Kidney Week

Abstract: TH-PO753

Podocyte Injury Marker EGR1 in Lupus Nephritis

Session Information

• Glomerular Diseases: Podocyte Biology - I
  November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1403 Podocyte Biology

Authors

• Okabe, Masahiro, Jikei University School of Medicine, Tokyo, Japan

Masahiro Okabe,

• Koike, Kentaro, Jikei University School of Medicine, Tokyo, Japan

Kentaro Koike,

• Tsuboi, Nobuo, Jikei University School of Medicine, Tokyo, Japan

Nobuo Tsuboi,

• Matsusaka, Taiji, Tokai University School of Medicine, Isehara, Japan

Taiji Matsusaka,

• Yokoo, Takashi, Jikei University School of Medicine, Tokyo, Japan

Takashi Yokoo,

Background

We have discovered that early growth response 1 (EGR1) is expressed in injured podocytes from an early stage in animal studies. Additionally, we have observed that EGR1 expression in podocytes correlates with proteinuria, urinary nephrin/podocin mRNA levels, and glomerular podocin expression in patients with glomerular diseases. These findings suggest that EGR1 could potentially serve as a marker of podocyte injury. The objective of this study is to investigate the relationship between EGR1 expression in podocytes and the activity of lupus nephritis (LN).

Methods

We recruited patients diagnosed with LN by kidney biopsy at Jikei University Hospital, Tokyo, between January 2001 and March 2020. Patients under 20 years and those with fewer than 8 glomeruli were excluded. We collected the SLE disease activity index (SLEDAI), estimated glomerular filtration rate (eGFR), and urinary protein excretion (UPE) levels from the patients’ medical records during kidney biopsy. We measured the percentages of glomeruli with podocytes expressing EGR1 (%EGR1glo), sclerotic glomeruli (%GS), glomeruli with endocapillary hypercellularity (%Endo), and glomeruli with cellular/fibrocellular crescents (%Cres), as well as tubulointerstitial damage from the kidney biopsy specimens. %EGR1glo was compared with these parameters using Spearman’s rank correlation coefficient, and %EGR1glo between LN classes was compared using the Kruskal-Wallis test. Multiple comparison corrections were conducted using Holm-Bonferroni method.

Results

Seventy-five patients were included in this study (84% female, median age 38 [interquartile range 31–50] years, SLEDAI 17 [14–22], eGFR 86 [60–103] mL/min/1.73 m², UPE level 1.49 [0.57–3.23] g/d, and %EGR1glo 14.3 [8.8–28.6]%). LN classes were 4% Class I, 8% Class II, 44% Class III, 36% Class IV, and 8% Class V. %EGR1glo showed correlations with SLEDAI, eGFR and UPE level (rho = 0.419, -0.358, and 0.45; P = 0.003, 0.018, and <0.001, respectively). In the histological analysis, %EGR1 was significantly higher in Class IV than in the other classes (vs Class I + II, P <0.001; vs Class III, P <0.001: and vs Class V, P = 0.004). %EGR1glo correlated with %Endo and %Cres (rho = 0.566 and 0.586; P <0.001 and <0.001, respectively), but not with %GS or tubulointerstitial damage.

Conclusion

EGR1 expression in podocytes was associated with the activity of LN, especially with acute lesions.

Funding

• Government Support – Non-U.S.