中药致急性肾小管间质性肾炎临床病理特点分析

Clinicopathological characteristics of herbal medicine-induced acute tubulointerstitial nephritis

目的分析中药致药物相关性急性肾小管间质性肾炎（drug-induced acute tubulointerstitial nephritis，D-ATIN）的临床病理特点以及预后情况。方法回顾性分析2002年1月至2013年1月北京大学第一医院肾内科经临床病理确诊的119例D-ATIN患者临床及随访资料，入选11例单纯应用中药致D-ATIN患者为中药组，并选择同期的10例β内酰胺类抗生素致D-ATIN的患者为抗生素组，进行临床病理特征及预后分析。结果中药组患者以女性（10／11）为主。与β内酰胺类致D-ATIN组患者相比，中药组患者过敏反应少见，用药时间及患者开始用药至临床发病的时间较长。2组患者全身炎症反应以及肾功能损害程度（血肌酐水平）无统计学差异，但中药致D-ATIN患者尿N-乙酰-D葡萄糖酐转化酶（N—acetyl-β-D-glucosaminidase，NAG）以及微量白蛋白水平（micro-albumi，mAlb）均显著低于抗生素组患者[NAG：18（12．5，19．5）比28（14，72．5），P：0．05；mAlb：62．4（47，85．6）比107（76．4，172．5），P=0．031]。2组患者肾脏病理急性评分没有明显差异；中药组患者慢性病变评分（包括肾小管萎缩和肾间质纤维化）明显高于抗生素组[1．0（0，1．0）比0（0，0），P=0．033]。随访1个月和1年时中药致D-ATIN患者的估计肾小球滤过率均小于内酰胺类抗生素致D-ATIN患者[1个月时：（40．1±19．6）ml·min·（1．73m2）。比（50．8±15．8）ml·min·（1．73m2）-1，P=0．207）；1年时：（64．9±21．7）ml·min·（1．73m2）-1比（73．1±24．5）ml·min·（1．73m2）-1，P=0．448）]，但无统计学差异。结论中药致D-ATIN的患者起病隐袭，容易延误诊断。临床医生应提高警惕，减少不必要用药并加强对用药人群的肾损害监测。

Objective To study^the clinicopathological characteristics and renal outcome of herbal medicine-induced acute tubulointerstitial nephritis （Herbal-DATIN）. Methods Eleven cases of Herbal- DATIN were enrolled from a cohort of clinicopathologically diagnosed DATIN in Peking University First Hospital. Ten cases of-Lactam antibiotics-induced DATIN （Lactam-DATIN） were included as disease controls. The clinicopathological characteristics and renal outcome at one year after renal biopsy were investigated and compared between the two groups. Results Compared to the Lactam-DATIN group, patients in the Herbal-DATIN group were of more female in gender （10/11 ）, less likely to present allergic symptoms, had longer duration of medication use and larger interval from starting taking medication to clinical onset The degree of inilamrnatory response and renal dysfunexion （serum creatinine） were similar between the two groups, but the levels of urinary N-acetyl-β-D-glucosaminidase （NAG） and microalbumin （mAlb） in Herbal-DATIN group were significantly lower than those in Lactam-DATIN group[NAG. 18 （12.5, 19.5） vs. 28 （14, 72.5）, P=0.05] mAlb.. 62.4 （47, 85.6） vs. 107 （76. 4, 172.5）, P = 0. 031 ]. There was no significant difference in the semi-quantitative scores of acute lesions in renal pathology between the two groups, whereas patients in Herbal-DATIN group had higher scores of tubular atrophy and interstitial fibrosis than those in Lactam-DATIN group [1.0 （0, 1.0） vs. 0 （0, 0）, P = 0. 033]. The eGFR levels in Herbal-DATIN group by one month and one year post-renal biopsy seemed to be lower than those in Lactam-DATIN group [one month： （40. 1 ± 19. 6 vs. 50.8 ±15.8ml·min·（1.73 m2）-1, P=0.207）; one year： （64.9±21.7 vs. 73.1±24.5 ml·min·（1.73 m2 ） - 1, p = 0. 448） ], whereas the difference did not reach statistical significance. Conclusions Herbal- DATIN is easily to be late diagnosed since the onset of the disease is most often insidious. More attention should be paid to patients on herbal medication and surveillance of kidney injury should be monitored during and after the treatment.