clinical diagnosis of the above mentioned complications and ensuring the long-term survival of pancreas allografts and recipients.
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Antibody-mediated rejection (AMR) is the primary factor affecting the long-term prognosis of kidney transplant recipients and kidney allograft. Currently, there is no universally recognized or approved drug for the treatment of AMR. Therefore, more novel drug studies and clinical trials are urgently needed in order to change the long-term prognosis of kidney transplant recipients. Based on the core principles of prevention and treatment of AMR, this paper discusses the mechanism and efficacy of several new types of drugs of most concern in the treatment of AMR from three aspects: removing donor specific antibody, blocking antibody-mediated and complement-mediated tissue damage, and inhibiting the proliferation and activation of antibody-producing cells. These emerging drugs have shown potential in preventing and treating AMR and improving the prognosis of recipients, which is expected to change the dilemma of AMR treatment in the future and provide more effective treatment options for improving the long-term prognosis of kidney transplant recipients.
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La hipertensión arterial pulmonar (HAP) representa el 2,6% de los trasplantes pulmonares (TP), con una mediana de supervivencia condi cional (desde los 30 días del TP) de 9,8 años. Son frecuentes, el rechazo celular agudo (ACR) y la disfunción crónica del injerto (CLAD), mientras que es infrecuente el rechazo mediado por anticuerpos (AMR). El retrasplante pulmonar (RTP) constituye el 4% del TP mundial, debido a complicaciones en la vía aérea, disfunción primaria del injerto, ACR y CLAD. Mujer de 22 años, portadora de HAP idiopática (HAPI) desde el año 2013, trasplantada bipulmonar (TBP) en enero de 2018. A los 16 meses presentó neumonía adquirida en la comuni dad. En una internación posterior, presentó ACR y a pesar de pulsos de metilprednisolona, progresó a requerimientos de cánula de alto flujo y ventilación mecánica no invasiva hospitalaria, caída del VEF1, y tomografía de tórax con vidrio esmerilado difuso y engrosamiento irregular reticular del intersticio subpleural; interpretándose como CLAD a predominio de síndrome de bronquiolitis obliterante (BOS), con presencia de anticuerpos específicos contra el donante (DSA). En enero de 2020 se realizó nuevo TP y ante cross-match positivo, se realizó plasmaféresis y reposición de IgG. Al mes del egreso, no se observaron signos de rechazo en control de biopsias transbronquiales. Entre 2 y 10% de los pacientes con indicación primaria de TP por HAPI son sometidos a retrasplante pulmonar (RTP). La presencia de DSA y el miss-match de HLA, no son contraindicaciones para el RTP.
Pulmonary arterial hypertension (PAH) represents 2.6% of lung transplantations (LT), with a conditional median survival (from 30 days after LT) of 9.8 years. Acute cellular rejection (ACR) and chronic lung allograft dysfunction (CLAD) are common; whereas the antibody-mediated rejection (AMR) is not. Lung retransplantation (LR) accounts for 4% of global LTs for complications in the airways, primary allograft dys function, ACR and CLAD. 22-year-old woman with idiopathic PAH (IPAH) since 2013, who underwent a double-lung transplantation (DLT) in January 2018. 16 months after transplantation she presented community-acquired pneumonia. During a subsequent hospitalization, she presented ACR. Despite the fact that she received pulse methylprednisolone, she required high-flow cannula therapy and hospital non-invasive mechanical ventilation; the FEV1 was reduced and she underwent a chest tomography with diffuse ground glass opacities and irregular reticular thickening of the subpleural interstitium; interpreting the predominance of BOS (bronchiolitis obliterans syndrome) as CLAD, with presence of donor-specific antibodies (DSA). In January 2020, she received a new DLT and due to a positive crossmatch, she was treated with plasmapheresis and IgG replacement. One month after hospital discharge, no signs of rejection were observed at the BTB (bone-patellar tendon-bone) control. Between 2 to 10% of patients with primary indication of LT for IPAH are subjected to lung retransplantation (LR). The presence of DSA and HLA (human leucocyte antigen) mismatch aren't contraindications to LR.
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The Banff conference on allograft pathology (Banff conference) and the establishment of Banff classification on allograft pathology (Banff classification) are milestones in the development of international allograft pathology. At present, all organ transplantation centers around the world routinely perform pathological diagnosis by biopsy of the transplant kidney according to Banff classification. Subsequently, the consensus process and update mode of Banff classification for transplant kidney was quickly extended to transplant heart, lung, liver, pancreas, and small intestine, etc. The Banff conference has not only become a thematic meeting that includes the pathology study and discussion of various transplant organs, but also gradually developed unified diagnostic standard for the biopsy of each transplant organ, which better promoted the accurate diagnosis and treatment of complications after organ transplantation. This article summarized the history of international allograft pathology research, the Banff conference and Banff classification in promoting organ transplantation, which aimed to provide a reference for the smooth development of clinical organ transplantation.
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The American Transplant Congress (ATC) is an annual international academic conference in the field of transplantation, which includes the latest achievements of scholars around the world in transplantation, and also leads the frontier direction of transplantation research. In this paper, the international forefront hotspots in basic and translational medicine research associated with renal transplantation in 2020 ATC were summarized, including the new discoveries of memory cell function and immune memory mechanism, the latest discovery in the mechanism of rejection and immune tolerance, the current research status of xenotransplantation, the potential solutions of antibody-mediated rejection (AMR), and the application of nanomedicine and single-cell RNA sequencing in renal transplantation, etc.
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T cell-mediated rejection (TCMR) is one of the main mechanisms of rejection in organ transplantation, which is also the most common type of acute rejection.Based on Banff classification on allograft pathology (Banff classification) in 2019, TCMR can be divided into acute TCMR (aTCMR) and chronic active TCMR (caTCMR) according to the characteristics of immune lesions.In this article, the basic definition of TCMR, the research progress on TCMR pathology according to Banff classification for renal allograft, and the basic pathological changes and diagnostic grading of TCMR were reviewed, aiming to provide evidence for early identification, diagnosis and treatment of TCMR and prevent the progression of TCMR into caTCMR, thereby guarantying the long-term survival of both the renal allograft and recipient.