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Abstract: FR-OR031

Glomerular Filtrate Promotes Cell Detachment in Podocyte Injury

Session Information

Category: Glomerular Diseases

  • 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix

Authors

  • Saga, Nobuyuki, University of Tsukuba, Tsukuba, Japan
  • Ito, Naoko, University of Tsukuba, Tsukuba, Japan
  • Sakamoto, Kazuo, University of Tsukuba, Tsukuba, Japan
  • Matsusaka, Taiji, Tokai University School of Medicine, Isehara, Kanagawa, Japan
  • Nagata, Michio, University of Tsukuba, Tsukuba, Japan
Background

Podocyte detachment is a hallmark of segmental glomerulosclerosis. Although glomerular filtrate may effectively drive cell detachment, it alone is insufficient and needs presumptive structural changes in filtration surface. We analyzed structural background that synergistically drives podocyte detachment in NEP25, a mouse model of uniform podocyte injury.

Methods

Whole glomerular profiles (73 glomeruli, n=6) in NEP25 mice with LMB2 (8-10 days) were photographed by TEM. Entire GBM in all glomeruli were classified into normal, foot process effacement (FPE) or detachment and each length per glomerulus was measured. This method enabled us to identify the localization and continuity of each change within the glomerulus. UUO was performed at day 5 in the above protocol (UUO model, n=3) to identify the effect of filtrate on detachment. Using multiphoton microscopy (MPM), decreased filtration by UUO was visualized. Glomeruli in UUO model were analyzed by TEM in the same way as above.

Results

Detachment occurred only in the glomeruli with >50% FPE lesions. The length of detachment correlated with the length of FPE. Detachment was more in deep cortex than in surface and tended to occur in limited to 1 to 2 local areas within each glomerulus. In examining 43 glomeruli with both vascular and urinary poles, detachment dominantly occurred at the side of urinary pole. Contralateral kidneys of UUO model had severe podocyte detachment, which also occurred dominantly at the urinary pole side (n=61). Filtration effectively decreased in the obstructed kidneys of UUO by MPM and these glomeruli completely lacked podocyte detachment, despite diffuse FPE by TEM (n=55). Podocyte pseudocysts were observed in the contralateral kidneys but rarely in the obstructed kidneys of UUO model.

Conclusion

1) Podocyte detachment may be caused by synergistic effects of podocyte changes, such as FPE, with hydrostatic forces by filtrate. Biological changes in podocyte that occur in “grouping” may be an additional background. 2) From the fact that the frequency and the length of detachment positively correlated with the extent of FPE and pseudocyst, the cell reaction to strengthen cell-GBM and cell-cell attachment is also a basis for podocyte detachment.