New Biomarkers for Diabetic Kidney Disease to Improve Diagnosis and Monitoring

Diabetic kidney disease (DKD) is a major microvascular complication arising from type 2 diabetes mellitus (T2DM), leading to end-stage renal disease (ESRD). Despite advancements in treatment options such as hyperglycemic and blood pressure control and renin-angiotensin system blockades, DKD continues to prevail at alarming rates. Clinically, DKD often progresses from microalbuminuria to macroalbuminuria, marked by increased levels of albumin in the urine and an initial hyperfiltration phase followed by a gradual decline in renal function. However, variations in clinical presentations and progression rates to ESRD have been noted in recent studies. As scientific understanding evolves, the need for specific biomarkers for DKD has become increasingly vital. Now, an analysis of urinary and exosome proteome profiling by a team of scientists has led to the discovery of biomarkers for DKD, offering the potential for early diagnosis and treatment.

The research carried out by scientists at the Chinese Academy of Sciences (Beijing, China) involved extensive urinary proteomics analysis of 144 patients and urinary exosome proteomics of 44 patients with varying degrees of albuminuria related to T2DM. Utilizing exosomes for biomarker discovery offers several benefits, including minimizing the presence of abundant proteins in urine and enriching a subproteome comprising membrane and cytosolic proteins. Urinary exosomes also provide crucial information from a wide range of epithelial origins, reflecting physiological or pathological processes in virtually all epithelial cells exposed to the urinary space. Additionally, proteomic analysis of urinary exosomes can identify proteins specifically linked to certain kidney diseases, as was the case in this study.

The study analyzed urine samples from 144 clinical patients, including 19 healthy controls and 125 DM patients. The diabetic group was further categorized into three stages based on albumin-to-creatinine ratio (ACR) values. The research highlighted the dynamic nature of urinary and exosome proteomes in T2DM patients at different albuminuria stages. Proteins were grouped into six clusters based on their expression patterns throughout DKD progression. The study observed a significant decrease in proteins associated with glycolytic and ubiquitination processes from healthy controls to early DM stages, with a gradual decrease continuing to the late DM stages. Conversely, proteins involved in lipid transport and cholesterol esterification progressively increased, peaking at the most advanced stage. Proteins involved in carbohydrate metabolic processes showed high expression in early DM patients, decreasing as DKD progressed. Additionally, the study identified and validated potential biomarkers for DKD diagnosis or disease monitoring, such as SERPINA1 and TF, in another cohort of diabetic urine samples with varying DKD degrees. Thus, this research has provided a deeper understanding of the biomarkers associated with renal disease, fueling hopes for improved early-stage treatments and management strategies for DKD.

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Chinese Academy of Sciences