Early Diagnosis and Treatment of Subclinical AMR Is Vital for Improving Clinical Outcomes

亚临床感染 医学 血浆置换术 美罗华 肾移植 移植 无症状的 免疫抑制 重症监护医学 供体特异性抗体 内科学 抗体 免疫学
作者
Dominik Chittka
出处
期刊:Transplantation [Wolters Kluwer]
卷期号:103 (8): 1542-1543 被引量:3
标识
DOI:10.1097/tp.0000000000002567
摘要

Despite remarkable improvements in short-term outcomes of kidney grafts over the last decade, long-term outcomes have not significantly changed. About one-third of all transplanted patients will lose their graft within 10 years.1 We now know that the majority of late allograft loss results from cumulative effects of underlying subacute immunological injury and that such processes often remain undetected until irreversible damage has already occurred.2 Late irreversible graft failure is typically associated with antibody-mediated responses, which are now the greatest unsolved problem in improving kidney transplant outcomes. None of the current treatment options for clinical antibody-mediated rejection (AMR) (including steroids, plasmapheresis, application of IVIGs or rituximab) have been able to significantly improve outcomes; therefore, new diagnostic and therapeutic strategies are urgently needed.3 Subclinical antibody-mediated rejection is defined by histological signs of AMR without impairment of graft function, with or without detection of donor-specific antibodies. In the largest reported cohort of 1001 kidney transplant recipients, 14% were diagnosed with subclinical AMR.4 Diagnosis of subclinical AMR is associated with poor long-term outcomes and independently associated with graft loss.4 In this issue of Transplantation, a paper by Parajuli et al5 investigates whether early diagnosis and treatment of subclinical AMR can slow progression to clinical AMR. In their study, protocol biopsies were performed at 3 months and 1 year posttransplant, which allowed patients with stable graft function to be classified as subclinical AMR or nonrejecting. Twenty-five patients with subclinical AMR were treated with intravenous steroids, IVIG, plasmapheresis, and rituximab, according to the standard of care for patients with clinical AMR. Graft function and failure rates were similar between treated subclinical AMR and the rejection-negative control group, whereas both were significantly worse in the clinical AMR group. Although the study did not randomize subclinical AMR patients to intervention versus nonintervention, considering the known deleterious effects of subclinical AMR, the authors claim that early diagnosis and intensified treatment are beneficial for long-term outcomes. If these results can be confirmed in a prospective, randomized clinical trial, they could lead to a change in treatment strategy. On the other hand, one must consider the potential risk of overimmunosuppression and associated side effects like infectious complications in patients with a stable graft function. This is an important question that could also be addressed by an adequately designed prospective study. Parajuli's study emphasizes the importance of early detection of histological changes before irreversible graft damage occurs. Some predictive biomarkers like donor-specific cell-free DNA have shown very promising results and could potentially serve as predictors of AMR and success of treatment in the near future.6 But as long as these markers have not been validated in larger cohorts to be accepted as a standard diagnostic approach, protocol biopsies are the only way to detect such early changes in patients with serologically normal graft function. A recent survey of US transplant centers showed that only 17% perform regular surveillance biopsies on all patients.7 Unexpectedly, Parajuli's report also suggests that early intervention in subclinical AMR improves outcomes, whereas the course of clinical AMR cannot be altered. In future prospective studies, it would be valuable if the success of treatment were confirmed by follow-up biopsies. Notably, in cases of cellular rejection, it is reported that patients with recurrent subclinical changes (meaning that the histological signs are found in a follow-up biopsy despite adequate initial therapy) do worse than patients with resolved signs of rejection. Although the detrimental impact of de novo donor-specific antibody (dnDSA) and subclinical AMR on kidney graft outcomes is well-described,4 the significance of dnDSA in the setting of stable transplant function without histological signs of AMR is still discussed as being controversial. In some studies, emergence of dnDSA has been associated with higher rates of subclinical and clinical AMR and worse long-term outcomes8,9; however, others report dnDSA is a benign finding that is not associated with deterioration in graft function as long as there are no signs of rejection.10 Importantly, Parajuli's study included a control group of donor-specific antibody-positive patients (both de novo and preexisting) and did not receive treatment. This subgroup had better outcomes than patients with clinical AMR but worse than patients with treated subclinical AMR (figure 2). Hence, the presence of dnDSA seems to have an impact on graft function even in patients with stable graft function at the time of detection. In summary, Parajuli et al's work speaks to the importance of early diagnosis and treatment of subclinical AMR, but the results must be further confirmed by a prospective trial in which patients with subclinical AMR are randomized to continued or intensified treatment arms.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
大大怪将军完成签到,获得积分10
1秒前
哈哈哈完成签到 ,获得积分0
1秒前
小怪完成签到,获得积分10
2秒前
爱吃泡芙完成签到,获得积分10
3秒前
白桃战士完成签到,获得积分10
4秒前
6秒前
qingchenwuhou完成签到 ,获得积分10
6秒前
XXX完成签到,获得积分10
7秒前
锡嘻完成签到 ,获得积分10
7秒前
8秒前
彗星入梦完成签到 ,获得积分10
8秒前
恋恋青葡萄完成签到,获得积分10
8秒前
隐形万言完成签到,获得积分10
10秒前
Time完成签到,获得积分10
10秒前
土木研学僧完成签到,获得积分10
11秒前
yjy完成签到 ,获得积分10
11秒前
A溶大美噶完成签到,获得积分10
11秒前
yar应助萨尔莫斯采纳,获得10
12秒前
Will发布了新的文献求助10
12秒前
美好的鹏笑完成签到,获得积分10
14秒前
啦啦啦啦啦完成签到,获得积分10
14秒前
LYegoist完成签到,获得积分10
16秒前
可爱的小丸子完成签到,获得积分10
16秒前
一川烟叶完成签到,获得积分10
18秒前
18秒前
21秒前
iFan完成签到 ,获得积分10
21秒前
萨尔莫斯完成签到,获得积分10
21秒前
合适靖儿完成签到 ,获得积分10
23秒前
林林林完成签到,获得积分10
24秒前
斯琪欣完成签到,获得积分10
25秒前
26秒前
MQQ完成签到 ,获得积分10
26秒前
meng发布了新的文献求助10
26秒前
27秒前
zxc167完成签到,获得积分10
27秒前
研友_nVWP2Z完成签到 ,获得积分10
29秒前
俭朴的半雪完成签到 ,获得积分10
30秒前
大橙子发布了新的文献求助10
31秒前
meng完成签到,获得积分10
32秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Handbook of Industrial Diamonds.Vol2 1100
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038201
求助须知:如何正确求助?哪些是违规求助? 3575940
关于积分的说明 11373987
捐赠科研通 3305747
什么是DOI,文献DOI怎么找? 1819274
邀请新用户注册赠送积分活动 892662
科研通“疑难数据库(出版商)”最低求助积分说明 815022