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Review
. 2017 Dec;30(6):701-717.
doi: 10.1007/s40620-017-0423-9. Epub 2017 Aug 24.

A more tubulocentric view of diabetic kidney disease

Letizia Zeni  1   2   3 , Anthony G W Norden  4 , Giovanni Cancarini  5   6 , Robert J Unwin  4   7
Affiliations
Review

A more tubulocentric view of diabetic kidney disease

Letizia Zeni et al. J Nephrol. 2017 Dec.

Abstract

Diabetic nephropathy (DN) is a common complication of Diabetes Mellitus (DM) Types 1 and 2, and prevention of end stage renal disease (ESRD) remains a major challenge. Despite its high prevalence, the pathogenesis of DN is still controversial. Initial glomerular disease manifested by hyperfiltration and loss of glomerular size and charge permselectivity may initiate a cascade of injuries, including tubulo-interstitial disease. Clinically, 'microalbuminuria' is still accepted as an early biomarker of glomerular damage, despite mounting evidence that its predictive value for DN is questionable, and findings that suggest the proximal tubule is an important link in the development of DN. The concept of 'diabetic tubulopathy' has emerged from recent studies, and its causative role in DN is supported by clinical and experimental evidence, as well as plausible pathogenetic mechanisms. This review explores the 'tubulocentric' view of DN. The recent finding that inhibition of proximal tubule (PT) glucose transport (via SGLT2) is nephro-protective in diabetic patients is discussed in relation to the tubule's potential role in DN. Studies with a tubulocentric view of DN have stimulated alternative clinical approaches to the early detection of diabetic kidney disease. There are tubular biomarkers considered as direct indicators of injury of the proximal tubule (PT), such as N-acetyl-β-D-glucosaminidase, Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1, and other functional PT biomarkers, such as Urine free Retinol-Binding Protein 4 and Cystatin C, which reflect impaired reabsorption of filtered proteins. The clinical application of these measurements to diabetic patients will be reviewed in the context of the need for better biomarkers for early DN.

Keywords: Diabetic kidney disease; Diabetic tubulopathy; Hyperfiltration; Microalbuminuria; SGLT2 nephro-protection; Tubular biomakers.

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Conflict of interest statement

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors.

Figures

Fig. 1
Fig. 1
Interactions between glomerulus and proximal tubule (PT) in the pathophysiology of microalbuminuria, hyperfiltration and proximal tubule glucose (GLU) reabsorption in the context of DKD
Fig. 2
Fig. 2
Classification of urinary biomarkers in diabetic kidney disease [–66]. *Tubular biomarker further discussed in the text
Fig. 3
Fig. 3
Proteomics and MicroRNAs approach to DKD
See this image and copyright information in PMC

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