Abstract: SA-PO563
Extent of Glomerular Filtrate Determines the Pattern of Podocyte Detachment
Session Information
- Glomerular Diseases: Fibrosis, Extracellular Matrix
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix
Authors
- Saga, Nobuyuki, University of Tsukuba, Tsukuba, IBARAKI, Japan
- Matsusaka, Taiji, Tokai University School of Medicine, Isehara, KANAGAWA, Japan
- Nagata, Michio, University of Tsukuba, Tsukuba, IBARAKI, Japan
Background
Podocyte detachment is a hallmark of segmental glomerulosclerosis. In ASN Kidney Week 2018, we presented that the cell detachment occurred locally and dominantly at the side of urinary pole even in diffuse cell injury in NEP25 mouse. In addition, by adding unilateral ureter obstruction (UUO) in the mouse model, we showed that glomerular filtrate was essential for detachment. In the present study, we focused on the effects of hyperfiltration to the changes of detachment pattern in diffuse podocyte injury model.
Methods
We used NEP25 mouse, a model of podocyte-specific injury by immunotoxin (LMB2) injection. We performed UUO at 5 days or uninephrectomy (UNx) at 1 day after LMB2 injection. Whole glomerular profiles were photographed by TEM from LMB2+UUO contralateral kidney (61 glomeruli, n=3) and LMB2+UNx model (65 glomeruli, n=3) and compared with the data from LMB2 model (47 glomeruli, n=4). Entire GBM in all glomeruli were classified into normal, foot process effacement or detachment and each length per glomerulus was measured. This method enabled us to identify the localization, continuity and relationship of each change. The relationships between the depth of the glomerulus and the severity of detachment were also analyzed in all models.
Results
The average lengths of detachment were significantly longer in both LMB2+UUO contralateral kidney (12.27%) and LMB2+UNx model (14.21%) than in LMB2 model (5.20%). The tendency of detachment to occur near the urinary pole was enhanced in LMB2+UUO contralateral kidney. By contrast, detachment occurred globally without the tendency in LMB2+UNx model. Detachment was most severe not at the deepest area (750-1000 um) but at 500-750 um from the surface in all models. In comparison with LMB2 model, detachment was severer at all range of the depth of the glomeruli in LMB2+UUO contralateral kidney and LMB2+UNx model.
Conclusion
Extent of glomerular filtrate may regulate the length and the localization of detachment of injured podocyte. Up to some threshold, increase in glomerular filtrate may enhance the tendency of the lesion as a local event. Excessive glomerular filtrate beyond the autoregulation by glomerulus, as presumed in LMB2+UNx model in the study, may change the pattern of podocyte detachment that accelerates FSGS.