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1 Nephrology and 3 Pathology Departments, Ciutat Sanitària i Universitàia de Bellvitge, and 2 Laboratory of Nephrology, Department of Medicine, University of Barcelona, 08907 L'Hospitalet, Barcelona, Spain
The present study examined the
long-term consequences of warm renal ischemia (WRI) with or without
renal ablation. Male Sprague-Dawley rats (250-300 g) were
subjected to 60 min of complete WRI by pedicle clamping and then
followed for 52 wk. Animals were organized into four groups: rats in
which both kidneys were subjected to warm ischemia (2WIK); rats with
left WRI and right nephrectomy (1WIK); uninephrectomized rats with a
left nonischemic kidney (1NK); and sham-operated rats (2NK). Additional
animals were studied at 24 h, 7 days, and 16 and 32 wk. In the
first week after WRI, rats from the 2WIK and 1WIK groups displayed a
similar degree of acute renal damage. After recovering from acute renal
failure, 1WIK rats developed progressive and severe proteinuria,
whereas it was mild in the 2WIK group, as well as in the 1NK and 2NK
groups. Only animals from the 1WIK group developed severe chronic renal failure, glomerulosclerosis, interstitial fibrosis, and upregulation of
transforming growth factor-
1 (TGF-1)
gene, which was associated with increased TGF-1 protein
expression in tubular epithelial cells, arterioles, and in areas of
mononuclear interstitial cell infiltrate. On the contrary, long-term
renal TGF-1 expression, function, and histology were
similar in 2WIK and 2NK rats. The present study shows that prolonged
bilateral WRI, when both kidneys are retained in place, induces very
mild long-term renal lesions as opposed to the severe renal scarring
observed when WRI is combined with contralateral nephrectomy.
uninephrectomy; renal fibrosis; transforming growth
factor-1; apoptosis; glomerulosclerosis
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