Chronic kidney disease with comorbid cardiac dysfunction exacerbates cardiac and renal damage.

Abstract

To address the pathophysiological mechanisms underlying chronic kidney disease with comorbid cardiac dysfunction, we investigated renal and cardiac, functional and structural damage when myocardial infarction (MI) was applied in the setting of kidney injury (induced by 5/6 nephrectomy-STNx). STNx or Sham surgery was induced in male Sprague-Dawley rats with MI or Sham surgery performed 4 weeks later. Rats were maintained for a further 8 weeks. Rats (n = 36) were randomized into four groups: Sham+Sham, Sham+MI, STNx+Sham and STNx+MI. Increased renal tubulointerstitial fibrosis (P < 0.01) and kidney injury molecule-1 expression (P < 0.01) was observed in STNx+MI compared to STNx+Sham animals, while there were no further reductions in renal function. Heart weight was increased in STNx+MI compared to STNx+Sham or Sham+MI animals (P < 0.05), despite no difference in blood pressure. STNx+MI rats demonstrated greater cardiomyocyte cross-sectional area and increased cardiac interstitial fibrosis compared to either STNx+Sham (P < 0.01) or Sham+MI (P < 0.01) animals which was accompanied by an increase in diastolic dysfunction. These changes were associated with increases in ANP, cTGF and collagen I gene expression and phospho-p38 MAPK and phospho-p44/42 MAPK protein expression in the left ventricle. Addition of MI accelerated STNx-induced structural damage but failed to significantly exacerbate renal dysfunction. These findings highlight the bidirectional response in this model known to occur in cardiorenal syndrome (CRS) and provide a useful model for examining potential therapies for CRS.

• Authors: Shan Liu, Bing H Wang, Darren J Kelly, Henry Krum, Andrew R Kompa
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 22 Issue 1 Pg. 628-645 (01 2018) ISSN: 1582-4934 [Electronic] England
• PMID: 28994186 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Chemical References

• Biomarkers
• RNA, Messenger

Topics

• Animals
• Biomarkers (metabolism)
• Blood Pressure
• Cardiomegaly (complications, genetics, pathology, physiopathology)
• Comorbidity
• Electrocardiography
• Fibrosis
• Gene Expression Regulation
• Heart (diagnostic imaging, physiopathology)
• Heart Ventricles (pathology, physiopathology)
• Hemodynamics
• Inflammation (complications, pathology)
• Kaplan-Meier Estimate
• Kidney (pathology, physiopathology)
• Male
• Myocardial Infarction (complications, genetics, pathology, physiopathology)
• Myocardium (pathology)
• Organ Size
• RNA, Messenger (genetics, metabolism)
• Rats, Sprague-Dawley
• Renal Insufficiency, Chronic (complications, pathology, physiopathology)
• Signal Transduction