Ultrastructural Changes in 5/6 Nephrectomy Rats Correlate with the Progression of Ablative Nephropathy
Ayhan Ozcan, Kyle Ware, Qamri Zahida, Edward P Calomeni, Tibor Nadasdy, Anjali A Satoskar, Gyongyi Nadasdy, Brad Rovin, Lee A Hebert, Sergey V Brodsky,. Gulhane Military Medical Academy, School of Medicine, Ankara, Turkey; Ohio State University, Columbus, OH
Background: Chronic kidney disease (CKD) is a worldwide health problem with a rising incidence and poor outcomes. 5/6 nephrectomy (Nx) is an established model of ablative nephropathy with progressive focal segmental glomerular sclerosis (FSGS). Despite well-documented light microscopy changes, no detailed information about ultrastructural changes in progressive FSGS is available. The aim of the current study was to characterize electron microscopy findings in 5/6 Nx rats at different stages of FSGS.
Design: Sprague Dawley rats underwent 5/6 Nx and were monitored until week 23 after the ablative surgery. Serum (SC) and urine creatinine, hematuria and proteinuria were measured weekly. Kidney morphology (including electron microscopy) was evaluated at 3, 8 and 23 weeks after the ablative surgery.
Results: 5/6 Nx rats had progressive proteinuria, hematuria, SC increase and FSGS. Ultrastructurally, the glomerular basement membrane (GBM) thickness was increased at late, but not early stages of FSGS (153±10 nm, 158±9 nm, 151±6 nm and 190±16 nm in control, 3, 8 and 23 weeks after the ablative surgery, respectively). No evident changes in the GBM texture were seen. Cytoplasmic swelling of the glomerular capillary loop endothelial cells was noted. Segmentally, glomerular capillary loop endothelial cell fenestration was decreased. Podocyte foot processes did not show relevant effacement even at late FSGS stages. The GBM thickness significantly correlated with SC (R2=0.721, p<0.0001), hematuria (R2=0.627, p<0.0004) and to a lesser degree with urinary protein/creatinine ratio (R2=0.312, p<0.024).
Conclusions: 1) The GBM thickness increases with the progression of FSGS in 5/6 Nx rats. 2) Progressive swelling and loss of fenestration in the glomerular capillary loop endothelial cells indicates cellular damage, probably secondary to increased glomerular hyperfiltration/hyperperfusion injury. 3) Our findings may be useful for understanding the pathogenesis of ablative nephropathy and FSGS in humans.
Category: Kidney (does not include tumors)
Monday, March 4, 2013 1:00 PM
Poster Session II # 247, Monday Afternoon