Development of vascular pole-associated glomerulosclerosis in the Fawn-hooded rat.
Fawn-hooded hypertensive (FHH) rats constitute a spontaneous model of chronic renal failure with early systemic and glomerular hypertension, proteinuria, and development of focal and segmental glomerulosclerosis. The goal of the present study was to elucidate a step-by-step sequence of histopathologic events leading from an initial glomerular injury to segmental sclerosis. Segmental sclerosis in the FHH rat is consistently associated with the glomerular vascular pole. The initial injury involves the expansion of primary branches of the afferent arteriole. Apposition of those capillaries to Bowman's capsule, together with the degeneration and detachment of corresponding podocytes, allows parietal cells to attach to the naked glomerular basement membrane of this capillary, i.e., allows the formation of a tuft adhesion to Bowman's capsule. The adhesion enlarges to a broad synechia by encroaching to neighboring capillaries, apparently based on progressive podocyte degeneration at the flanks of the adhesion. Capillaries inside the adhesion--before undergoing collapse or hyalinization--appear to stay perfused for some time and to maintain some kind of filtration misdirected toward the cortical interstitium. Thereby, a prominent paraglomerular space comes into existence, enlarging in parallel with the adhesion. Toward the cortical interstitium this space is delimited by a layer of sheetlike fibroblast processes, which has obviously been assembled in response to the formation of this space. Toward the urinary space, the paraglomerular space is demarcated by the parietal epithelium and by the interface between the adhesion and the "intact" tuft remnant. Thus, the sclerotic tuft portions all become enclosed within the paraglomerular space.
Kriz
W
W
Institut für Anatomie und Zellbiologie, Universität Heidelberg, Germany.
Hosser
H
H
Hähnel
B
B
Simons
J L
JL
Provoost
A P
AP
D000818:Animals; D001160:Arterioles / Q000503:physiopathology / Q000648:ultrastructure; D005923:Glomerulosclerosis, Focal Segmental / Q000503:physiopathology*; D007668:Kidney / Q000473:pathology / Q000648:ultrastructure; D007674:Kidney Diseases / Q000473:pathology / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000503:physiopathology / Q000648:ultrastructure; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D012598:Sclerosis / Q000473:pathology / Q000503:physiopathology