Einecke G, Reeve J, Halloran P F
Department of Nephrology, Hannover Medical School, Hannover, Germany.
Alberta Transplant Applied Genomics Centre, Edmonton, AB, Canada.
Am J Transplant. 2017 May;17(5):1346-1357. doi: 10.1111/ajt.14136. Epub 2017 Jan 3.
Because calcineurin inhibitor (CNI) immunosuppressive drugs induce arteriolar hyalinosis (ah) in kidney transplants, ah lesions can potentially provide information about drug exposure. We studied the relationship of ah lesions to findings and outcomes in 562 indication biopsies taken 3 days to 35 years after transplant. Prevalence of ah lesions increased with time of biopsy after transplant (TxBx). The ah scores correlated with arterial intimal thickening and atrophy-fibrosis but, unlike atrophy-fibrosis, did not increase until after 500 days because of a background of ah1 lesions in early biopsies reflecting donor aging. Correlation of ah scores with other features varied with TxBx-in early biopsies, donor age and related changes, and in very late biopsies, chronic antibody-mediated rejection and glomerulonephritis and associated lesions. After correction for TxBx, ah0 in intermediate time periods was associated with increased risk of T cell-mediated rejection and graft loss, probably because of underimmunosuppression and nonadherence. Thus, ah lesions in indication biopsies have multiple associations: donor age (early, usually ah1), chronic glomerular diseases (late, often ah2/3), and adequate exposure to CNIs at intermediate times. This threefold TxBx-dependent complexity must be considered when interpreting indication biopsies: ah lesions often indicate adequate CNI exposure, not toxicity, and unexpected ah0 should increase vigilance for nonadherence and underimmunosuppression.
由于钙调神经磷酸酶抑制剂（CNI）免疫抑制药物会在肾移植中引发小动脉玻璃样变（ah），因此ah病变可能会提供有关药物暴露的信息。我们研究了562例移植后3天至35年进行的指征性活检中ah病变与检查结果及预后的关系。ah病变的患病率随移植后活检时间（TxBx）的增加而升高。ah评分与动脉内膜增厚和萎缩-纤维化相关，但与萎缩-纤维化不同的是，由于早期活检中反映供体老化的ah1病变背景，ah评分直到500天后才升高。ah评分与其他特征的相关性随TxBx而变化——在早期活检中，与供体年龄及相关变化有关；在极晚期活检中，与慢性抗体介导的排斥反应、肾小球肾炎及相关病变有关。校正TxBx后，中期的ah0与T细胞介导的排斥反应和移植物丢失风险增加相关，这可能是由于免疫抑制不足和不依从性导致的。因此，指征性活检中的ah病变有多种关联：供体年龄（早期，通常为ah1）、慢性肾小球疾病（晚期，通常为ah2/3）以及中期对CNIs的充分暴露。解读指征性活检时必须考虑这种依赖TxBx的三重复杂性：ah病变通常表明CNI暴露充分，而非毒性作用，意外出现的ah0应提高对不依从性和免疫抑制不足的警惕。
