# Capturing the inflammatory landscape within kidney compartments of human diabetic kidney disease: a digital spatial profiling study

## TL;DR

This study uses digital spatial profiling to map immune cell markers in diabetic kidney disease, revealing inflammatory patterns that could improve treatment approaches.

## Contribution

The novel use of NanoString GeoMx™ Digital Spatial Profiling to quantitatively analyze immune cell markers in specific kidney compartments of DKD patients.

## Key findings

- Inflammatory cell surface markers like CD4, CD68, and CD40 are elevated in DKD tubules and interstitium compared to normal tissue.
- CD163, a prorepair macrophage marker, is increased in DKD tubules and interstitium compared to normal tissue.
- CD34 levels are lower in DKD tubules and interstitium compared to normal but higher in DKD than in TIN.

## Abstract

To quantitatively examine immune cell markers and spatial distribution in human diabetic kidney disease (DKD) to enhance understanding of the inflammatory landscape contributing to injury. Maladaptive inflammation is an underrecognized contributor to DKD pathogenesis and progression and remains undertreated.

NanoString GeoMx™ Digital Spatial Profiling technology targeted antibodies labeled with unique oligonucleotide barcode in kidney biopsy [DKD (n=5), tubulointerstitial nephritis (TIN; n=4), and normal (n=2)] with regions of interest selection of compartments (glomeruli, tubules, interstitium). Inflammation-related proteins were analyzed with differential expression through linear mixed modeling.

Compared to normal tissue, inflammatory cell surface protein markers were increased in DKD tubules and interstitium. Markers of T cells (CD4, CD44), macrophages (CD68; proinflammatory), and antigen-presenting cells (APCs; CD40 and CD11c) were increased across all DKD compartments (vs. normal). Macrophage (CD163; prorepair) marker was increased in DKD tubules and interstitium (vs. normal). Fewer differences were observed in glomeruli for normal vs. DKD or TIN vs. DKD groups. CD66b+ (granulocytes) cell marker was higher in DKD (vs. TIN). As expected, TIN had higher levels of T cell and macrophage markers in tubules and interstitium (vs. DKD). Interestingly, CD34, a hematopoietic stem cell and endothelial cell marker, was lower in DKD tubules and interstitium (vs. normal) but higher in DKD (vs. TIN).

NanoString GeoMx DSP technology may fulfil a role in enhancing the understanding the inflammatory landscape engaged in DKD pathogenesis as well as measuring response to therapy. Moreover, additional investigations of CD34 progenitor cell depletion in DKD may be warranted.