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Abstract: TH-PO248

Transcriptome Analysis of Human Kidney Tissues to Explore Prognostic Factors in Diabetic Kidney Disease With Nodular Lesion

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Imasawa, Toshiyuki, National Hospital Organization Chiba-Higashi National Hospital, Chiba, Japan
  • Unoki-Kubota, Hiroyuki, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan
  • Hirano, Daishi, Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan
  • Kaburagi, Yasushi, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan
Background

The prognosis of diabetic kidney disease (DKD) with nodular lesion (NL) is poor. However, there are cases in which the prognosis is not poor even in the presence of NL. The mechanism of why these patients do not have a poor prognosis remains unclear.

Methods

Twelve patients with a histological diagnosis of DKD with NL and no other renal comorbidities who had undergone kidney biopsy within the past 10 years and had been followed up for at least 3 years at a single institution with a uniform treatment strategy were included. Total RNA was extracted from renal biopsy tissues in formalin-fixed paraffin-embedded blocks and gene expression profile of the kidney was analyzed using microarray. The good prognosis (GP) group was defined as patients with an annual eGFR decline rate of < 5 ml/min/1.73 m2.

Results

The eGFR, urinary protein, and rate of sclerotic glomeruli at the time of renal biopsy in the poor prognosis (PP; n=6) and GP groups (n=6) were 47±18 and 45±15 mL/min/1.73 m2, 7.5±4.2 and 4.0±2.7 g/gCre, and 19±13% and 26±14%, respectively, none of which differed between the two groups. In the microarray analysis, genes with little or no expression (raw signals <50 and |processed signals| <0.3) were excluded and then 14227 genes were used for the analyses. A total of 1496 differentially expressed genes (DEGs) were selected by the criteria of P-values < 0.05 and |fold change| ≥ 2. Using the Ingenuity Pathway Analysis system, 15 canonical pathways and 9 diseases or functions annotations were found to be enriched. In addition, 73 upstream regulators were enriched, including CCN5 which was predicated to be significantly activated in the GP group. Moreover, one regulatory effect and 25 networks were revealed to be associated with the DEGs. The associated regulatory effect was ‘viral infection’ in which CCN5 is predicted to regulate the expression of CDH1, CD24, and ESR1 genes. The top five networks with a score of > 30 contained ESR1, extracellular signal-regulated kinase, and AKT which were predicted to be activated in the GP group.

Conclusion

Some factors identified in the present study have been reported to be as renoprotective factors in the past, which imply that they function to prevent the progression of DKD with NL.

Funding

  • Government Support – Non-U.S.