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Abstract: TH-PO1045

Exosomal Micro RNA as a Diagnostic Tool in Kidney Biopsy Cohort

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Yoshida, Teruhiko, NIDDK, National Institutes of Health, Bethesda, United States
  • Hamasaki, Yoshifumi, University of Tokyo, Tokyo, Japan
  • Miyamoto, Yoshihisa, the University of Tokyo Hospital, Tokyo, Japan
  • Komaru, Yohei, the University of Tokyo Hospital, Tokyo, Japan
  • Doi, Kent, University of Tokyo, Tokyo, Japan
  • Kopp, Jeffrey B., NIDDK, National Institutes of Health, Bethesda, Maryland, United States
  • Nangaku, Masaomi, the University of Tokyo School of Medicine, Tokyo, Japan
Background

Despite recent advances, clinical renal diagnosis requires pathological examination of a kidney biopsy. Micro RNAs (miRNAs) in exosomes are promising biomarkers for kidney disease diagnosis and management. We sought to identify diagnostic miRNAs in exosomes from blood and urine obtained from subjects with diabetic nephropathy.

Methods

We performed a prospective single-center cohort study, enrolling patients who underwent kidney biopsy at the University of Tokyo Hospital. Blood and urine samples and clinical parameters were obtained at the time of the kidney biopsy. Exosomes were isolated from blood and urine by ultracentrifugation and RNA was extracted. We selected candidate miRNAs by TaqMan array card and measured expression by quantitative PCR. The outcome variable was standardized pathological diagnosis. We confirmed the principal findings by experiments in streptozotocin (STZ)-induced diabetic mice.

Results

The study population consisted of 102 patients who underwent kidney biopsy, including 8 with diabetic nephropathy and 23 with diabetes who had other kidney diseases. For the diagnosis of diabetic nephropathy, a clinical model (diabetic history, retinopathy and hematuria) had moderate accuracy, with AUC [95% CI] 0.65 [0.44-0.81]. Urinary exosomal miR-486 added significant accuracy when combined with the clinical model, showing AUC 0.92 [0.76-0.98] (p=0.003). In STZ diabetic mice, miR-486 expression was reduced by 94% in urinary exosomes (p=0.003) and by 40% in laser capture micro-dissected glomeruli (p=0.02) compared with non-diabetic mice.

Conclusion

Levels of miRNAs in urinary exosomes correlated with the histological diagnosis of diabetic nephropathy and may be a promising non-invasive diagnostic tool.

Receiver operating characteristic (ROC) curves for diagnosis of human diabetic nephropathy

Funding

  • NIDDK Support