Differential microRNA Profiles Predict Diabetic Nephropathy Progression in Taiwan.
OBJECTIVE
Diabetic nephropathy (DN) is a major leading cause of kidney failure. Recent studies showed that serological microRNAs (miRs) could be utilized as biomarkers to identify disease pathogenesis; the DN-related miRs, however, remained to be explored.


METHODS
A prospective case-control study was conducted. The clinical significance of five potential miRs (miR-21, miR-29a, miR-29b, miR-29c and miR192) in type 2 Diabetes Mellitus (T2DM) patients who have existing diabetic retinopathy with differential Albumin:Creatinine Ratio (ACR) and estimated Glomerular Filtration Rate (eGFR) was performed using quantitative RT-PCR analysis. The subjects with diabetic retinopathy enrolled in Taipei City Hospital, Taiwan, were classified into groups of normal albuminuria (ACR<30mg/g; N=12); microalbuminuria (30mg/g<ACR<300mg/g; N=17) and overt proteinuria (ACR>300mg/g; N=21) as well as 18 low-eGFR (eGFR<60ml/min) and 32 high-eGFR (eGFR>60ml/min). The level of serum miRs was statistically correlated with age, Glucose AC, ACR, eGFR and DN progression.


RESULTS
The levels of miR-21, miR-29a and miR-192 were significantly enriched in the overt proteinuria group compared with microalbuminuria and/or overt proteinuria groups. It was shown that only miR-21 level was significantly up-regulated in low-eGFR group compared with high-eGFR patients. Interestingly, Pearson's correlation coefficient analysis demonstrated that DN progressors showed significantly greater levels of miR-21, miR-29a, miR-29b and miR-29c in comparison with non-progressors implying the clinical potential of DN associated miRs in monitoring and preventing disease advancement.


CONCLUSIONS
Our findings showed that miR-21, miR-29a/b/c and miR-192 could reflect DN pathogenesis and serve as biomarkers during DN progression.
1. Department of Endocrinology & Metabolism, Taipei City Hospital, Ren-Ai Branch, Taipei, Taiwan;
Hung-Yu
HY
Chien
2. Institute of Oral Biology and Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan;
Chang-Yi
CY
Chen
3. Department of Education and Research, Taipei City Hospital, Taipei, Taiwan;
Yen-Hui
YH
Chiu
4. Division of Endocrinology &Metabolism, Taipei Veterans General Hospital, Taipei, Taiwan;; 5. Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan;
Yi-Chun
YC
Lin
2. Institute of Oral Biology and Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan;; 3. Department of Education and Research, Taipei City Hospital, Taipei, Taiwan;
Wan-Chun
WC
Li
D000419:Albuminuria / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics; D003928:Diabetic Nephropathies / Q000097:blood / Q000235:genetics*; D018450:Disease Progression; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D011446:Prospective Studies; D012307:Risk Factors; D013624:Taiwan
D015415:Biomarkers; C524940:MIRN21 microRNA, human; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D003404:Creatinine
Albumin:creatinine ratio; Biomarkers; Circulating microRNA; Diabetic nephropathy; Estimated Glomerular Filtration Rate.