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Abstract: PO1662

EGR1 Is an Injury Marker in Podocytes

Session Information

Category: Glomerular Diseases

  • 1204 Podocyte Biology

Authors

  • Okabe, Masahiro, Jikei University School of Medicine, Tokyo, Japan
  • Tsuboi, Nobuo, Jikei University School of Medicine, Tokyo, Japan
  • Matsusaka, Taiji, Tokai University School of Medicine, Isehara, Japan
  • Yokoo, Takashi, Jikei University School of Medicine, Tokyo, Japan
Background

There is no good marker that depicts injured podocytes in human histology samples as well as desmin staining in rodent samples. EGR1 (Early Growth Response 1) is a transcriptional factor that regulates cell survival, proliferation, and cell death in response to growth factors, DNA damage, and ischemia. We have reported that injured podocytes express EGR1 protein in the early stages of damage in animal experiments and that EGR1 is expressed on podocytes in human glomeruli. This study aims to explore an association between EGR1 staining in podocytes and podocyte injury in human glomerular diseases.

Methods

Patients who underwent kidney biopsy at Jikei University Hospital, Tokyo, from June 2018 to March 2020 were recruited. Exclusion criteria included age < 20 years, glomeruli < 8, tubulointerstitial diseases, and kidney transplant patients. Blood and urine were collected during the kidney biopsy, and estimated glomerular filtration rate (eGFR), urinary protein to creatinine ratio (UPCR), urinary nephrin mRNA, and urinary podocin mRNA were measured. From the kidney biopsy specimen, the percentage of glomeruli with podocytes expressing EGR1 (%EGR1), the percentage of sclerotic glomeruli (%GS), and the glomerular podocin expression scores were measured. The %EGR1 was compared with these parameters using Spearman’s rank correlation coefficient.

Results

Ninety-eight patients were included in this study (male, 58%; median age, 49 [interquartile range, 36–60] years; eGFR, 65 [44–79] mL/min/1.73m2, UPCR, 0.90 [0.43–2.46] g/g; %EGR1, 26.1 [14.6–41.4]%; IgA nephropathy, n=35; hypertensive nephrosclerosis, n=10; membranous nephropathy, n=6; lupus nephropathy, n=5; minimal change disease (MCD), n=5; and focal segmental nephrosclerosis (FSGS), n=3). The %EGR1 was correlated with UPCR, urinary nephrin mRNA, urinary podocin mRNA, and glomerular podocin expression scores (rho=0.303, 0.378, 0.369, and -0.286; and P=0.0024, <0.001, <0.001, and 0.0043, respectively) but not with eGFR and %GS. In the subgroup with IgA nephropathy, %EGR1 was also correlated with UPCR and urinary podocin mRNA (rho=0.413 and 0.378; and P=0.014 and 0.025, respectively). Interestingly, the %EGR1 was low in MCD (8.33 [0.0–15.4]%), and high in FSGS (40.0 [36.8–46.3]%).

Conclusion

EGR1 expression in podocytes is associated with podocyte injury. EGR1 could be a podocyte injury marker in human glomeruli.

Funding

  • Government Support – Non-U.S.