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Updated: Dec 23, 2025
Glomerular Outgrowth as an Ex Vivo Assay to Analyze Pathways Involved in Parietal Epithelial Cell Activation
Published on: August 19, 2020
Morphological Features of Minimal Change Disease and Focal Segmental Glomerulosclerosis Using Repeat Biopsy and
Tomo Suzuki1,2, Kaori Kohatsu1, Wei Han1
1Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan.
Introduction:
Minimal change disease (MCD) and primary focal segmental glomerulosclerosis (FSGS) are representative podocyte diseases. The clinical cause of MCD and FSGS has not been clearly elucidated yet. However, it is important to distinguish MCD and FSGS because their prognoses and responses to treatment are quite different.
Objective:
This study aimed to examine whether parietal epithelial cell (PEC) marker and repeat biopsy are useful for diagnosing primary FSGS.
Methods:
Clinicopathological features of 17 patients with the nephrotic syndrome, who underwent kidney biopsy ≥2 times from 1975 to 2017, and had MCD or FSGS were analyzed using PAX8. We defined patients with PAX8+ cells as PAX8+ and the remainder as PAX8- patients. Three cases of sample insufficiency and 1 non-steroid-resistant or frequently relapsing case indicated for repeat biopsy were excluded.
Results:
Among the 13 patients studied, 4 were PAX8+ and 9 were PAX8- (median age: 41 and 46 years, -respectively, at first biopsy). PAX8+ and PAX8- patients showed no significant differences in clinical data and histological diagnosis except for a significant difference in histological diagnosis at the second biopsy. The number of PAX8+ patients increased to 6. Unlike the first biopsy results, FSGS was present in 5 of 6 (83.3%) PAX8+ patients; MCD occurred in all 7 (100%) PAX8- patients. Three of 6 (50.0%) PAX8+ patients undergoing repeat biopsy were steroid resistant; no (0%) PAX8- patient was steroid resistant. All cases of final FSGS diagnosis were PAX8+ at the first or second biopsy. Only 1 PAX8+ MCD patient was steroid resistant. All PAX8- MCD patients were frequently relapsing.
Conclusions:
More PAX8+ patients were diagnosed with FSGS than PAX8- patients. Clinical presentation of MCD in PAX8- patients was frequently relapsing. PEC marker staining in patients with the nephrotic syndrome, e.g., MCD, may help to diagnose FSGS.
Insights
Parietal epithelial cell (PEC) marker PAX8 aids in diagnosing focal segmental glomerulosclerosis (FSGS) in nephrotic syndrome patients. PAX8-positive cases showed higher FSGS rates and steroid resistance, unlike PAX8-negative minimal change disease (MCD) cases.
Area of Science:
- Nephrology
- Pathology
- Immunohistochemistry
Background:
- Minimal change disease (MCD) and primary focal segmental glomerulosclerosis (FSGS) are distinct podocyte diseases with different prognoses.
- Distinguishing MCD from FSGS is clinically crucial due to varied treatment responses.
- The underlying causes of primary MCD and FSGS remain incompletely understood.
Purpose of the Study:
- To evaluate the diagnostic utility of parietal epithelial cell (PEC) markers in differentiating primary FSGS.
- To assess the role of repeat kidney biopsies in diagnosing FSGS.
- To investigate the correlation between PEC marker expression and clinical outcomes in nephrotic syndrome.
Main Methods:
- Analysis of clinicopathological features in 17 nephrotic syndrome patients with at least two kidney biopsies.
- Utilized PAX8 staining to identify parietal epithelial cells (PECs).
- Categorized patients into PAX8-positive (PAX8+) and PAX8-negative (PAX8-) groups for comparative analysis.
Main Results:
- FSGS was diagnosed in 83.3% of PAX8+ patients upon repeat biopsy, compared to 100% MCD in PAX8- patients.
- PAX8+ patients exhibited a higher incidence of steroid resistance (50%) than PAX8- patients (0%).
- All final FSGS diagnoses were associated with PAX8 positivity at either the first or second biopsy.
Conclusions:
- PAX8 positivity is significantly associated with FSGS diagnosis in nephrotic syndrome.
- PAX8-negative patients with MCD often present with frequently relapsing disease.
- PEC marker (PAX8) staining is a valuable tool for diagnosing FSGS in patients with nephrotic syndrome.
