Abstract
IntroductionFocal segmental glomerular sclerosis (FSGS) is caused by podocyte injury. It is characterized by obliteration of glomerular capillary tufts with increased extracellular matrix (ECM). Altered communication between podocytes and glomerular endothelial cells (ECs) contributes to sclerosis progression. We focused on EC injury in the FSGS.MethodsA total of 29 FSGS and 18 control biopsy specimens were assessed for clinicopathologic characteristics. CD34 (a marker for EC)-positive capillaries and ECM accumulation were evaluated quantitatively for each variant using computer-assisted image analysis.ResultsThe estimated glomerular filtration rate (eGFR) in the FSGS group was significantly lower than that in the control group. The frequency of FSGS variants was 51.7% for cellular; 13.8% for perihilar (PH), tip, and not otherwise specified (NOS); and 6.9% for collapsing. Regarding sclerotic lesions in all FSGS, narrowing or loss of CD34-positive capillaries was observed. Electron microscopy results showed loss of fenestrae, subendothelial space enlargement, and cytoplasmic swelling, indicating EC injury. Computer-assisted image analysis revealed significantly smaller areas of glomerular capillaries in FSGS with or without sclerotic lesions, with increased ECM. Moreover, in comparison with each variant, narrowed capillaries and ECM accumulation were most prominent in the collapsing variant, whereas the tip variant had the least change.ConclusionEC injury was observed in all FSGS cases, not only in sclerotic lesions but also in nonsclerotic lesions. Severity of EC injury may vary in each variant due to diverse alterations of glomerular capillary networks.
Highlights
Focal segmental glomerular sclerosis (FSGS) is caused by podocyte injury
endothelial cells (ECs) injury was observed in all FSGS cases, in sclerotic lesions and in nonsclerotic lesions
We reported that EC injury was observed in all cases of membranous nephropathy, and EC injury was more severe in cases with segmental sclerosis than in cases without segmental sclerosis.[21]
Summary
A total of 29 FSGS and 18 control biopsy specimens were assessed for clinicopathologic characteristics. Ethics This study was performed in accordance with the Declaration of Helsinki and was approved by the Ethics Review Committee of Nippon Medical School (approval number: B-2020-167). M Morita et al.: Glomerular Endothelial Cell Injury in FSGS from all patients or from their parents or legal guardians if patients were under 18 years of age. Case Selection A total of 29 cases diagnosed with having primary FSGS were retrospectively identified from a series of renal biopsies performed at the Nippon Medical School between 1997 and 2013. 18 patients diagnosed with having minor glomerular abnormalities (10 with NS and 8 with persistent proteinuria) were included in the control group for computer-assisted morphometric analysis, with no significant difference in age.
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