Influence of nephron mass in development of chronic renal failure after prolonged warm renal ischemia

The present study examined the long-term consequences of warm renal ischemi a (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 fol lowed for 52 wk. Animals were organized into four groups: rats in which bot h kidneys were subjected to warm ischemia (2WIK); rats with left WRI and ri ght nephrectomy (1WIK); uninephrectomized rats with a left nonischemic kidn ey (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. Afte r recovering from acute renal failure, 1WIK rats developed progressive and severe proteinuria, whereas it was mild in the 2WIK group, as well as in th e 1NK and 2NK groups. Only animals from the 1WIK group developed severe chr onic renal failure, glomerulosclerosis, interstitial fibrosis, and upregula tion of transforming growth factor-beta(1) (TGF-beta(1)) gene, which was as sociated with increased TGF-beta(1) protein expression in tubular epithelia l cells, arterioles, and in areas of mononuclear interstitial cell infiltra te. On the contrary, long-term renal TGF-beta(1) expression, function, and histology were similar in 2WIK and 2NK rats. The present study shows that p rolonged bilateral WRI, when both kidneys are retained in place, induces ve ry mild long-term renal lesions as opposed to the severe renal scarring obs erved when WRI is combined with contralateral nephrectomy.