No validated system currently exists to realistically characterize the chronic pathology of kidney transplants that represents the dynamic disease process and spectrum of disease severity. We sought to develop and validate a tool to describe chronicity and severity of renal allograft disease and integrate it with the evaluation of disease activity.

The training cohort included 3549 kidney transplant biopsies from an observational cohort of 937 recipients. We reweighted the chronic histologic lesions according to their time-dependent association with graft failure, and performed consensus k-means clustering analysis. Total chronicity was calculated as the sum of the weighted chronic lesion scores, scaled to the unit interval.

We identified four chronic clusters associated with graft outcome, based on the proportion of ambiguous clustering. The two clusters with the worst survival outcome were determined by interstitial fibrosis and tubular atrophy (IFTA) and by transplant glomerulopathy. The chronic clusters partially overlapped with the existing Banff IFTA classification (adjusted Rand index, 0.35) and were distributed independently of the acute lesions. Total chronicity strongly associated with graft failure (hazard ratio [HR], 8.33; 95% confidence interval [CI], 5.94 to 10.88; P<0.001), independent of the total activity scores (HR, 5.01; 95% CI, 2.83 to 7.00; P<0.001). These results were validated on an external cohort of 4031 biopsies from 2054 kidney transplant recipients.

The evaluation of total chronicity provides information on kidney transplant pathology that complements the estimation of disease activity from acute lesion scores. Use of the data-driven algorithm used in this study, called RejectClass, may provide a holistic and quantitative assessment of kidney transplant injury phenotypes and severity.

目前没有经过验证的系统可以真实地描述代表动态疾病过程和疾病严重程度范围的肾移植的慢性病理学。我们试图开发和验证一种工具来描述同种异体移植肾疾病的长期性和严重性，并将其与疾病活动性的评估相结合。

训练队列包括来自 937 名接受者的观察队列的 3549 份肾移植活检。我们根据慢性组织学损伤与移植物失败的时间依赖性关联对慢性组织学损伤进行了重新加权，并进行了一致的k均值聚类分析。总慢性化计算为加权慢性病变评分的总和，按单位间隔缩放。

我们根据模糊聚类的比例确定了四个与移植结果相关的慢性聚类。生存结果最差的两个集群由间质纤维化和肾小管萎缩 (IFTA) 以及移植肾小球病确定。慢性集群与现有的班夫 IFTA 分类（调整后的兰德指数，0.35）部分重叠，并且独立于急性病变分布。与移植失败密切相关的总慢性化（风险比 [HR]，8.33；95% 置信区间 [CI]，5.94 至 10.88；P <0.001），独立于总活动评分（HR，5.01；95% CI，2.83 至7.00；P <0.001）。这些结果在来自 2054 名肾移植受者的 4031 份活检的外部队列中得到验证。

总慢性化的评估提供了肾移植病理学的信息，补充了根据急性损伤评分估计疾病活动性。使用本研究中使用的数据驱动算法，称为 RejectClass，可以提供对肾移植损伤表型和严重程度的整体和定量评估。