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糖尿病肾病中尿及肾脏足突细胞表面蛋白和足蛋白水平:一项肾脏活检研究

Urinary and Kidney Podocalyxin and Podocin Levels in Diabetic Kidney Disease: A Kidney Biopsy Study.

作者信息

Zeng Lingfeng, Fung Winston Wing-Shing, Chan Gordon Chun-Kau, Ng Jack Kit-Chung, Chow Kai-Ming, Szeto Cheuk-Chun

机构信息

Carol & Richard Yu Peritoneal Dialysis Research Centre, Department of Medicine & Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China.

Li Ka Shing Institute of Health Sciences (LiHS), Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.

出版信息

Kidney Med. 2022 Nov 14;5(1):100569. doi: 10.1016/j.xkme.2022.100569. eCollection 2023 Jan.

Abstract

RATIONALE & OBJECTIVE: Diabetic kidney diseases (DKDs) are the most common cause of dialysis-dependent kidney disease around the world. Previous studies have suggested that urinary level of podocyte-associated molecules may predict the prognosis of DKD.

STUDY DESIGN

Observational cohort.

SETTING & PARTICIPANTS: 118 consecutive patients with biopsy-proven DKD; 13 nondiabetic patients with hypertensive nephrosclerosis as controls.

PREDICTORS

Urinary podocalyxin and podocin levels were obtained by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) and the corresponding intrarenal levels by western blotting.

OUTCOMES

Dialysis-free survival; kidney event-free survival; rate of kidney function decline in 12 months.

ANALYTICAL APPROACH

Correlation and time to event analysis.

RESULTS

Urinary podocalyxin level was closely correlated with its messenger RNA (mRNA) level ( = 0.562,  < 0.001), but this did not predict the progression of DKD. Intrarenal podocalyxin level had only modest correlation with its urinary mRNA and ELISA levels, was an independent predictor of dialysis-free survival (adjusted HR, 1.85; 95% CI, 1.21-2.82;  = 0.005), and showed an insignificant trend of predicting kidney event-free survival (adjusted HR, 1.36; 95% CI, 0.94-1.95;  = 0.10). Urinary podocin level by ELISA had a modest correlation with the rate of kidney function decline ( = 0.238,  = 0.01) but did not predict dialysis-free survival.

LIMITATIONS

Small sample size; lack of serial measurement.

CONCLUSIONS

Intrarenal podocalyxin level, but not its urinary level, was an independent predictor of dialysis-free survival, whereas urinary podocin level by ELISA correlated with the rate of kidney function decline. Although intrarenal podocalyxin level has prognostic value, it may not be suitable for routine clinical use.

摘要

原理与目的

糖尿病肾病(DKD)是全球依赖透析的肾脏疾病最常见的病因。既往研究提示,足细胞相关分子的尿水平可能预测DKD的预后。

研究设计

观察性队列研究。

研究地点与参与者

118例经活检证实的DKD连续患者;13例非糖尿病性高血压肾硬化患者作为对照。

预测指标

通过定量聚合酶链反应和酶联免疫吸附测定(ELISA)获得尿足细胞标记蛋白和足蛋白水平,通过蛋白质印迹法获得相应的肾内水平。

观察指标

无透析生存期;无肾脏事件生存期;12个月内肾功能下降率。

分析方法

相关性分析和事件发生时间分析。

结果

尿足细胞标记蛋白水平与其信使核糖核酸(mRNA)水平密切相关(r = 0.562,P < 0.001),但这并不能预测DKD的进展。肾内足细胞标记蛋白水平与其尿mRNA和ELISA水平仅有中等程度的相关性,是无透析生存期的独立预测指标(校正风险比,1.85;95%可信区间,1.21 - 2.82;P = 0.005),且在预测无肾脏事件生存期方面显示出不显著的趋势(校正风险比,1.36;95%可信区间,0.94 - 1.95;P = 0.10)。ELISA法检测的尿足蛋白水平与肾功能下降率有中等程度的相关性(r = 0.238,P = 0.01),但不能预测无透析生存期。

局限性

样本量小;缺乏系列测量。

结论

肾内足细胞标记蛋白水平而非其尿水平是无透析生存期的独立预测指标,而ELISA法检测的尿足蛋白水平与肾功能下降率相关。虽然肾内足细胞标记蛋白水平具有预后价值,但可能不适合常规临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e14/9841354/9aea60ef057f/fx1.jpg

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