Journal Article

Individual differences in renal ACE activity in healthy rats predict susceptibility to adriamycin-induced renal damage

Mieneke Rook, A. Titia Lely, Andrea B. Kramer, Harry van Goor and Gerjan Navis

in Nephrology Dialysis Transplantation

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

Volume 20, issue 1, pages 59-64
Published in print January 2005 | ISSN: 0931-0509
Published online November 2004 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfh579
Individual differences in renal ACE activity in healthy rats predict susceptibility to adriamycin-induced renal damage

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Background. In man, differences in angiotensin-converting enzyme (ACE) levels, related to ACE (I/D) genotype, are associated with renal prognosis. This raises the hypothesis that individual differences in renal ACE activity are involved in renal susceptibility to inflicted damage. Therefore, we studied the predictive effect of renal ACE activity for the severity of renal damage induced by a single injection of adriamycin in rats.

Methods. Renal ACE activity (Hip-His-Leu cleavage by cortical homogenates) was determined by renal biopsy in 27 adult male Wistar rats. After 1 week of recovery, proteinuria was induced by adriamycin [1.5 mg/kg intravenously (i.v.) n = 18; controls, saline i.v. n = 9]. Proteinuria was measured every 2 weeks. After 12 weeks, rats were sacrificed and their kidneys harvested.

Results. As anticipated, adriamycin elicited nephrotic range proteinuria, renal interstitial damage and mild focal glomerulosclerosis. Baseline renal ACE positively correlated with the relative rise in proteinuria after adriamycin (r = 0.62, P<0.01), renal interstitial α-smooth muscle actin (r = 0.49, P<0.05), interstitial macrophage influx (r = 0.56, P<0.05), interstitial collagen III (r = 0.53, P<0.05), glomerular α-smooth muscle actin (r = 0.74, P<0.01) and glomerular desmin (r = 0.48, P<0.05). Baseline renal ACE did not correlate with focal glomerulosclerosis (r = 0.22, NS). In controls, no predictive values for renal parameters were observed.

Conclusion. Individual differences in renal ACE activity predict the severity of adriamycin-induced renal damage in this outbred rat strain. This supports the assumption that differences in renal ACE activity predispose to a less favourable course of renal damage.

Keywords: ACE; adriamycin nephrosis; proteinuria; renal ACE activity; renal damage; Wistar rats

Journal Article.  3886 words.  Illustrated.

Subjects: Nephrology

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