Abstract: FR-PO0770
Distinct Patterns of Sarcomere-Like Structures in Podocyte Foot Processes in Patients with Diverse Forms of Nephrotic Syndrome
Session Information
- Glomerular Diseases: Cell Homeostasis and Novel Injury Mechanisms
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Puapatanakul, Pongpratch, Chulalongkorn University, Bangkok, Bangkok, Thailand
- Yaseen Alsabbagh, Dema, Washington University in St Louis, St. Louis, Missouri, United States
- Genin, Guy M., Washington University in St Louis, St. Louis, Missouri, United States
- Miner, Jeffrey H., Washington University in St Louis, St. Louis, Missouri, United States
- Suleiman, Hani, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
Background
Podocytes develop synaptopodin (Synpo)/myosin IIA (MyoIIA)-positive sarcomere-like structures (SLSs) in proteinuric kidney diseases. SLSs are mechanosensitive and may prevent detachment and contribute to recovery. We have observed progressive changes in SLSs in mouse models but these are unexplored in human podocytopathies yet could have diagnostic or prognostic value.
Methods
Kidney paraffin sections from patients with nephrotic syndrome (NS) due to minimal change disease (MCD, N=4), focal segmental glomerulosclerosis (FSGS, N=5), membranous nephropathy (MN, N=5), and diabetic nephropathy (DN, N=5) were immunolabeled and imaged using high-resolution confocal microscopy to visualize podocyte foot processes (FPs) and SLSs. Nephrectomy samples (N=7) served as controls. SLSs were quantified as the area percentage of the total FP area.
Results
The SLS percentage was significantly higher in all NS entities—MCD: 71% [IQR 44–86]; FSGS: 61% [IQR 43–86]; MN: 86% [IQR 83–92]; and DN: 79% [IQR 67–80]—compared to controls (11% [IQR 9–23]) (p < 0.001). SLSs exhibited distinct patterns that mirrored the progressive changes we previously observed in mouse models (Fig. 1). The least organized Pattern 1 predominated in controls (93% [IQR 66–100]) and MCD (66% [IQR 49–92]) but was markedly reduced in FSGS (19% [IQR 16–22]), MN (7% [IQR 0–26]), and DN (22% [IQR 16–26]). Pattern 2 was more prevalent in FSGS (69% [IQR 54–79]) and MN (88% [IQR 72–95]), and to a lesser extent in DN (50% [IQR 29–56]) and MCD (30% [IQR 8–48]), while it remained low in controls (7% [IQR 0–34]). The most structurally organized Pattern 3 was observed predominantly in DN (29% [IQR 20–53]) and to a lesser degree in FSGS (12% [IQR 3–26]) but was rarely seen in MCD (1% [IQR 0–6]), MN (4% [IQR 1–6]) and was absent in controls.
Conclusion
The distinct patterns of SLSs across NS entities likely reflect differential FP adaptations to varying levels of mechanical stress. The greater podocyte loss in FSGS and DN compared to MCD and MN, along with differences in injury chronicity, may underlie these structural variations.
Funding
- NIDDK Support