Background: Studies suggested that eosinophils in diabetes might be associated with severity of diabetic nephropathy (DN). In a retrospective study of 102 Chinese patients with biopsy-proven DN, we aimed to evaluate relationships of both blood and renal eosinophils (Eos) to the severity of DN and check whether Eos can serve as an indicator of prognosis as well as the therapeutic effect of steroids.
Methods: One hundred and two patients diagnosed with DN were enrolled. Demographical and clinical data and histopathological scores were associated. Interstitial eosinophilic aggregates (IEA) were defined as the presence of ≥10 Eos in at least one high-power field. End-stage renal disease was defined as the end point.
Results: We observed that log2 (blood eosinophil counts) correlated with neutrophil counts, proteinuria, and tubulointerstitial inflammatory cell infiltration. IEA was observed in 33.3% of the DN patients and was associated with decreased estimated glomerular filtration rate, higher proteinuria, hematuria, higher HbA1c, increased blood eosinophil counts, tubular injury, tubulointerstitial chronicity, and interstitial inflammation. IEA was associated with worse renal prognosis (hazard ratio [HR] 2.424, P = 0.008). Consistently, urine eosinophil cationic protein (ECP) (ng/mgCr) was associated with renal injury and poor renal prognosis (HR 1.173, P = 0.020). Patients with IEA were more likely to be treated with steroid/immunosuppressants (47.1% vs 14.7%, P = 0.001) but did not show renal benefit.
Conclusions: It suggested that both blood and renal infiltrated eosinophils were prevalent in DN and associated with severity of DN. IEA in renal pathology showed better fit in correlation with renal prognosis. Treatment with steroid/immunosuppressants showed no significant improvement regarding renal prognosis.
背景: 已有研究表明糖尿病中的嗜酸性粒细胞(eosinophil, Eos)可能与糖尿病肾病(diabetic nephropathy, DN)的严重程度有关。在本项由102例肾活检病理诊断为DN患者的回顾性研究中, 我们旨在探究血液和肾间质中的Eos与DN严重程度的相关性, 以及Eos是否可以作为判断预后及类固醇治疗效果的指标。 方法: 本研究共纳入102例DN患者, 收集分析其临床病理指标。肾间质嗜酸性粒细胞聚集灶(interstitial eosinophilic aggregates, IEA)定义为至少一个高倍视野下出现≥10个Eos。终末期肾脏病定义为终点。 结果: 我们观察到log2 (血液嗜酸性粒细胞计数)与中性粒细胞计数、蛋白尿和肾小管间质炎症细胞浸润相关。在33.3%的糖尿病肾病患者中观察到间质性膀胱炎, 其与肾小球滤过率降低、蛋白尿、血尿、HbA1c升高、血嗜酸性粒细胞计数增加、肾小管损伤、肾小管间质慢性化和间质性炎症相关。IEA与肾脏预后差有关(危险比[HR] 2.424, P = 0.008)。并且, DN患者尿嗜酸粒细胞阳离子蛋白(eosinophil cationic protein, ECP)(ng/mgCr)水平与肾脏预后不良相关(HR 1.173, p=0.020)。与不存在IEA的DN患者相比较, 存在IEA的DN患者中使用糖皮质激素/免疫抑制剂治疗的比例更高(47.1% vs. 14.7%, p=0.001), 但使用糖皮质激素/免疫抑制剂治疗的IEA患者与未使用的IEA患者相比, 肾功能未见改善。 结论: DN患者血液和肾脏浸润性嗜酸性粒细胞普遍存在, 并与DN的严重程度相关。肾间质存在IEA的DN患者肾损伤的临床病理均较重, 肾脏预后较差。存在IEA的DN患者应用糖皮质激素/免疫抑制剂治疗未能观察到明确的治疗效果。.
Keywords: diabetic nephropathy; eosinophil; pathology; prognosis; steroid; 嗜酸性粒细胞; 病理; 糖尿病肾病; 糖皮质激素; 预后.
© 2020 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.