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Citation
Tags
HERO ID
6775018
Reference Type
Journal Article
Subtype
Review
Title
The proximal tubule is the primary target of injury and progression of kidney disease: role of the glomerulotubular junction
Author(s)
Chevalier, RL
Year
2016
Is Peer Reviewed?
Yes
Journal
American Journal of Physiology: Renal Physiology
ISSN:
1931-857X
Volume
311
Issue
1
Page Numbers
F145-F161
Language
English
PMID
27194714
DOI
10.1152/ajprenal.00164.2016
Web of Science Id
WOS:000380826900019
Abstract
There is an alarming global increase in the incidence of end-stage kidney disease, for which early biomarkers and effective treatment options are lacking. Largely based on the histology of the end-stage kidney and on the model of unilateral ureteral obstruction, current investigation is focused on the pathogenesis of renal interstitial fibrosis as a central mechanism in the progression of chronic kidney disease (CKD). It is now recognized that cumulative episodes of acute kidney injury (AKI) can lead to CKD, and, conversely, CKD is a risk factor for AKI. Based on recent and historic studies, this review shifts attention from the glomerulus and interstitium to the proximal tubule as the primary sensor and effector in the progression of CKD as well as AKI. Packed with mitochondria and dependent on oxidative phosphorylation, the proximal tubule is particularly vulnerable to injury (obstructive, ischemic, hypoxic, oxidative, metabolic), resulting in cell death and ultimately in the formation of atubular glomeruli. Animal models of human glomerular and tubular disorders have provided evidence for a broad repertoire of morphological and functional responses of the proximal tubule, revealing processes of degeneration and repair that may lead to new therapeutic strategies. Most promising are studies that encompass the entire life cycle from fetus to senescence, recognizing epigenetic factors. The application of techniques in molecular characterization of tubule segments and the development of human kidney organoids may provide new insights into the mammalian kidney subjected to stress or injury, leading to biomarkers of early CKD and new therapies.
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