Plasma microRNA-192 expression as a potential biomarker of diabetic kidney disease in patients with type 2 diabetes mellitus
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Abstract
Background. Albuminuria is an early clinical indicator of diabetic kidney disease (DKD). However, it has several limitations. The aim of this study was to evaluate the plasma microRNA-192 (miRNA-192) expression and its diagnostic performance in patients with type 2 diabetes mellitus (T2DM) and DKD.
Methods. In this case-control study, 75 subjects were included into 3 groups: group (1): 20 patients with T2DM and UACR (urinary albumin creatinine ratio) < 30 mg/gm, group (2): 30 patients with T2DM and ACR ≥ 30 mg/gm, and group (3): 25 healthy controls. Patients were recruited from the outpatient clinic of the Diabetes unit at our institution. Real-Time Quantitative Reverse Transcription PCR was used to assess plasma miRNA-192 expression.
Results. Plasma miRNA-192 was significantly higher in T2DM patients with DKD compared to those with normal UAE. Additionally, in patients with T2DM, plasma miRNA-192 was positively correlated with UACR. The ROC curve analysis for miRNA-192 plasma expression in patients with T2DM, revealed that miRNA-192 had a good diagnostic performance (AUC = 0.778) to define T2DM patients with DKD.
Conclusion. Plasma expression of miRNA-192 was able to discriminate increased UAE among patients with T2DM; suggesting a promising role for miRNA-192 as a potential biomarker for DKD.
Keywords: ttype 2 diabetesdiabetic kidney diseasealbuminuriamicroRNAmicroRNA-192
References
- Saeedi P, Petersohn I, Salpea P, et al. IDF Diabetes Atlas Committee. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9 edition. Diabetes Res Clin Pract. 2019; 157: 107843.
- Tuttle KR, Bakris GL, Bilous RW, et al. Diabetic kidney disease: a report from an ADA Consensus Conference. Diabetes Care. 2014; 37(10): 2864–2883.
- Krolewski AS, Niewczas MA, Skupien J, et al. Early progressive renal decline precedes the onset of microalbuminuria and its progression to macroalbuminuria. Diabetes Care. 2014; 37(1): 226–234.
- MacIsaac RJ, Panagiotopoulos S, McNeil KJ, et al. Nonalbuminuric renal insufficiency in type 2 diabetes. Diabetes Care. 2004; 27(1): 195–200.
- Levey AS, Becker C, Inker LA. Glomerular filtration rate and albuminuria for detection and staging of acute and chronic kidney disease in adults: a systematic review. JAMA. 2015; 313(8): 837–846.
- Caramori ML, Kim Y, Huang C, et al. Cellular basis of diabetic nephropathy: 1. Study design and renal structural-functional relationships in patients with long-standing type 1 diabetes. Diabetes. 2002; 51(2): 506–513.
- Najafian B, Crosson JT, Kim Y, et al. Glomerulotubular junction abnormalities are associated with proteinuria in type 1 diabetes. J Am Soc Nephrol. 2006; 17(4 Suppl 2): S53–S60.
- Rossing P, Hougaard P, Parving HH. Progression of microalbuminuria in type 1 diabetes: ten-year prospective observational study. Kidney Int. 2005; 68(4): 1446–1450.
- Dave VP, Ngo TA, Pernestig AK, et al. MicroRNA amplification and detection technologies: opportunities and challenges for point of care diagnostics. Lab Invest. 2019; 99(4): 452–469.
- Mitchell PS, Parkin RK, Kroh EM, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008; 105(30): 10513–10518.
- Chen Xi, Ba Yi, Ma L, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008; 18(10): 997–1006.
- Guay C, Regazzi R. Circulating microRNAs as novel biomarkers for diabetes mellitus. Nat Rev Endocrinol. 2013; 9(9): 513–521.
- Ma X, Lu C, Lv C, et al. The Expression of miR-192 and Its Significance in Diabetic Nephropathy Patients with Different Urine Albumin Creatinine Ratio. J Diabetes Res. 2016; 2016: 6789402.
- American Diabetes Association, American Diabetes Association, American Diabetes Association. 2. Classification and Diagnosis of Diabetes: . Diabetes Care. 2019; 42(Suppl 1): S13–S28.
- American Diabetes Association. 11. Microvascular Complications and Foot Care: . Diabetes Care. 2019; 42(Suppl 1): S124–S138.
- Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care. 2004; 27(6): 1487–1495.
- Kantharidis P, Hagiwara S, Brennan E, et al. Study of microRNA in diabetic nephropathy: isolation, quantification and biological function. Nephrology (Carlton). 2015; 20(3): 132–139.
- Hu C, Sun L, Xiao L, et al. Insights into the Mechanisms Involved in the Expression and Regulation of Extracellular Matrix Proteins in Diabetic Nephropathy. Curr Med Chem. 2015; 22(24): 2858–2870.
- Sun Y, Koo S, White N, et al. Development of a micro-array to detect human and mouse microRNAs and characterization of expression in human organs. Nucleic Acids Res. 2004; 32(22): e188.
- Kato M, Zhang J, Wang M, et al. MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-beta-induced collagen expression via inhibition of E-box repressors. Proc Natl Acad Sci U S A. 2007; 104(9): 3432–3437.
- Kato M, Arce L, Wang M, et al. A microRNA circuit mediates transforming growth factor-β1 autoregulation in renal glomerular mesangial cells. Kidney Int. 2011; 80(4): 358–368.
- Putta S, Lanting L, Sun G, et al. Inhibiting microRNA-192 ameliorates renal fibrosis in diabetic nephropathy. J Am Soc Nephrol. 2012; 23(3): 458–469.
- Krupa A, Jenkins R, Luo DD, et al. Loss of MicroRNA-192 promotes fibrogenesis in diabetic nephropathy. J Am Soc Nephrol. 2010; 21(3): 438–447.
- Ruiz MA, Chakrabarti S. MicroRNAs: the underlying mediators of pathogenetic processes in vascular complications of diabetes. Can J Diabetes. 2013; 37(5): 339–344.
- Ahmed G, Saadi G, Meligi AEl, et al. Evaluation of microRNA-192 in patients with diabetic nephropathy. Egypt J Intern Med. 2019; 31(2): 122.
- Chien HY, Chen CY, Chiu YH, et al. Differential microRNA Profiles Predict Diabetic Nephropathy Progression in Taiwan. Int J Med Sci. 2016; 13(6): 457–465.
- Jia Y, Guan M, Zheng Z, et al. miRNAs in Urine Extracellular Vesicles as Predictors of Early-Stage Diabetic Nephropathy. J Diabetes Res. 2016; 2016: 7932765.
- Al-Kafaji G, Al-Muhtaresh HA. Expression of microRNA‑377 and microRNA‑192 and their potential as blood‑based biomarkers for early detection of type 2 diabetic nephropathy. Mol Med Rep. 2018; 18(1): 1171–1180.
- El-Monem A, Mahfouz M, Mohamed M. Microrna 192 Gene Expression in Type II Diabetic Nephropathy. The Egyptian Journal of Hospital Medicine. 2017; 68(1): 885–893.
- Houlihan CA, Tsalamandris C, Akdeniz A, et al. Albumin to creatinine ratio: a screening test with limitations. Am J Kidney Dis. 2002; 39(6): 1183–1189.
- Chudleigh RA, Dunseath G, Evans W, et al. How reliable is estimation of glomerular filtration rate at diagnosis of type 2 diabetes? Diabetes Care. 2007; 30(2): 300–305.