Understanding the Causes of Kidney Transplant Failure: The Dominant Role of Antibody-Mediated Rejection and Nonadherence
Understanding the Causes of Kidney Transplant Failure: The Dominant Role of Antibody-Mediated Rejection and Nonadherence
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DOI：
10.1111/j.1600-6143.2011.03840.x
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发表时间：
2012-02-01
影响因子：
8.8
通讯作者：
Halloran, P. F.
中科院分区：
文献类型：
--
作者：
Sellares, J.;de Freitas, D. G.;Halloran, P. F.
我们前瞻性地研究了临床适应症活检后进展为失败的肾移植，旨在为每一个失败分配一个原因。我们随访了315位同种异体移植受者，他们在移植后6天至32年接受了指征活检。在随访期间（中位31.4个月），60例肾脏进展为衰竭。失败在t细胞介导的排斥反应和急性肾损伤后很少见，而在抗体介导的排斥反应或肾小球肾炎后很常见。我们制定了使用活检诊断、HLA抗体和临床数据来解释每个失败的规则。排除信息缺失的4例，56例失败可归因于4种原因：排斥反应36例（64%），肾小球肾炎10例（18%），多瘤病毒肾病4例（7%）和并发事件6例（11%）。每次排异反应失败时都有抗体介导的排异反应的证据。在排异反应损失中，36例患者中有17例（47%）被主治临床医生独立认定为不依从。进展到失败的患者（32%）比存活的患者（3%）更容易出现不依从。纯t细胞介导的排斥反应、急性肾损伤、药物毒性和不明原因的进行性纤维化都不是损失的原因。这一前瞻性队列研究表明，许多指征活检后的实际失败表现出抗体介导或混合排斥的表型特征，也强调了不依从性的主要作用。
We prospectively studied kidney transplants that progressed to failure after a biopsy for clinical indications, aiming to assign a cause to every failure. We followed 315 allograft recipients who underwent indication biopsies at 6 days to 32 years posttransplant. Sixty kidneys progressed to failure in the follow-up period (median 31.4 months). Failure was rare after T-cellmediated rejection and acute kidney injury and common after antibody-mediated rejection or glomerulonephritis. We developed rules for using biopsy diagnoses, HLA antibody and clinical data to explain each failure. Excluding four with missing information, 56 failures were attributed to four causes: rejection 36 (64%), glomerulonephritis 10 (18%), polyoma virus nephropathy 4 (7%) and intercurrent events 6 (11%). Every rejection loss had evidence of antibody-mediated rejection by the time of failure. Among rejection losses, 17 of 36 (47%) had been independently identified as nonadherent by attending clinicians. Nonadherence was more frequent in patients who progressed to failure (32%) versus those who survived (3%). Pure T-cellmediated rejection, acute kidney injury, drug toxicity and unexplained progressive fibrosis were not causes of loss. This prospective cohort indicates that many actual failures after indication biopsies manifest phenotypic features of antibody-mediated or mixed rejection and also underscores the major role of nonadherence.