Uromodulin mRNA from Urinary Extracellular Vesicles Correlate to Kidney Function Decline in Type 2 Diabetes Mellitus
| Autor: | Robert R. Henry, Taku Murakami, Masato Mitsuhashi, Melanie Oakes, Colleen Kelly, Cindy Yamamoto, Kumar Sharma |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Tamm–Horsfall protein Urinary system 030232 urology & nephrology Renal function Type 2 diabetes Kidney Risk Assessment Severity of Illness Index 03 medical and health sciences Extracellular Vesicles 0302 clinical medicine Predictive Value of Tests Internal medicine Diabetes mellitus Uromodulin medicine Humans Diabetic Nephropathies Obesity RNA Messenger Renal Insufficiency Chronic Aged biology business.industry Type 2 Diabetes Mellitus Middle Aged medicine.disease Prognosis Healthy Volunteers 030104 developmental biology Endocrinology Real-time polymerase chain reaction Diabetes Mellitus Type 2 ROC Curve Nephrology biology.protein Female business Cell-Free Nucleic Acids Biomarkers Kidney disease Glomerular Filtration Rate |
| Zdroj: | American journal of nephrology. 47(5) |
| ISSN: | 1421-9670 |
| Popis: | Background: Extracellular vesicles (EVs) enclose mRNA derived from their cell of origin and are considered a source of potential biomarkers. We examined urinary EV mRNA from individuals with diabetic kidney disease (DKD), chronic kidney disease, type 2 diabetes (T2DM), and obese and healthy controls to determine if such biomarkers had the potential to classify kidney disease and predict patients at higher risk of renal function decline. Methods: A total of 242 participants enrolled in this study. Urinary EV mRNA from all subjects were isolated by a filter-based platform, and the expression of 8 target genes were determined by quantitative polymerase chain reaction (qPCR). Changes in estimated glomerular filtration rate (eGFR) in 161 T2DM patients were evaluated for 2 consecutive years and compared with EV RNA profiles at baseline. Results: We observe that mild and severe DKD groups show a significant 3.2- and 4.4-fold increase in UMOD compared to healthy controls and expression increases linearly from healthy, diabetic, and DKD subjects. UMOD expression is significantly correlated to albumin creatinine ratio (ACR), eGFR, and HbA1c. Using linear discriminant analyses with mRNA from severe DKD and T2DM as training data, a multi-gene signature classified DKD and non-DKD with a sensitivity of 93% and specificity of 73% with area under the receiver operating characteristic (ROC) curve (AUC) = 0.90. Although 6% of T2DM were determined to have a > 80% posterior probability of developing DKD based on this mRNA profile, eGFR changes observed within the 2-year follow-up did not reveal a decline in kidney function. Conclusion: Urinary EV UMOD mRNA levels are progressively elevated from T2DM to DKD groups and correlate with widely used eGFR and ACR diagnostic criteria. An EV mRNA signature could identify DKD with greater than 90% sensitivity and 70% specificity. |
| Databáze: | OpenAIRE |
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