title: Morphologic changes suggesting abnormal renal differentiation in congenital nephrotic syndrome.
abstract: Retrograde differentiation (or dedifferentiation) has recently been proposed as a pathogenetic mechanism involved also in various renal diseases. Here we studied whether evidence of these mechanisms can be found in the kidneys of patients with congenital nephrotic syndrome of the Finnish type (CNF). These patients show isolated massive proteinuria but no primary symptoms from any other organ systems. For the analysis we used antibody markers of early (fibronectin, stem cell factor, Wilms' tumor gene product, cytokeratin) and later (laminin, midgestation and kidney, heparin binding growth-associated molecule) stages of nephron differentiation as well as for apoptosis (acridine orange staining), rescue from apoptosis (anti-Bcl-2 antibodies) and cell proliferation (antibodies to proliferating cell nuclear antigen). In the peritubular spaces atypically organized areas were found which appeared positive with markers of low stages of differentiation, but neither abnormal cell proliferation nor activation of the apoptotic pathway could be detected. As morphologic signs of abnormal tissue organization, we found clusters of tightly compacted and large glomeruli corresponding to the size of two to three normal glomeruli. However, all individual glomerular cell compartments (mesangial, endothelial, visceral epithelial cells) appeared balanced in relative cell numbers. Together these results may indicate abnormal early mesenchymoepithelial tissue interaction leading to excessive and poorly organized formation of glomeruli. This could be causally related also to the serious functional immaturity of CNF kidneys presented as isolated proteinuria.
authors.affiliation: Haartman Institute, Department of Bacteriology and Immunology, University of Helsinki, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Haltia
authors.forename: M L
authors.initials: ML
authors.lastname: Solin
authors.forename: C
authors.initials: C
authors.lastname: Holmberg
authors.forename: J
authors.initials: J
authors.lastname: Reivinen
authors.forename: A
authors.initials: A
authors.lastname: Miettinen
authors.forename: H
authors.initials: H
authors.lastname: Holthöfer
mesh_terms: D000328:Adult; D015415:Biomarkers; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007668:Kidney / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology*; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology; D009399:Nephrons / Q000002:abnormalities / Q000378:metabolism / Q000473:pathology; D009404:Nephrotic Syndrome / Q000151:congenital* / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000378:metabolism; D025721:WT1 Proteins
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D025721:WT1 Proteins