Case Control Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Nov 26, 2019; 7(22): 3698-3710
Published online Nov 26, 2019. doi: 10.12998/wjcc.v7.i22.3698
Human podocyte injury in the early course of hypertensive renal injury
Da Sun, Jiao-Jiao Wang, Wei Wang, Juan Wang, Li-Ning Wang, Li Yao, Ying-Hui Sun, Zi-Long Li
Da Sun, Jiao-Jiao Wang, Wei Wang, Juan Wang, Li-Ning Wang, Li Yao, Zi-Long Li, Department of Nephrology, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
Ying-Hui Sun, Department of Experimental Medicine, General Hospital of Northern Theater Command, Shenyang 110016, Liaoning Province, China
Author contributions: Sun YH and Li ZL conceived the study; Sun D, Wang JJ, Wang W and Wang J collected the clinical data and biological specimens and performed the research; Wang LN and Yao L analyzed the data; Sun D and Li ZL drafted the manuscript; all authors approved the final version of the article.
Supported by the Natural Science Foundation of Liaoning Provincial Department of Science and Technology, No. 2017225020.
Institutional review board statement: The study was approved by Clinical Institutional Review Board for Human Research (Ethics Committee) of China Medical University.
Informed consent statement: Written informed consent was obtained from all participants prior to enrollment in the study.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at yinghui_sun@163.com. Participants gave informed consent for data sharing.
STROBE statement: The guidelines of the STROBE Statement have been adopted.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Ying-Hui Sun, MD, Associate Chief Physician, Department of Experimental Medicine, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenhe District, Shenyang 110016, Liaoning Province, China. yinghui_sun@163.com
Telephone: +86-24-28851712
Received: September 8, 2019
Peer-review started: September 8, 2019
First decision: October 24, 2019
Revised: November 3, 2019
Accepted: November 15, 2019
Article in press: November 15, 2019
Published online: November 26, 2019
ARTICLE HIGHLIGHTS
Research background

Emerging evidence has shown that podocyte injury contributes to the development of renal damage associated with hypertensive kidney injury; however, the mechanism remains unclear and human data are limited.

Research motivation

This study aimed to investigate human podocyte injury induced by hypertension in the early course without massive proteinuria or decreased renal function. Based on the information obtained in this study, it is expected to provide novel diagnostic methods and therapeutic strategies for hypertensive renal injury in the future.

Research objectives

In this study, we summarized the method for detecting urinary podocytes, excluded the interference of physiological shedding, and verified the evaluation significance of urinary podocytes for hypertensive renal injury in the clinic. In addition, we preliminarily investigated the molecular mechanism of podocyte injury in the early course of hypertensive renal injury.

Research methods

Human urine specimens and kidney tissue were used in this study. Urinary podocytes were observed under light microscopy and confocal microscopy. The intrarenal expression of podocyte-specific proteins, nephrin and CD2-associated protein (CD2AP) were detected by immunohistochemical techniques under different hemodynamic conditions and quantified by integral optical density values. The ultrastructure of human glomeruli was examined using transmission electron microscopy.

Research results

Nucleated cells expressing nephrin or CD2AP were defined to be podocytes, and were detected in urine sediment in the hypertension group. By contrast, few podocytes were observed in control group 1. Moreover, podocyte foot process fusion and significantly decreased nephrin and/or CD2AP expression in glomeruli were observed in the hypertension group compared with control group 2, indicating podocyte injury and detachment from glomerular basement membrane, which was consistent with urinary detection of podocytes.

Research conclusions

Decreased expression and the abnormal redistribution of neprhin and CD2AP are causally related to the disruption of podocyte morphology, and together with urinary podocytes lost from the glomerulus, confirm that podocyte injury is a key event in the progression of hypertensive kidney injury. Furthermore, podocyturia appears early in the course of hypertensive renal injury, and may be a sensitive marker for early prediction of hypertensive renal injury.

Research perspectives

Calcium channels, associated signaling pathways and downstream cytokines are closely related to the regulatory mechanisms of podocytes, which is the research focus of hypertensive renal injury in future studies.