Document Detail


Target organ crosstalk in the Cardiorenal Syndrome: animal models.
MedLine Citation:
PMID:  22914779     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The combination of chronic kidney disease (CKD) and heart failure (HF) is associated with adverse prognosis. Although clinical studies hint at a specific bidirectional interaction between HF and CKD, insight in the pathogenesis of the cardiorenal syndrome (CRS) remains limited. We review available evidence on cardiorenal interactions from animal models of CKD and HF, and discuss several studies that employed a "double-hit" model to research organ crosstalk between heart and kidneys. Regarding cardiac changes in CKD models, parameters of cardiac remodeling are equivocal and cardiac systolic function generally remains preserved. Structural changes include hypertrophy, fibrosis and microvasculopathy. In models of heart failure, data on renal pathology are mostly limited to functional hemodynamic changes. Most "double hit" models were unable to show that combined renal and cardiac injury induces additive damage to both organs, perhaps because of short study duration or absence of organ failure. Because of this lack of 'dual failure' models, we have developed two rat models of combined CKD and HF in which renal dysfunction induced by subtotal nephrectomy preceded cardiac dysfunction. Cardiac dysfunction was induced either functionally by nitric oxide depletion, or structurally by myocardial infarction. In both models, we found that cardiac remodeling and failure was worse in CKD rats compared to controls undergoing the same cardiac insult. Variables of renal damage, like glomerulosclerosis and proteinuria were also further worsened by combined cardiorenal injury. These studies show that target organ crosstalk does occur in the CRS. These models may be useful for interventional studies in rats.
Authors:
Lennart G Bongartz; Branko Braam; Carlo A Gaillard; Maarten J Cramer; Roel Goldschmeding; Marianne C Verhaar; Pieter A Doevendans; Jaap A Joles
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-22
Journal Detail:
Title:  American journal of physiology. Renal physiology     Volume:  -     ISSN:  1522-1466     ISO Abbreviation:  Am. J. Physiol. Renal Physiol.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901990     Medline TA:  Am J Physiol Renal Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1University Medical Center Utrecht.
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