Szeto Cheuk-Chun, Ng Jack Kit-Chung, Fung Winston Wing-Shing, Luk Cathy Choi-Wan, Wang Gang, Chow Kai-Ming, Lai Ka-Bik, Li Philip Kam-Tao, Lai Fernand Mac-Moune
Department of Medicine & Therapeutics, Prince of Wales Hospital, Hong Kong, China.
Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
Kidney Med. 2020 Dec 4;3(1):76-82.e1. doi: 10.1016/j.xkme.2020.11.009. eCollection 2021 Jan-Feb.
RATIONALE & OBJECTIVE: Previous studies have suggested that microRNA-21 (miR-21) plays an important role in kidney fibrosis. We examined the relationship between intrarenal miR-21 level and rate of kidney function loss in immunoglobulin A nephropathy (IgAN).
Prospective cohort study.
SETTING & PARTICIPANTS: 40 patients with IgAN and 10 with hypertensive nephrosclerosis as controls.
miR-21 levels in kidney biopsy specimen and urinary sediment, quantified as ratio to the housekeeping gene.
Kidney event-free survival and rate of kidney function decline.
Time-to-event and correlation analysis.
The IgAN group had significantly higher intrarenal miR-21 expression compared with the hypertensive nephrosclerosis group (1.71 [IQR, 0.99-2.77] vs 0.31 [IQR, 0.25-1.32]; < 0.0001), but urinary miR-21 levels were similar. Intrarenal miR-21 expression had significant but modest correlation with severity of glomerulosclerosis ( = 0.293; = 0.05) and tubulointerstitial fibrosis ( = 0.341; = 0.03). Patients with high intrarenal miR-21 expression had significantly higher risk for developing kidney end points compared with those with low expression (log-rank test, = 0.017). Univariate Cox analysis showed that intrarenal miR-21 expression significantly predicted the development of kidney end points (unadjusted HR, 1.586; 95% CI, 1.179-2.134; = 0.002). However, the result was just short of statistical significance after adjusting for the severity of histologic damage ( = 0.06). There was also a significant correlation between intrarenal miR-21 expression and the slope of kidney function decline by univariate analysis ( = -0.399; = 0.02).
Small sample size; uncertain cellular origin of miR-21.
We found that intrarenal miR-21 expression is increased in patients with IgAN, modestly correlated with the severity of histologic damage, and predictive of subsequent kidney function loss.
既往研究表明，微小RNA-21（miR-21）在肾纤维化中起重要作用。我们研究了免疫球蛋白A肾病（IgAN）患者肾内miR-21水平与肾功能丧失率之间的关系。
前瞻性队列研究。
40例IgAN患者和10例高血压性肾硬化患者作为对照。
肾活检标本和尿沉渣中miR-21水平，以与管家基因的比值进行定量。
无肾脏事件生存期和肾功能下降率。
事件发生时间分析和相关性分析。
与高血压性肾硬化组相比，IgAN组肾内miR-21表达显著更高（1.71[四分位间距，0.99 - 2.77]对0.31[四分位间距，0.25 - 1.32]；P < 0.0001），但尿miR-21水平相似。肾内miR-21表达与肾小球硬化严重程度（r = 0.293；P = 0.05）和肾小管间质纤维化（r = 0.341；P = 0.03）显著但中度相关。肾内miR-21高表达患者发生肾脏终点事件的风险显著高于低表达患者（对数秩检验，P = 0.017）。单因素Cox分析显示，肾内miR-21表达显著预测肾脏终点事件的发生（未调整的风险比，1.586；95%置信区间，1.179 - 2.134；P = 0.002）。然而，在调整组织学损伤严重程度后，结果仅接近统计学显著性（P = 0.06）。单因素分析还显示肾内miR-21表达与肾功能下降斜率显著相关（r = -0.399；P = 0.02）。
样本量小；miR-21的细胞来源不确定。
我们发现IgAN患者肾内miR-21表达增加，与组织学损伤严重程度中度相关，并可预测随后的肾功能丧失。
