CApillary DILatation Associated SegmentaL Sclerosis CADILASS a Separate Morphologic Form of Glomerular Sclerosis?
J Jackson, KA Griffin, AK Bidani, MM Picken. Loyola University Medical Center, Maywood, IL
Background: Focal and segmental glomerular sclerosis (FSGS) is the most frequent morphologic manifestation of glomerular injury seen in human biopsy material. While its etiology is diverse, the morphologic spectrum is less well defined. Nevertheless, correlation between different morphologic forms of FSGS and etiology has been attempted. Hitherto, we report a distinct form of FSGS associated with experimental nephron reduction, podocyte toxicity and hypertension and propose its recognition as a separate form of FSGS.
Design: Male rats (250g, Harlan) underwent 1/2 or 3/4 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 wks post PAN, and kidney pathology was evaluated using H&E and PAS stains.
Results: Animals developed massive proteinuria, hypertension and FSGS. While less than 10% of glomeruli showed classic FSGS, many more glomeruli (20-30%, depending on type of procedure) showed only dilatation of individual glomerular capillaries clustered within a single or adjacent glomerular segment(s). There was a spectrum of lesions ranging from a segmental capillary dilatation to a frank sclerosis. The earliest lesions showed a pure segmental glomerular capillary widening not accompanied by mesangial matrix increase or loss. Cross-sections of widened capillaries were round and appeared first in the hilar region, either centrally or laterally. In more advanced lesions there was increase in mesangial matrix and capillary and capsular adhesions. While many capillaries became obliterated, occasional distended capillaries persisted into more advance stages of sclerosis, thus supporting the notion of a transition from capillary dilatation to FSGS. Both lesions were more pronounced in 3/4 nephrectomized animals. We, therefore, propose a term capillary dilatation associated segmental sclerosis -CADILASS to refer to such lesions. This particular form of FSGS appears to be a associated with podocyte toxicity, nephron reduction and hypertension.
Conclusions: We believe that, at least in this model, CADILASS is the earliest manifestation of glomerular injury leading to sclerosis and that this morphologic variant of FSGS has hitherto not been reported. If similar changes can occur in humans, their detection can be an early, possibly treatable, marker of a progression into glomerular sclerosis in patients with nephron reduction, such as transplant recipients.
Category: Kidney (does not include tumors)
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 200, Monday Morning