Glomerular TRPC5 and Palladin immunohistochemical profiling in focal segmental glomerulosclerosis: tissue heterogeneity and exploratory clinical associations (PRIME-PATH I)
- 1Department of Nephrology, Gazi University Faculty of Medicine, Ankara, Türkiye
- 2Department of Pathology, Gazi University Faculty of Medicine, Ankara, Türkiye
Abstract
Introduction: Focal segmental glomerulosclerosis (FSGS) is a shared histopathologic pattern arising from biologically diverse podocyte injuries. Transient receptor potential canonical 5 (TRPC5) has been implicated in calcium–cytoskeletal signaling and entered clinical evaluation, whereas Palladin is an actin-associated scaffold involved in cytoskeletal organization. Their glomerular immunohistochemical patterns in human FSGS remain poorly characterized.
Methods: In this single-center retrospective biopsy cohort, 182 adults with biopsy-diagnosed FSGS between 2010 and 2020 were screened; 103 with adequate archived tissue, at least two evaluable glomeruli, and at least 24 months of follow-up comprised the analytic cohort. TRPC5 was scored as 0 (nuclear-only/no reproducible capillary-granular staining), 1 (discontinuous capillary-granular staining), or 2 (continuous/diffuse capillary-granular staining); scores 1–2 were grouped as TRPC5-positive. Palladin showed capillary-granular immunoreactivity in all evaluable biopsies and was classified as discontinuous or diffuse. Twenty-four-month treatment response was based on 24-hour urinary protein excretion. Poor response was the primary clinical outcome; kidney failure (maintenance dialysis or kidney transplantation) was evaluated during follow-up.
Results: TRPC5 immunoreactivity was present in 70/103 biopsies (68.0%) and absent in 33/103 (32.0%); Palladin staining was diffuse in 75/103 (72.8%) and discontinuous in 28/103 (27.2%). Poor response occurred in 54/103 (52.4%) and kidney failure in 33/103 (32.0%). TRPC5-positive patients more often had poor response (64.3% vs. 27.3%; P < 0.001) and kidney failure (42.9% vs. 9.1%; P < 0.001). In the primary adjusted model, TRPC5 positivity was associated with poor response (OR, 3.28; 95% CI, 1.13–9.52; P = 0.029) and kidney failure (OR, 5.51; 95% CI, 1.25–24.23; P = 0.024). Estimates were similar after adjustment for global glomerulosclerosis but attenuated and imprecise after IFTA adjustment (n = 70). Palladin distribution was not independently associated with either outcome and did not improve model fit.
Conclusion: PRIME-PATH I identifies heterogeneous glomerular TRPC5 immunoreactivity as a tissue-level phenotype within morphologically defined FSGS, with Palladin providing complementary cytoskeletal staining-distribution information. These associations are hypothesis-generating, and independent prognostic value remains uncertain after accounting for chronic structural injury. The findings do not establish functional TRPC5 activation or treatment predictiveness but support prospective studies integrating etiologic classification, cell-specific localization, pathway activity, and therapeutic response.
Related
- VEGF-A Immunohistochemical Expression Across Appendiceal Epithelial Lesions: A Retrospective Exploratory Study
- Set binding factor 1 (SBF1/MTMR5) as a potential novel target in colorectal cancer: an exploratory immunohistochemical and bioinformatics study.
- Comparative histopathological and immunohistochemical features of central nervous system and pulmonary tuberculosis: an exploratory retrospective study.
- Immunohistochemical Expression of Proliferating Cell Nuclear Antigen in Invasive Breast Carcinoma: Associations With Histological Grade and Ki-67 Expression.
- Associations Between Upright Cardiovascular-Autonomic Characteristics, Temporal Gait Measures, and Mediolateral Plantar Center-of-Force Measures in Adults with Developmental Disabilities: An Exploratory Cross-Sectional Study
BibTeX
@article{ural2026glomerular,
title = {{Glomerular TRPC5 and Palladin immunohistochemical profiling in focal segmental glomerulosclerosis: tissue heterogeneity and exploratory clinical associations (PRIME-PATH I)}},
author = {Zeynep Ural and Betül Ogüt and Ipek Isık Gönül and Galip Güz},
journal = {Frontiers in Medicine},
year = {2026},
month = oct,
doi = {10.3389/fmed.2026.1924319},
url = {https://doi.org/10.3389/fmed.2026.1924319},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Glomerular TRPC5 and Palladin immunohistochemical profiling in focal segmental glomerulosclerosis: tissue heterogeneity and exploratory clinical associations (PRIME-PATH I)
AU - Zeynep Ural
AU - Betül Ogüt
AU - Ipek Isık Gönül
AU - Galip Güz
PY - 2026
DA - 2026/10/22
JO - Frontiers in Medicine
DO - 10.3389/fmed.2026.1924319
UR - https://doi.org/10.3389/fmed.2026.1924319
AB - Introduction: Focal segmental glomerulosclerosis (FSGS) is a shared histopathologic pattern arising from biologically diverse podocyte injuries. Transient receptor potential canonical 5 (TRPC5) has been implicated in calcium–cytoskeletal signaling and entered clinical evaluation, whereas Palladin is an actin-associated scaffold involved in cytoskeletal organization. Their glomerular immunohistochemical patterns in human FSGS remain poorly characterized. Methods: In this single-center retrospective biopsy cohort, 182 adults with biopsy-diagnosed FSGS between 2010 and 2020 were screened; 103 with adequate archived tissue, at least two evaluable glomeruli, and at least 24 months of follow-up comprised the analytic cohort. TRPC5 was scored as 0 (nuclear-only/no reproducible capillary-granular staining), 1 (discontinuous capillary-granular staining), or 2 (continuous/diffuse capillary-granular staining); scores 1–2 were grouped as TRPC5-positive. Palladin showed capillary-granular immunoreactivity in all evaluable biopsies and was classified as discontinuous or diffuse. Twenty-four-month treatment response was based on 24-hour urinary protein excretion. Poor response was the primary clinical outcome; kidney failure (maintenance dialysis or kidney transplantation) was evaluated during follow-up. Results: TRPC5 immunoreactivity was present in 70/103 biopsies (68.0%) and absent in 33/103 (32.0%); Palladin staining was diffuse in 75/103 (72.8%) and discontinuous in 28/103 (27.2%). Poor response occurred in 54/103 (52.4%) and kidney failure in 33/103 (32.0%). TRPC5-positive patients more often had poor response (64.3% vs. 27.3%; P < 0.001) and kidney failure (42.9% vs. 9.1%; P < 0.001). In the primary adjusted model, TRPC5 positivity was associated with poor response (OR, 3.28; 95% CI, 1.13–9.52; P = 0.029) and kidney failure (OR, 5.51; 95% CI, 1.25–24.23; P = 0.024). Estimates were similar after adjustment for global glomerulosclerosis but attenuated and imprecise after IFTA adjustment (n = 70). Palladin distribution was not independently associated with either outcome and did not improve model fit. Conclusion: PRIME-PATH I identifies heterogeneous glomerular TRPC5 immunoreactivity as a tissue-level phenotype within morphologically defined FSGS, with Palladin providing complementary cytoskeletal staining-distribution information. These associations are hypothesis-generating, and independent prognostic value remains uncertain after accounting for chronic structural injury. The findings do not establish functional TRPC5 activation or treatment predictiveness but support prospective studies integrating etiologic classification, cell-specific localization, pathway activity, and therapeutic response.
SN - 2296-858X
ER -