Suhail Sufi M
Department of Renal Medicine, Singapore General Hospital, Singapore 169856, Singapore.
World J Transplant. 2022 Jun 18;12(6):112-119. doi: 10.5500/wjt.v12.i6.112.
End-stage kidney failure (ESKD) is a global issue where kidney replacement therapy imposes enormous economic burden to people of developing countries, in addition to the severe limitations to the availability of hemodialysis and peritoneal dialysis technique. The best option of kidney transplantation also requires lifelong combination immunosuppressive medicines, the cost of which is equally comparable to lifelong dialysis. A strategy of achieving transplant tolerance that requires minimum immunosuppressive medicines, although in experimental stage, also requires state-of-art technology with costly medicines and interventions. This is evidently beyond the reach of ESKD patients of developing countries. Hence, globally in developing countries, a need for an innovative but cost-effective tolerance protocol is a burning need for a successful transplant program. In brief, transplant tolerance is defined as a state of donor-specific unresponsiveness to the allograft antigens without the need for ongoing pharmacologic immunosuppression or with a minimal need. Current state-of-art techniques involves: (1) A state of hematological chimera, for complete tolerance; (2) Prope or partial tolerance where immune-reactive T-lymphocytes are inhibited using monoclonal antibodies; and (3) Chimeric antigen receptor for T-regulatory (T-reg) cell therapy using genetically engineered T-reg cells targeting specific T-lymphocyte receptors for inducing anergy. From our real-world experience in transplant management in post-transplant lympho-proliferative disorders (PTLD), we noticed frequently a drastic reduction in the need of immunosuppressive medicines following lympho-ablative therapy for PTLD. We recently published a case study on a real-world experience transplant case where we explained a partial or prope tolerance that developed after lymphocyte ablation therapy, following which the allograft was maintained with low dose dual standard immunosuppressive medicines. Based on this publication, we propose here an innovative tolerance protocol for living related low risk kidney transplantation for developing countries, in this opinion review.
终末期肾衰竭(ESKD)是一个全球性问题,肾脏替代疗法给发展中国家的人们带来了巨大的经济负担,此外,血液透析和腹膜透析技术的可及性也受到严重限制。肾脏移植的最佳选择还需要终身联合使用免疫抑制药物,其成本与终身透析相当。实现移植耐受的策略,即只需最少的免疫抑制药物,尽管仍处于实验阶段,但也需要先进的技术以及昂贵的药物和干预措施。这显然超出了发展中国家ESKD患者的承受能力。因此,在全球范围内的发展中国家,对于一个成功的移植项目而言,迫切需要一种创新且具有成本效益的耐受方案。简而言之,移植耐受被定义为对同种异体移植抗原产生供体特异性无反应状态,无需持续的药物免疫抑制或只需极少的此类抑制。当前的先进技术包括:(1)血液学嵌合体状态,以实现完全耐受;(2)前耐受或部分耐受,即使用单克隆抗体抑制免疫反应性T淋巴细胞;(3)用于调节性T(T-reg)细胞治疗的嵌合抗原受体,使用基因工程改造靶向特定T淋巴细胞受体的T-reg细胞来诱导无反应性。从我们在移植后淋巴增殖性疾病(PTLD)移植管理的实际经验中,我们经常注意到,对PTLD进行淋巴细胞清除治疗后,免疫抑制药物的需求大幅减少。我们最近发表了一篇关于一个实际移植病例的案例研究,其中解释了淋巴细胞清除治疗后出现的部分或前耐受情况,之后使用低剂量的两种标准免疫抑制药物维持同种异体移植。基于此发表内容,在本观点综述中,我们为发展中国家提出一种针对亲属活体低风险肾脏移植的创新耐受方案。