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CKD 患者尿沉渣和上清液足细胞生物标志物的排泄模式。

Excretion Patterns of Urinary Sediment and Supernatant Podocyte Biomarkers in Patients with CKD.

机构信息

Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Yufu, Japan.

Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.

出版信息

Kidney360. 2021 Nov 5;3(1):63-73. doi: 10.34067/KID.0004772021. eCollection 2022 Jan 27.

Abstract

BACKGROUND

Podocyte depletion causes glomerulosclerosis, and persistent podocyte loss drives progression to ESKD. Urinary sediment podocin (u-sed Pod) mRNA excretion and urinary supernatant podocalyxin (u-sup PCX) protein have been used to monitor disease activity in glomerular diseases. However, the differences in these markers among pathologies have not been investigated. We examined the roles of these markers in kidney diseases.

METHODS

From January 2013 to March 2016, early morning urine samples were collected from 12 healthy controls and 172 patients with kidney disease (=15 patients with minor glomerular abnormality with mild proteinuria and/or microscopic hematuria, =15 with minimal change nephrotic syndrome [MCNS], =15 with membranous nephropathy [MN], =60 with IgA nephropathy [IgAN], =19 with crescentic GN [Cres GN], =10 with lupus nephritis [LN], and =38 with other kidney diseases). We examined u-sed Pod mRNA excretion, u-sup PCX protein, and the urinary protein-creatinine ratio (u-PCR).

RESULTS

u-sed Pod mRNA excretion was significantly correlated with u-sup PCX protein (=0.37, <0.001). Both u-sed Pod mRNA excretion and u-sup PCX protein were significantly correlated with u-PCR (=0.53, <0.001 and =0.35, <0.001, respectively). Interestingly, u-sed Pod mRNA excretion was significantly increased in proliferative-type GN-including IgAN with extracapillary proliferative lesions, Cres GN, and LN class IV-and significantly correlated with the rate of crescent formation, whereas u-sup PCX protein was significantly increased only in those with MN and subepithelial dense deposit-type LN compared with controls.

CONCLUSIONS

Higher u-sed Pod mRNA excretion and u-sup PCX protein were associated with proliferative-type GN, indicating podocyte detachment and subepithelial dense deposit-type GN, respectively. The results suggest that u-sed Pod mRNA excretion and u-sup PCX protein have usefulness for the diagnosis and measurement of disease activity with regard to glomerular diseases.

摘要

背景

足细胞耗竭会导致肾小球硬化,而持续的足细胞丢失会导致 ESKD 的进展。尿沉渣 podocin(u-sed Pod)mRNA 排泄和尿上清液 podocalyxin(u-sup PCX)蛋白已被用于监测肾小球疾病的疾病活动。然而,这些标志物在不同病理中的差异尚未被研究。我们研究了这些标志物在肾脏疾病中的作用。

方法

从 2013 年 1 月至 2016 年 3 月,收集了 12 名健康对照者和 172 名肾病患者的晨尿样本(=15 名肾小球轻度异常伴轻度蛋白尿和/或镜下血尿患者,=15 名微小病变性肾病综合征[MCNS]患者,=15 名膜性肾病[MN]患者,=60 名 IgA 肾病[IgAN]患者,=19 名新月体性肾小球肾炎[Cres GN]患者,=10 名狼疮性肾炎[LN]患者,=38 名其他肾病患者)。我们检测了尿沉渣 podocin(u-sed Pod)mRNA 排泄、尿上清液 podocalyxin(u-sup PCX)蛋白和尿蛋白/肌酐比值(u-PCR)。

结果

尿沉渣 podocin(u-sed Pod)mRNA 排泄与尿上清液 podocalyxin(u-sup PCX)蛋白显著相关(r=0.37,<0.001)。尿沉渣 podocin(u-sed Pod)mRNA 排泄和尿上清液 podocalyxin(u-sup PCX)蛋白均与 u-PCR 显著相关(r=0.53,<0.001 和 r=0.35,<0.001)。有趣的是,尿沉渣 podocin(u-sed Pod)mRNA 排泄在增生性 GN 中显著增加,包括伴有毛细血管外增生病变的 IgAN、Cres GN 和 LN Ⅳ型,且与新月体形成率显著相关,而尿上清液 podocalyxin(u-sup PCX)蛋白仅在 MN 和上皮下密沉积型 LN 患者中与对照组相比显著增加。

结论

尿沉渣 podocin(u-sed Pod)mRNA 排泄和尿上清液 podocalyxin(u-sup PCX)蛋白的增加与增生性 GN 相关,提示足细胞脱落和上皮下密沉积型 GN。结果表明,尿沉渣 podocin(u-sed Pod)mRNA 排泄和尿上清液 podocalyxin(u-sup PCX)蛋白对肾小球疾病的诊断和疾病活动的测量具有一定的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/085f/8967611/41fc3a749ea9/KID.0004772021absf1.jpg

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