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Review
. 2022 Jul 28:11:21.
doi: 10.12703/r/11-21. eCollection 2022.

AKI-to-CKD transition is a potential mechanism for non-albuminuric diabetic kidney disease

Kyung Lee  1 , John Cijiang He  1   2
Affiliations
Review

AKI-to-CKD transition is a potential mechanism for non-albuminuric diabetic kidney disease

Kyung Lee et al. Fac Rev. .

Abstract

Although albuminuria development is considered the natural course of diabetic kidney disease (DKD), increasing evidence indicate that the disease can present as non-albuminuric DKD (NA-DKD), characterized by prominent tubulointerstitial injury and fibrosis without obvious glomerulopathy. However, the pathogenic mechanisms underlying NA-DKD remain unclear. As diabetic patients are more susceptible to acute kidney injury (AKI), and the maladaptive repair of kidney tubules following AKI occurs more frequently in diabetic than non-diabetic patients, the enhanced AKI-to-CKD transition may be a significant contributor of NA-DKD. Recent studies indicate that endoplasmic reticulum (ER) stress is a key pathogenic driver of AKI-to-CKD transition, and that the tubular expression of ER-resident protein reticulon 1A (RTN1A) correlates with human DKD progression and AKI-to-CKD transition. Experimental studies showed that RTN1A indeed mediates tubular cell injury and AKI-to-CKD transition in diabetic mice via concomitant activation of ER stress and mitochondrial dysfunction as a mediator of ER-mitochondrial crosstalk. Further understanding of the pathogenesis of tubular injury in DKD will help us to develop sensitive and specific biomarkers or diagnostic tools to distinguish between injury-related AKI, pre-renal AKI from hemodynamic changes, and the progression of DKD in order to better manage patients with DKD.

Keywords: RTN1A; acute kidney injury; albuminuria; chronic kidney disease; diabetic kidney disease; endoplasmic reticulum; mitochondria; renal tubular epithelial cells.

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Conflict of interest statement

The authors declare that they have no competing interests.No competing interests were disclosed.No competing interests were disclosed.

Figures

Figure 1.
Figure 1.. RTN1A injury kidney cells via activation of ER-mitochondrial contact.
RTN1A-HK1 interaction disrupts HK1-VDAC1 interaction, thereby releasing VDAC1 to induce inflammasome- and BCL2-mediated apoptosis. EMC, endoplasmic reticulum-mitochondrial contact; ER, endoplasmic reticulum; HK1, hexokinase-1; RTN1A, reticulon 1A; VDAC, voltage-dependent anion channel.
See this image and copyright information in PMC

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