Alport's syndrome. Emphasizing electron microscopic studies of the glomerulus

Area of Science:

• Nephrology
• Pathology
• Genetics

Background:

• The exact cause and early kidney pathology in Alport's syndrome are not well understood.
• Histologic findings in later stages are debated, and the initial site of damage is obscure.

Purpose of the Study:

• To investigate the early ultrastructural changes in the kidney in patients with Alport's syndrome.
• To elucidate the site of initial pathologic alterations in the renal glomeruli.

Main Methods:

• Ultrastructural examination of renal biopsy tissue from 8 patients diagnosed with Alport's syndrome.
• Light microscopy and electron microscopy were utilized to assess glomerular morphology.

Main Results:

• Striking glomerular lesions were observed, including basement membrane thickening and lamina densa splitting/splintering, even in biopsies with minimal light microscopy abnormalities.
• Flocculent basement membrane precipitate and extreme thinning of the lamina densa were noted; dense deposits were absent.
• Focal-local sclerosis was a frequent finding on both light and electron microscopy.

Conclusions:

• The glomerular basement membrane appears to be a primary site of early pathologic change in Alport's syndrome.
• The absence of dense deposits supports previous findings of absent immunoglobulins in affected glomeruli.
• The precise cause of these observed glomerular lesions remains unknown.