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Abstract: SA-PO236

Alterations of the Kidney Inflammatory Landscape in Patients With Diabetic Nephropathy

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Chirra, Martina, University of Cincinnati, Cincinnati, Ohio, United States
  • Chimote, Ameet A., University of Cincinnati, Cincinnati, Ohio, United States
  • Dahal, Arya, University of Cincinnati, Cincinnati, Ohio, United States
  • Bhati, Sonia, University of Cincinnati, Cincinnati, Ohio, United States
  • Duncan, Heather, University of Cincinnati, Cincinnati, Ohio, United States
  • Kant, Kotagal Shashi, University of Cincinnati, Cincinnati, Ohio, United States
  • Conforti, Laura, University of Cincinnati, Cincinnati, Ohio, United States
Background

Diabetic nephropathy (DN) is the leading cause of chronic kidney disease in the USA. Inflammation has a crucial role in the pathogenesis of DN and a deeper knowledge of the inflammatory state of DN kidneys could provide rationales for new treatments. Our aim was to investigate the transcriptomic immune signature of kidney biopsies from patients with DN, in comparison with healthy kidney (NK) biopsies and kidney biopsies of patients affected by lupus nephritis (LN), a well-known example of immune-related kidney disease.

Methods

We performed a transcriptomic analysis of formalin-fixed paraffin-embedded kidney biopsies from NK (n=7), DN (n=7) and LN (n=4) using the NanoString nCounter MAX system and the nCounter Human Autoimmune Profiling Panel. Gene expression and pathway score data analyses were performed with the nSolver 4.0 Data Analysis Software, the Advanced Analysis 2.0 plug-in (NanoString Technologies) and the ROSALIND® platform. All the LN patients were receiving immunosuppressant drugs during the sample collection.

Results

31% (239/750) of the genes defining autoimmune and autoinflammatory disorders were upregulated (fold increase ≥ 1.5, adjusted P-value ≤ 0.05) in DN compared to NK. When comparing DN with LN, there were 159 differentially expressed genes (fold increase ≥ 1.5 or fold decrease ≤ 1.5, adjusted P-value ≤ 0.05) and 140/159 were upregulated in DN compared to LN. Almost all the pathways (34/35) associated with autoimmune and chronic inflammatory disorders were significantly increased in DN (n=5) compared to NK (n=7). The majority of these pathways (19/35) were still increased in DN (n=2) compared to LN (n=4).

Conclusion

Transcriptional profiling of DN kidney biopsies reveals an increase of the pathways associated with autoimmune and chronic inflammatory disorders, potentially identifying new therapeutic targets.

Funding

  • Other NIH Support