Journal Article

IGF-I inhibitors reduce compensatory hyperfiltration in the isolated rat kidney following unilateral nephrectomy

John L. Haylor, Iain H. Mckillop, Simon D. Oldroyd and Meguid A. El Nahas

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 15, issue 1, pages 87-92
Published in print January 2000 | ISSN: 0931-0509
Published online January 2000 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/15.1.87
IGF-I inhibitors reduce compensatory hyperfiltration in the isolated rat kidney following unilateral nephrectomy

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Background. A role for insulin-like growth factor-I (IGF-I) as a mediator of renal hyperfiltration and hyperperfusion following unilateral nephrectomy (UNx) has been examined.

Methods. Adult male Wistar rats were subjected to either left UNx or sham operation. Twenty one days after surgery, the right kidney was removed under barbiturate anaesthesia, and renal function was measured ex vivo using an isolated rat kidney perfusion system. The glomerular filtration rate was assessed from the renal clearance of [14C]inulin.

Results. UNx stimulated renal growth as shown by a significantly higher (P<0.02) tissue dry weight in kidneys from UNx (0.45±0.02 g) than from sham-operated rats (0.31±0.02 g). Compensatory hyperfiltration could be detected ex vivo; kidneys obtained from UNx rats having a significantly higher (P<0.05) [14C]inulin clearance (0.75±0.08 ml/min, n=8) than kidneys obtained from sham-operated animals (0.39±0.05 ml/min, n=8). Compensatory hyperperfusion was also detected ex vivo; kidneys obtained from UNx rats having a significantly higher (P<0.05) renal perfusate flow (28.2±2.7 ml/min) than kidneys obtained from sham-operated rats (22.5±0.8 ml/min). Following perfusion with either 50 μg monoclonal IGF-I antibody (n=4) or 6.5 μM genistein (n=4), an inhibitor of tyrosine kinase, no significant difference in [14C]inulin was observed between kidneys obtained from either UNx or sham-operated rats. In contrast to hyperfiltration, renal hyperperfusion remained unaffected by the IGF-I antibody and was only reduced by 30% following genistein administration.

Conclusions. The results suggest a role for renal IGF-I as a mediator of compensatory hyperfiltration in the rat.

Keywords: IGF-I; hyperfiltration; uninephrectomy; isolated kidney; genistein; glomerular filtration rate

Journal Article.  3585 words.  Illustrated.

Subjects: Nephrology

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