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[An electron microscopic study of circumferential mesangial interposition in various renal diseases]
1Department of Medicine (II), Niigata University School of Medicine, Japan.
Abstract:
It has been reported that circumferential mesangial interposition (CMI) is an important morphological feature suggesting the progression of glomerulosclerosis in glomerular disease. The relation between CMI and its associated lesions was investigated in various renal diseases by electron microscopy. In 276 patients, of whom the glomeruli were observed by electron microscopy, CMI was observed non-specifically in 48 patients with various glomerular diseases (IgA nephropathy, 11; non-IgA glomerulonephritis, 1; membranoproliferative glomerulonephritis, 8; membranous nephropathy, 5; lupus glomerulonephritis, 12; toxemia of pregnancy, 2; diabetic nephropathy, 7; mitomycin nephropathy, 1; and Seckel's dwarfism patients, 1). The glomeruli with CMI showed a marked increase in mesangial matrix, as well as various grades of mesangial cell proliferation. Mesangiolysis associated with subendothelial widening was observed in a lesion of CMI in most cases. This phenomenon appears to be an initial alteration that conducts proliferated cells to the peripheral portion of a capillary loop. Localized severe thinning of the glomerular basement membrane was frequently combined with CMI, particularly in IgA nephropathy patients. Endothelial cells were occasionally interposed into the widened subendothelial space. Subendothelial deposits were noticed in the CMI lesion, particularly in MPGN patients. In conclusion, in the process of glomerulosclerosis progression in various glomerular diseases, lytic and edematous changes initially occur in the mesangio-subendothelial system (mesangiolysis and subendothelial widening), then proliferating mesangial cells extend into the widened space (between GBM and endothelial cells), and reach the peripheral portion of a capillary loop.
Insights
Circumferential mesangial interposition (CMI) is a key feature in glomerulosclerosis progression. This electron microscopy study reveals CMI involves mesangiolysis and cell proliferation, indicating early changes in glomerular disease.
Area of Science:
- Nephrology
- Pathology
- Electron Microscopy
Context:
- Glomerulosclerosis is a common pathway in chronic kidney disease.
- Circumferential mesangial interposition (CMI) is recognized as a significant morphological marker.
- Understanding CMI's role is crucial for diagnosing and managing glomerular diseases.
Purpose:
- To investigate the relationship between CMI and associated glomerular lesions using electron microscopy.
- To elucidate the pathogenetic sequence of CMI in various glomerular diseases.
- To identify early ultrastructural changes indicative of glomerulosclerosis progression.
Summary:
- Electron microscopy analysis of 276 patients revealed CMI in 48 cases across diverse glomerular diseases.
- CMI is characterized by increased mesangial matrix, mesangial cell proliferation, and mesangiolysis with subendothelial widening.
- Associated findings include glomerular basement membrane thinning, endothelial cell interposition, and subendothelial deposits, particularly in IgA nephropathy and MPGN.
Impact:
- This study clarifies the initial ultrastructural events in glomerulosclerosis, involving mesangiolysis and subendothelial widening.
- CMI represents a dynamic process where mesangial cells migrate to the capillary loop periphery.
- Findings enhance understanding of glomerular disease pathogenesis and progression, potentially guiding future therapeutic strategies.