Experimental Segmental Glomerular Sclerosis with Capillary and Podocyte Cystic Dilatation – Electron Microscopic Studies
J Jackson, K Griffin, A Bidani, M Picken. Loyola Univ Med Ctr, Maywood
Background: Focal and segmental glomerular sclerosis (FSGS) is the most frequent morphologic manifestation of glomerular injury seen in human biopsy material. Its etiology is diverse and the morphologic spectrum is not well defined. Recently, attemepts have been made to dissect FSGS into specific clinico-pathologic entities based on morphology. We previously reported on a distinct form of FSGS associated with experimental nephron reduction, podocyte toxicity and hypertension. Here, we report further electron microscopic (EM) studies of this model, which shed light on the capillary wall and podocyte contributions to the development of FSGS.
Design: Male rats (∼250g, Harlan) underwent ½ and ¾ surgical nephrectomy, followed by a single dose of puromycin aminonucleoside (PAN)(75 mg/kg IP) 14 days after surgery. The animals were sacrificed at 4 weeks post PAN, and kidney pathology was evaluated using paraffin sections (H&E and PAS stains) as well as EM, using semithin and ultrathin sections.
Results: Animals developed massive proteinuria, hypertension and FSGS. While less than 10% of glomeruli showed classic FSGS, many more glomeruli (20-30% depending on the type of procedure) showed cystic changes within the tufts that were readily discernible in paraffin sections. These cystic spaces clustered within a single or adjacent glomerular segment(s). There was a spectrum of lesions ranging from segmental cystic dilatation to frank sclerosis. The earliest changes showed pure segmental cystic dilatation not associated with mesangial matrix increase or loss. Frequently, these cysts were seen first in the hilar region, either centrally or laterally. In more advanced lesions, an increase in mesangial matrix and capsular adhesions became apparent. While many cysts eventually became obliterated, some persisted into more advanced stages of sclerosis. Semithin Epon sections and further EM studies clearly demonstrated that while some of these cysts represented dilated glomerular capillaries, numerous pseudo-cysts developed within pododcytes. Their development was followed by the formation of capsular adhesions, which in turn formed a nidus for sclerosis.
Conclusions: In this model we have shown that the development of FSGS is preceeded by the development of abnormally-shaped capillary channels with capillary dilatation and characteristic cystic changes within podocytes. EM studies, in particular semithin sections, were very helpful in discerning the earliest lesions. If similar changes occur in humans, their early detection may be important for prevention.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 263, Monday Morning