Document Detail

Effect of proteinuria reduction on prevention of focal glomerulosclerosis by angiotensin-converting enzyme inhibition is modifiable.
MedLine Citation:
PMID:  10412735     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Proteinuria is associated with a progressive loss of renal function; we recently found that both intrarenal effects of proteinuria and the state of systemic nephrosis play an independent role in proteinuria-induced renal damage. Reduction of proteinuria is an important mechanism underlying the renoprotective effect of angiotensin-converting enzyme inhibition (ACEi). Both the reduction of proteinuria and the attenuation of the systemic state of nephrosis may be involved in the renoprotection by ACEi. METHODS: This article entails a post hoc analysis of a previous study on the renoprotective effect of ACEi lisinopril in adriamycin nephrosis. It was attempted to modify therapeutic efficacy of ACEi by increasing lisinopril dose and by dietary sodium restriction, respectively. In this analysis, we aimed to delineate the contribution of proteinuria reduction and the reduction of other intermediate parameters such as hyperlipidemia and blood pressure on the protection against focal glomerulosclerosis (FGS). RESULTS: We found that in adriamycin nephrosis, ACEi significantly reduced proteinuria, lipids, and blood pressure and provided protection against FGS. Treatment modification by increasing the lisinopril dose resulted in a further reduction of FGS without significant effects on intermediate parameters (proteinuria, hyperlipidemia, and blood pressure), whereas surprisingly, treatment modification by sodium restriction resulted in a further attenuation of intermediate parameters, without additional protection against FGS. CONCLUSIONS: The renoprotective benefit of an obtained attenuation of intermediate parameters is modified by other factors. Further optimization of renoprotective therapy requires identification of such factors and explicit consideration of therapeutic efficacy on intermediate parameters as well as hard end points.
E de Boer; G Navis; F H Wapstra; P E de Jong; D de Zeeuw
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Kidney international. Supplement     Volume:  71     ISSN:  0098-6577     ISO Abbreviation:  Kidney Int. Suppl.     Publication Date:  1999 Jul 
Date Detail:
Created Date:  1999-09-15     Completed Date:  1999-09-15     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7508622     Medline TA:  Kidney Int Suppl     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  S42-6     Citation Subset:  IM    
Groningen Institute for Drug Studies, State University Hospital, The Netherlands.
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MeSH Terms
Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
Blood Pressure / drug effects
Cholesterol / blood
Dose-Response Relationship, Drug
Doxorubicin / adverse effects
Glomerulosclerosis, Focal Segmental / mortality,  prevention & control*
Lisinopril / therapeutic use
Peptidyl-Dipeptidase A / drug effects
Proteinuria / chemically induced,  drug therapy*,  urine
Rats, Wistar
Sodium, Dietary / pharmacology
Survival Analysis
Triglycerides / blood
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Sodium, Dietary; 0/Triglycerides; 23214-92-8/Doxorubicin; 57-88-5/Cholesterol; 83915-83-7/Lisinopril; EC A

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