Diabetes Metab J.  2022 Mar;46(2):181-197. 10.4093/dmj.2021.0329.

Pathophysiologic Mechanisms and Potential Biomarkers in Diabetic Kidney Disease

• Jung CY
• Yoo TH

• KMID: 2527714
• DOI: http://doi.org/10.4093/dmj.2021.0329

Abstract

Although diabetic kidney disease (DKD) remains the leading cause of end-stage kidney disease eventually requiring chronic kidney replacement therapy, the prevalence of DKD has failed to decline over the past 30 years. In order to reduce disease prevalence, extensive research has been ongoing to improve prediction of DKD onset and progression. Although the most commonly used markers of DKD are albuminuria and estimated glomerular filtration rate, their limitations have encouraged researchers to search for novel biomarkers that could improve risk stratification. Considering that DKD is a complex disease process that involves several pathophysiologic mechanisms such as hyperglycemia induced inflammation, oxidative stress, tubular damage, eventually leading to kidney damage and fibrosis, many novel biomarkers that capture one specific mechanism of the disease have been developed. Moreover, the increasing use of high-throughput omic approaches to analyze biological samples that include proteomics, metabolomics, and transcriptomics has emerged as a strong tool in biomarker discovery. This review will first describe recent advances in the understanding of the pathophysiology of DKD, and second, describe the current clinical biomarkers for DKD, as well as the current status of multiple potential novel biomarkers with respect to protein biomarkers, proteomics, metabolomics, and transcriptomics.

Keyword

Biomarkers; Diabetic nephropathies; Inflammation; Metabolomics; Oxidative stress; Pathophysiology; Proteomics; Transcriptome

Figure

• 

  Fig. 1. The pathophysiology of potential and novel biomarkers of diabetic kidney disease classified by their target pathophysiological pathways. AGE, advanced glycation end products; PKC, protein kinase C; IGF-1, insulin like growth factor-1; EGF, epidermal growth factor; PDGF, platelet-derived growth factor; VEGF, vascular endothelial growth factor; TGF-β, transforming growth factor-β; Ang II, angiotensin II; TNF-α, tissue necrosis factor-α; INF-γ, interferon-γ; IL-1, interleukin-1; IL-6, interleukin-6; Nlrp3, nod-like receptor protein-3; ROS, reactive oxygen species; CCL2, C-C motif chemokine 2; ICAM-1, intracellular adhesion molecule 1; TNFR1, tissue necrosis factor receptor 1; TNFR2, tissue necrosis factor receptor 2; PAI-1, plasminogen activator inhibitor-1; VCAM-1, vascular cell adhesion protein-1; CRP, C-reactive protein; Nrf2, nuclear factor erythroid 2-related factor; NOS, nitric oxide synthase; 8-OHdG, 8-Hydroxy-2’-deoxyguanosine.

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