Potential for Novel Biomarkers in Diabetes-Associated Chronic Kidney Disease: Epigenome, Metabolome, and Gut Microbiome

Abstract

Diabetes-associated chronic kidney disease is a pandemic issue. Despite the global increase in the number of individuals with this chronic condition together with increasing morbidity and mortality, there are currently only limited therapeutic options to slow disease progression. One of the reasons for this is that the current-day “gold standard” biomarkers lack adequate sensitivity and specificity to detect early diabetic chronic kidney disease (CKD). This review focuses on the rapidly evolving areas of epigenetics, metabolomics, and the gut microbiome as potential sources of novel biomarkers in diabetes-associated CKD and discusses their relevance to clinical practice. However, it also highlights the problems associated with many studies within these three areas—namely, the lack of adequately powered longitudinal studies, and the lack of reproducibility of results which impede biomarker development and clinical validation in this complex and susceptible population.

High-Throughput Metabolomics and Diabetic Kidney Disease Progression: Evidence from the Chronic Renal Insufficiency (CRIC) Study

“…Metabolites, low-weight intermediates and end products of cellular pathways, could uncover physiological or pathological changes in chronic diseases [7]. Recent research emphasizes the importance of and need for further research on the human urine metabolome in kidney disease [8,9]. Previous urine metabolome in DKD studies has largely been cross-sectional and aimed at identifying metabolites distinguishing DKD from healthy or suitable comparison controls [10][11][12].…”

“…Metabolites, low-weight intermediates and end products of cellular pathways, could uncover physiological or pathological changes in chronic diseases [7]. Recent research emphasizes the importance of and need for further research on the human urine metabolome in kidney disease [8, 9].…”

Genome-wide Analysis Reflects Novel 5-Hydroxymethylcytosines Implicated in Diabetic Nephropathy

“…Notably, conventional clinical markers to evaluate renal functions of DN, including serum creatinine, estimated glomerular filtration rate (eGFR), and urinary albumin, can be influenced by many factors. (3) Pathologically, the “gold standard” to diagnose DN has been percutaneous renal biopsy. However, various complications can be caused by the procedure, such as bleeding, pain, and infection.…”

“…(5) Particularly, epigenetic modifications are gene regulatory elements that sit between phenotypes and genotypes. (3) To date, the most-investigated epigenetic modification is DNA methylation, i.e., 5-methylcytosines (5mC), which has been implicated in various normal and pathogenesis processes. The regulation of DNA methylation in vivo is a dynamic process.…”

Epigenomic signatures in age-related macular degeneration: Focus on their role as disease modifiers and therapeutic targets

“…Intriguingly, epigenetic factors have been found to be associated with susceptibility and progression from early to advanced stages of several diseases, including chronic kidney disease, diabetes, cancers, immune/inflammatory disorders. [5][6][7][8] Among these disorders, Age-related Macular Degeneration (AMD) represents one of the most common eye disorder affecting elderly individuals, 9 causing legal blindness in 1.8 millions of individuals worldwide. 10 The prevalence has been estimated equal to 7.3% in Asian population and to 12.3% in European and American populations.…”