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Abstract: TH-PO242

Assessing the Inflammatory Landscape of Human Diabetic Kidney Disease (DKD) Through NanoString Digital Spatial Profiling Technology

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical


  • Elhusseiny, Khaled Mosaad, Mayo Clinic in Florida, Jacksonville, Florida, United States
  • Cornell, Lynn D., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Bian, Xiaohui, Mayo Clinic in Florida, Jacksonville, Florida, United States
  • Ma, Yaohua, Mayo Clinic in Florida, Jacksonville, Florida, United States
  • Hickson, LaTonya J., Mayo Clinic in Florida, Jacksonville, Florida, United States

Group or Team Name

  • Mayo Translational and Regenerative Nephrology Research Laboratory

Inflammation contributes to DKD pathogenesis and progression. We examined the inflammatory signature of kidney biopsy tissue from subjects with DKD compared to those with normal histology and tubulointerstitial nephritis (TIN)


Core needle biopsy samples were stained with a fluor-labeled antibodies against pan-cytokeratin (epithelium), CD45 (T-cell), and CD68 (macrophage) plus the nuclear dye (STYO13). It also contained 77 target antibodies, each labeled with a unique oligonucleotide barcode. Regions of interest (ROI) were selected based on kidney compartments, and two segments were collected from each ROI: cytokeratin-positive = tubule, cytokeratin-negative/STYO13-positive = interstitium. Antibody-bound oligonucleotides were liberated by UV laser irradiation of computer-defined masks to collect oligonucleotides and then quantified using nCounter technology. Data were normalized to the geometric mean of three housekeeping proteins (GAPDH, histone H3, S6). Differential expression was assessed using the linear mixed model


Surface protein expression of inflammatory cells (Figure: red, yellow) were increased in the tubules and interstitium of DKD (n=5) and TIN kidney (n=4) compared to normal (n=2) patients. Infiltration of interstitial CD68+ macrophages were higher in DKD vs. normal, yet lower vs. TIN (P < 0.05). Similarly, CD45+ and CD8+ T-cells were significantly increased in DKD vs. normal tubulointerstitium but decreased vs. TIN. While, CD66b+ granulocytes were higher in DKD tubulointerstitium (vs. normal), it did not show significant difference between DKD and TIN


The inflammatory landscape of DKD is characterized by tubulointerstitial infiltration of macrophages, T-cells and granulocytes which is not as robust as TIN but significantly higher than normal healthy kidney tissue. Hence, targeting pro-inflammatory pathway in DKD may represent an important therapeutic targeting for DKD


  • NIDDK Support