Kidney Week

Abstract: TH-PO549

Spatial Transcriptomic Profiling of Glomeruli in FSGS and Minimal Change Disease That Appear Normal on Light Microscopy

Session Information

• Glomerular Diseases: Omics, Biomarkers, and Tools
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Kim, Hyung Woo, Yonsei University College of Medicine, Seoul, Korea (the Republic of)

Hyung Woo Kim, MD

• Jung, Minsun, Yonsei University College of Medicine, Seoul, Korea (the Republic of)

Minsun Jung, MD, PhD

• Lee, Chung, Yonsei University College of Medicine, Seoul, Korea (the Republic of)

Chung Lee, PhD

• Heo, Ga Young, Yonsei University College of Medicine, Seoul, Korea (the Republic of)

Ga Young Heo, MD

• Park, Cheol Ho, Yonsei University College of Medicine, Seoul, Korea (the Republic of)

Cheol Ho Park, MD, PhD

• Yun, Hae-Ryong, Yonsei University College of Medicine, Seoul, Korea (the Republic of)

Hae-Ryong Yun, MD, PhD

• Park, Jung Tak, Yonsei University College of Medicine, Seoul, Korea (the Republic of)

Jung Tak Park, MD, PhD

• Yoo, Tae-Hyun, Yonsei University College of Medicine, Seoul, Korea (the Republic of)

Tae-Hyun Yoo, MD, PhD

• Kang, Shin-Wook, Yonsei University College of Medicine, Seoul, Korea (the Republic of)

Shin-Wook Kang, MD, PhD

• Lim, Beom Jin, Yonsei University College of Medicine, Seoul, Korea (the Republic of)

Beom Jin Lim, MD, PhD

• Han, Seung Hyeok, Yonsei University College of Medicine, Seoul, Korea (the Republic of)

Seung Hyeok Han, MD, PhD

Background

Distinguishing between minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) based solely on pathological findings is challenging, with no validated biomarkers available for their discrimination.

Methods

Using the GeoMx Digital Spatial Profiler, spatial transcriptomic profiling was performed on formalin-fixed paraffin-embedded kidney biopsy specimens from five patients with MCD and three patients with FSGS (one tip variant and two NOS variants), all of whom presented with nephrotic syndrome. Additionally, we included four control patients from time zero biopsy of kidney recipients. Glomerular regions of interest were selected and outlined by two kidney pathologists using the web interface. For FSGS, glomeruli with and without sclerosis were selected separately. Differential gene expression (DEGs) analyses were conducted by fitting each gene’s Q3 normalized expression level using edgeR. Gene ontology (GO) enrichment analyses of DEGs were performed using clusterProfiler.

Results

After excluding genes exhibiting expression levels below 5% of the ROIs in each sample, a final analysis was conducted on the remaining gene expression levels of 13,929 genes. Compared with glomeruli from MCD, normal glomeruli from FSGS exhibited increased expression of GPR141, and DEFB104A and decreased expression of BRD2, FAM124A, and MYADM. Sclerotic glomeruli from FSGS showed increased expression of WIPI1 and CLCN7 and decreased expression of PODXL, NDNF, DCN, and HTRA1 compared with glomeruli from MCD. When comparing normal and sclerotic glomeruli from FSGS, normal glomeruli showed increased expression of NPHS2, COL4A3, ID1, and ADAMTSL5, whereas sclerotic glomeruli showed increased expression of RPS23, RPL27A, EEF1G, and CRTAP. Additionally, GO analyses revealed significant enrichment of genes for genes related to various biologic processes when these three phenotypes were compared with each other.

Conclusion

Utilizing digital spatial profiling identified significant differences in the expression profiles between glomeruli in FSGS and MCD that appear normal on light microscopy. Future studies are warranted to validate our findings and evaluate whether the observed genes could serve as discriminative biomarkers between the two phenotypes.