Acute kidney disease in mice is associated with early cardiovascular dysfunction
Acute kidney injury (AKI) and chronic kidney disease (CKD) are major health concerns due to their increasing incidence and high mortality. They are interconnected syndromes; AKI without recovery evolves into acute kidney disease (AKD), which can indicate an AKI-to-CKD transition. Both AKI and CKD ar...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Renal Failure |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2415510 |
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| author | Pauline Caillard Youssef Bennis Cédric Boudot Denis Chatelain Pierre Rybarczyk Agnès Boullier Sabrina Poirot Dimitri Titeca-Beauport Sandra Bodeau Gabriel Choukroun Saïd Kamel Isabelle Six Julien Maizel |
| author_facet | Pauline Caillard Youssef Bennis Cédric Boudot Denis Chatelain Pierre Rybarczyk Agnès Boullier Sabrina Poirot Dimitri Titeca-Beauport Sandra Bodeau Gabriel Choukroun Saïd Kamel Isabelle Six Julien Maizel |
| author_sort | Pauline Caillard |
| collection | DOAJ |
| description | Acute kidney injury (AKI) and chronic kidney disease (CKD) are major health concerns due to their increasing incidence and high mortality. They are interconnected syndromes; AKI without recovery evolves into acute kidney disease (AKD), which can indicate an AKI-to-CKD transition. Both AKI and CKD are associated with a risk of long-term cardiovascular complications, but whether vascular and cardiac dysfunctions can occur as early as the AKD period has not been studied extensively. In a mouse model of kidney injury (KI) with non-recovery, we performed vasoreactivity and echocardiography analyses on days 15 (D15) and 45 (D45) after KI. We determined the concentrations of two major gut-derived protein-bound uremic toxins known to induce cardiovascular toxicity—indoxyl sulfate (IS) and para-cresyl sulfate (PCS)—and the levels of inflammation and contraction markers on D7, D15, and D45. Mice with KI showed acute tubular and interstitial kidney lesions on D7 and D15 and chronic glomerulosclerosis on D45. They showed significant impairment of aorta relaxation and systolic-diastolic heart function, both on D15 and D45. Such dysfunction was associated with downregulation of the expression of two contractile proteins, αSMA and SERCA2a, with a more pronounced effect on D15 than on D45. KI was also followed by a rapid increase in IS and PCS serum concentrations and the expression induction of pro-inflammatory cytokines and endothelial adhesion molecules in serum and cardiovascular tissues. Therefore, these results highlight that AKD leads to early cardiac and vascular dysfunctions. How these dysfunctions could be managed to prevent cardiovascular events deserves further study. |
| format | Article |
| id | doaj-art-96ba26bb60574742a2ef773f4dfa8e7a |
| institution | DOAJ |
| issn | 0886-022X 1525-6049 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj-art-96ba26bb60574742a2ef773f4dfa8e7a2025-08-20T03:05:25ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492024-12-0146210.1080/0886022X.2024.2415510Acute kidney disease in mice is associated with early cardiovascular dysfunctionPauline Caillard0Youssef Bennis1Cédric Boudot2Denis Chatelain3Pierre Rybarczyk4Agnès Boullier5Sabrina Poirot6Dimitri Titeca-Beauport7Sandra Bodeau8Gabriel Choukroun9Saïd Kamel10Isabelle Six11Julien Maizel12Department of Nephrology, Dialysis and Transplantation, Amiens Medical Center, Amiens, FranceMP3CV laboratory, UR UPJV 7517, University of Picardy Jules Verne, Amiens, FranceMP3CV laboratory, UR UPJV 7517, University of Picardy Jules Verne, Amiens, FranceDepartment of Anatomopathology, Amiens Medical Center, Amiens, FranceHauts-de-France Anatomopathology Institute (i-PatH), Amiens, FranceMP3CV laboratory, UR UPJV 7517, University of Picardy Jules Verne, Amiens, FranceMP3CV laboratory, UR UPJV 7517, University of Picardy Jules Verne, Amiens, FranceDepartment of Nephrology, Dialysis and Transplantation, Amiens Medical Center, Amiens, FranceMP3CV laboratory, UR UPJV 7517, University of Picardy Jules Verne, Amiens, FranceDepartment of Nephrology, Dialysis and Transplantation, Amiens Medical Center, Amiens, FranceMP3CV laboratory, UR UPJV 7517, University of Picardy Jules Verne, Amiens, FranceMP3CV laboratory, UR UPJV 7517, University of Picardy Jules Verne, Amiens, FranceMP3CV laboratory, UR UPJV 7517, University of Picardy Jules Verne, Amiens, FranceAcute kidney injury (AKI) and chronic kidney disease (CKD) are major health concerns due to their increasing incidence and high mortality. They are interconnected syndromes; AKI without recovery evolves into acute kidney disease (AKD), which can indicate an AKI-to-CKD transition. Both AKI and CKD are associated with a risk of long-term cardiovascular complications, but whether vascular and cardiac dysfunctions can occur as early as the AKD period has not been studied extensively. In a mouse model of kidney injury (KI) with non-recovery, we performed vasoreactivity and echocardiography analyses on days 15 (D15) and 45 (D45) after KI. We determined the concentrations of two major gut-derived protein-bound uremic toxins known to induce cardiovascular toxicity—indoxyl sulfate (IS) and para-cresyl sulfate (PCS)—and the levels of inflammation and contraction markers on D7, D15, and D45. Mice with KI showed acute tubular and interstitial kidney lesions on D7 and D15 and chronic glomerulosclerosis on D45. They showed significant impairment of aorta relaxation and systolic-diastolic heart function, both on D15 and D45. Such dysfunction was associated with downregulation of the expression of two contractile proteins, αSMA and SERCA2a, with a more pronounced effect on D15 than on D45. KI was also followed by a rapid increase in IS and PCS serum concentrations and the expression induction of pro-inflammatory cytokines and endothelial adhesion molecules in serum and cardiovascular tissues. Therefore, these results highlight that AKD leads to early cardiac and vascular dysfunctions. How these dysfunctions could be managed to prevent cardiovascular events deserves further study.https://www.tandfonline.com/doi/10.1080/0886022X.2024.2415510Acute kidney injury-to-chronic kidney disease transitioncardiac dysfunctionpro-inflammatory cytokinesprotein-bound uremic toxinsvascular dysfunction |
| spellingShingle | Pauline Caillard Youssef Bennis Cédric Boudot Denis Chatelain Pierre Rybarczyk Agnès Boullier Sabrina Poirot Dimitri Titeca-Beauport Sandra Bodeau Gabriel Choukroun Saïd Kamel Isabelle Six Julien Maizel Acute kidney disease in mice is associated with early cardiovascular dysfunction Renal Failure Acute kidney injury-to-chronic kidney disease transition cardiac dysfunction pro-inflammatory cytokines protein-bound uremic toxins vascular dysfunction |
| title | Acute kidney disease in mice is associated with early cardiovascular dysfunction |
| title_full | Acute kidney disease in mice is associated with early cardiovascular dysfunction |
| title_fullStr | Acute kidney disease in mice is associated with early cardiovascular dysfunction |
| title_full_unstemmed | Acute kidney disease in mice is associated with early cardiovascular dysfunction |
| title_short | Acute kidney disease in mice is associated with early cardiovascular dysfunction |
| title_sort | acute kidney disease in mice is associated with early cardiovascular dysfunction |
| topic | Acute kidney injury-to-chronic kidney disease transition cardiac dysfunction pro-inflammatory cytokines protein-bound uremic toxins vascular dysfunction |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2415510 |
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