The use of electron microscopy in the diagnosis of focal segmental glomerulosclerosis: are current pathological techniques missing important abnormalities in the glomerular basement membrane?

Abstract

Background: There is an increasing appreciation that variants of the COL4A genes may be associated with the development of focal segmental glomerulosclerosis (FSGS). On electron microscopy, such variants may produce characteristic changes within the glomerular basement membrane (GBM). These changes may be missed if glomerular lesions histologically diagnosed as FSGS on light microscopy are not subjected to electron microscopy. Methods: We conducted a retrospective cohort analysis of all patients presenting to two hospitals who received a primary histological diagnosis of FSGS to see if these samples underwent subsequent electron microscopy. Each such sample was also scrutinised for the presence of characteristic changes of an underlying type IV collagen disorder Results: A total of 43 patients were identified. Of these, only 30 underwent electron microscopy. In two samples there were histological changes detected that might have suggested the underlying presence of a type IV collagen disorder. Around one in three biopsy samples that had a histological diagnosis of FSGS were not subjected to electron microscopy. Conclusion: Renal biopsy samples that have a histological diagnosis of primary FSGS not subjected to subsequent electron microscopy may potentially miss ultrastructural changes in the GBM that could signify an underlying type IV collagen disorder as the patient’s underlying disease process. This could potentially affect both them and their families’ investigative and management decisions given potential for implications for transplant, heritability and different disease pathogenesis. This represents a gap in care which should be reflected upon and rectified via iterative standard care and unit-level quality assurance initiatives.

Management of focal segmental glomerulosclerosis in resource-limited regions

“…The management of FSGS in LLMIC may face several limitations, even exceeding those faced by Priyanka et al A recent survey revealed that, while 88% of the pediatric nephrology centers in under-resourced areas have kidney pathology services available, the analysis of the biopsy is often restricted to just LM, which significantly limits its value for excluding several primary kidney diseases [6,16].…”

Pathogenic Variants in the Genes Affected in Alport Syndrome (COL4A3–COL4A5) and Their Association With Other Kidney Conditions: A Review

“…The finding of a lamellated GBM is pathognomonic for a pathogenic COL4A5 or two COL4A3 or COL4A4 variants. However in individuals with FSGS a lamellated or thinned GBM is found less often because FSGS is often diagnosed on the basis of proteinuria without a kidney biopsy or where a kidney biopsy is performed, but the GBM was not examined, 26 .…”