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尿环孢素 A 和血清胱抑素 C 作为 1 型糖尿病儿童糖尿病肾病的生物标志物。

Urinary Cyclophilin A and serum Cystatin C as biomarkers for diabetic nephropathy in children with type 1 diabetes.

机构信息

Faculty of Medicine, Department of Pediatrics, Pediatric Endocrinology and Diabetes Unit, Mansoura University, Mansoura, Egypt.

Faculty of Medicine, Department of Clinical Pathology, Mansoura University, Mansoura, Egypt.

出版信息

Pediatr Diabetes. 2020 Aug;21(5):846-855. doi: 10.1111/pedi.13019. Epub 2020 Apr 28.

DOI:10.1111/pedi.13019
PMID:32304131
Abstract

BACKGROUND

Currently, microalbuminuria is the gold standard for detection and prediction of diabetic nephropathy (DN). However, microalbuminuria appears once significant kidney damage has actually occurred.

OBJECTIVES

We investigated the diagnostic role of urinary Cyclophilin-A (uCypA), uCypA/creatinine ratio (uCypA/Cr) and serum Cystatin-C (sCysC) as biomarkers for early detection of DN in children with type 1 diabetes mellitus (T1DM) of short duration (2-5 years) before microalbuminuria emerges.

METHODS

uCypA, uCypA/Cr, and sCysC levels were assessed in three age- and sex-matched groups; microalbuminuric diabetic group (n = 31), normoalbuminuric diabetic group (n = 29), and control group (n = 30). Glomerular filtration rate was estimated (eGFR) based on both serum creatinine (eGFR-Cr) and sCysC (eGFR-CysC).

RESULTS

Significantly higher sCysC and lower eGFR-CysC were detected in both diabetic groups compared to controls and in microalbuminuric compared to normoalbuminuric group. No detected significant difference in eGFR-Cr values across the studied groups. Both uCypA and uCypA/Cr were significantly elevated in microalbuminuric compared to both normoalbuminuric and control groups with no difference between normoalbuminuric and control groups. Prediction of microalbuminuria was conducted using sCysC with area under curve up to 0.980. Combined use of sCysC and uCypA had better diagnostic value than uCypA alone.

CONCLUSION

sCysC is a promising early biomarker for DN in childhood T1DM before albuminuria detection. eGFR-CysC is superior to eGFR-Cr in evaluating renal status in childhood T1DM. uCypA and uCypA/Cr were useful tools in predicting microalbuminuria, although not regarded as diagnostic biomarkers for early-stage DN in T1DM children by the current study.

摘要

背景

目前,微量白蛋白尿是检测和预测糖尿病肾病(DN)的金标准。然而,微量白蛋白尿仅在肾脏已经发生显著损伤后才会出现。

目的

我们旨在研究尿环孢素 A(uCypA)、uCypA/肌酐比值(uCypA/Cr)和血清胱抑素 C(sCysC)作为生物标志物在儿童 1 型糖尿病(T1DM)中用于在微量白蛋白尿出现之前早期检测糖尿病肾病的诊断作用,这些儿童的病程较短(2-5 年)。

方法

评估了三组年龄和性别匹配的患者的 uCypA、uCypA/Cr 和 sCysC 水平,包括微量白蛋白尿糖尿病组(n=31)、正常白蛋白尿糖尿病组(n=29)和对照组(n=30)。基于血清肌酐(eGFR-Cr)和 sCysC(eGFR-CysC)估计肾小球滤过率(eGFR)。

结果

与对照组相比,两个糖尿病组的 sCysC 显著升高,eGFR-CysC 显著降低,且微量白蛋白尿组比正常白蛋白尿组升高更显著。各组间 eGFR-Cr 值无显著差异。微量白蛋白尿组的 uCypA 和 uCypA/Cr 均显著高于正常白蛋白尿组和对照组,且正常白蛋白尿组和对照组之间无差异。使用 sCysC 进行微量白蛋白尿预测的曲线下面积高达 0.980。与单独使用 uCypA 相比,sCysC 与 uCypA 联合使用具有更好的诊断价值。

结论

sCysC 是儿童 T1DM 发生微量白蛋白尿之前的一种有前途的早期糖尿病肾病生物标志物。eGFR-CysC 优于 eGFR-Cr 用于评估儿童 T1DM 的肾脏状态。uCypA 和 uCypA/Cr 是预测微量白蛋白尿的有用工具,但本研究未将其视为 T1DM 儿童早期糖尿病肾病的诊断性生物标志物。

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