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Abstract: PO0980

Investigations on Urinary mRNA Biomarkers That Reflect Pathologic Features of Patients with Diabetic Kidney Diseases

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Lee, Yu ho, CHA Bundang Medical Center, Seongnam, Gyeonggi-do, Korea (the Republic of)
  • Jung-Woo, Seo, Kyung Hee University, Seoul, Korea (the Republic of)
  • Kim, Miji, Kyung Hee University, Seoul, Korea (the Republic of)
  • Jeong, Hye yun, CHA Bundang Medical Center, Seongnam, Gyeonggi-do, Korea (the Republic of)
  • Lee, So-young, CHA Bundang Medical Center, Seongnam, Gyeonggi-do, Korea (the Republic of)
  • Kim, Yang gyun, Kyung Hee University, Seoul, Korea (the Republic of)
  • Lee, Sangho, Kyung Hee University, Seoul, Korea (the Republic of)
  • Kim, Jin sug, Kyung Hee University, Seoul, Korea (the Republic of)
  • Hwang, Hyeon Seok, Kyung Hee University, Seoul, Korea (the Republic of)
  • Jeong, Kyung hwan, Kyung Hee University, Seoul, Korea (the Republic of)
  • Moon, Ju young, Kyung Hee University, Seoul, Korea (the Republic of)
Background

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease worldwide. Despite that histological severity of DKD is a well-established predictor of adverse renal outcomes, investigations on the identification of non-invasive biomarkers that can reflect intrarenal status are scarce. The purpose of this study was to discover urinary mRNA biomarkers of DKD and to examine their associations with the degree of various pathologic features.

Methods

We collected and analyzed urinary samples obtained from 68 patients with biopsy-proven DKD and 32 healthy controls. Using two public GEO dataset (GPL22945 and GPL24120), we compared renal transcriptomic profiles of DKD and healthy living kidney donors and selected candidate genes for DKD (|fold change| > 2 and p < 0.001, compared to controls). The levels of selected candidate genes were measured by quantitative real-time polymerase chain reaction using urine cell pellet.

Results

Mean estimated glomerular filtration rate and urinary protein-to-creatinine ratio of enrolled patients were 45.5 mL/min/1.73 m2 and 7.4 g/g creatinine, respectively. A total of 30 candidate genes were selected based on the analysis of GEO dataset, among which 22 genes were significantly elevated in urines of patients with DKD compared to controls. In particular, urinary col1a1 levels were significantly higher in patients with advanced glomerular pathologic scores, while urinary cx3cr1 and sox4 levels were significantly lower in these patients. The expression of urinary cx3cr1 levels was also lower in patients with more severe IFTA. On the other hand, urinary pdk4 levels showed positive correlation with its scores. Urinary c3 and nnmt levels were positively correlated with the severity of interstitial inflammation and arterial hyalinosis, respectively. Finally, we found significant correlation between the amount of urinary protein-to-creatinine ratio and urinary levels of nnmt, thbs2, plk2, and cola1a1.

Conclusion

Urinary mRNAs could reflect the degree of intrarenal pathologic status in patients with diabetic kidney disease.

Funding

  • Government Support - Non-U.S.