Involvement of renal ACE activity in proteinuria-associated renal damage in untreated and treated adriamycin nephrotic rats

H Bos, GD Laverman, RH Henning, AT Tiebosch, PE de Jong, D de Zeeuw, G Navis*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

15 Citations (Scopus)

Abstract

Proteinuria is assumed to play a pathogenetic role in progressive renal damage. Angiotensin-converting enzyme (ACE) inhibition reduces proteinuria and provides renoprotection. This suggests that ACE activity might play a pathogenetic role in the development of proteinuria-induced renal structural damage. We investigated this hypothesis in untreated and treated established adriamycin nephrosis, a model of proteinuria-induced renal damage.

In a time-course experiment, the development of renal structural damage in untreated adriamycin nephrotic rats was paralleled by a significant rise in renal ACE activity. Moreover, on cross-sectional analysis, a consistent positive correlation between renal, but not plasma, ACE activity and proteinuria, focal glomerulosclerosis and interstitial injury was present. Notably, these associations were present, not only in the untreated condition, but also during intervention with either ACE inhibition or AT(1)-receptor antagonism. Interestingly, we found that higher renal ACE activity is associated with more severe renal damage for a given amount of proteinuria, suggesting that renal ACE activity may be either a permissive or a promoting factor in the processes by which proteinuria eventually leads to renal structural damage. This relationship was abolished by renin-angiotensin system (RAS)-blockade, suggesting that RAS-mediated effects are involved in the relationship between renal ACE activity and proteinuria-induced renal damage.

In conclusion, in untreated as well as treated adriamycin nephrotic rats, renal ACE activity is closely associated with renal outcome. This association appears to be independent of the specific mode of blockade of the RAS. Renal ACE activity is a consistent marker of individual differences in proteinuria-associated renal damage: further studies are needed to investigate a possible pathogenetic role in renal damage.

Original languageEnglish
Pages (from-to)106-112
Number of pages7
JournalJournal of the Renin-Angiotensin-Aldosterone System
Volume4
Issue number2
Publication statusPublished - Jun-2003

Keywords

  • renal ACE
  • proteinuria
  • treatment
  • ACE inhibition
  • ANGIOTENSIN-CONVERTING ENZYME
  • TERM ANTIPROTEINURIC RESPONSE
  • INDUCED GLOMERULOSCLEROSIS
  • GFR DECLINE
  • INHIBITION
  • DISEASE
  • INJURY
  • KIDNEY

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