Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India.
Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India.
Int Urol Nephrol. 2023 Jun;55(6):1557-1564. doi: 10.1007/s11255-023-03464-w. Epub 2023 Jan 17.
IgA nephropathy (IgAN), the most common primary glomerulonephritis, often presents as advanced renal failure with end-stage renal disease at diagnosis. Tubulointerstitial injury and fibrosis on histology are the most important predictors of renal outcome. A non-invasive biomarker is required for assessment of progression in IgA nephropathy. We investigated the utility of blood profibrotic molecules, TGF-β1 and miRNA-21-5p (miR-21), to identify a non-invasive biomarker for renal fibrosis in IgAN.
The study included 30 IgAN (mean age 31.5 ± 9 years) at the time of initial diagnosis, 25 age-sex-matched healthy controls and 10 Lupus nephritis patients as disease controls. Serum TGF-β1 was analyzed by enzyme-linked immunosorbent assay and plasma miR-21 by qRT-PCR, normalized with U6-snRNA. The levels were correlated with clinical features, laboratory parameters, histological Oxford MEST-C score and renal outcome.
The serum TGF-β1 and plasma miR-21 were significantly higher in patients with IgAN than in healthy controls. TGF-β1 significantly correlated with serum creatinine, eGFR, Oxford T score and miR-21. High plasma miR-21 was significantly associated with T score and interstitial inflammation. On multivariate analysis, high levels of TGF-β1 and miR-21 correlated with lower eGFR and T score, respectively. On a follow-up period of 21.5 months, high miR-21 expression at diagnosis was associated (p = 0.02) with a poor renal outcome having a shorter time to doubling of serum creatinine.
High blood TGF-β1 and miR-21 expression at diagnosis of IgAN show significant correlation with renal function and degree of chronic tubulointerstitial injury on histology.
IgA 肾病（IgAN）是最常见的原发性肾小球肾炎，常以诊断时的终末期肾病为表现出现进行性肾衰竭。组织学上的肾小管间质损伤和纤维化是肾脏结局的最重要预测指标。需要一种非侵入性的生物标志物来评估 IgA 肾病的进展。我们研究了血液促纤维化分子 TGF-β1 和 miRNA-21-5p（miR-21）在识别 IgAN 肾纤维化非侵入性生物标志物方面的效用。
该研究纳入了 30 名初诊时的 IgAN 患者（平均年龄 31.5±9 岁）、25 名年龄和性别匹配的健康对照者和 10 名狼疮肾炎患者作为疾病对照者。采用酶联免疫吸附试验分析血清 TGF-β1，采用 qRT-PCR 分析血浆 miR-21，以 U6-snRNA 为内参进行标准化。将这些水平与临床特征、实验室参数、组织学牛津 MEST-C 评分和肾脏结局进行相关性分析。
IgAN 患者的血清 TGF-β1 和血浆 miR-21 显著高于健康对照组。TGF-β1 与血清肌酐、eGFR、牛津 T 评分和 miR-21 显著相关。高血浆 miR-21 与 T 评分和间质炎症显著相关。多变量分析显示，高水平的 TGF-β1 和 miR-21 分别与较低的 eGFR 和 T 评分相关。在 21.5 个月的随访期间，初诊时高 miR-21 表达与较差的肾脏结局相关（p=0.02），即血清肌酐加倍的时间较短。
IgAN 初诊时的高血 TGF-β1 和 miR-21 表达与肾功能和组织学上慢性肾小管间质损伤的程度显著相关。
