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Immune Cells Are Differentially Modulated in the Heart and the Kidney during the Development of Cardiorenal Syndrome
Imara Caridad Stable Vernier1, Raquel Silva Neres-Santos1, Vinicius Andrade-Oliveira2
1Laboratory of Cardiovascular Immunology, Center of Natural and Human Sciences (CCNH), Federal University of ABC, São Paulo 09210-580, Brazil.
Insights
Acute kidney injury (AKI) triggers immune cell changes in the heart and kidneys, contributing to cardiorenal syndrome type 3 (CRS 3). This study reveals immune system activation linking kidney and cardiac injury.
Area of Science:
- Immunology
- Nephrology
- Cardiology
Background:
- Cardiorenal syndrome type 3 (CRS 3) involves acute kidney injury (AKI) leading to acute cardiac injury.
- The immune system's role in CRS 3 pathogenesis is not fully understood.
- Immune cell dynamics in kidney and heart tissues during AKI-induced CRS 3 require characterization.
Purpose of the Study:
- To investigate macrophage, T lymphocyte, and B lymphocyte populations in renal and cardiac tissues following AKI induced by renal ischemia-reperfusion (I/R).
- To elucidate the immune response and inflammatory mediators involved in the development of CRS 3.
Main Methods:
- Utilized a unilateral renal I/R model in C57BL/6 mice, with reperfusion periods of 3, 8, and 15 days.
- Employed flow cytometry to identify and quantify immune cell populations.
- Applied RT-qPCR to assess gene expression profiles of inflammatory mediators.
Main Results:
- AKI induced by renal I/R significantly increased TCD4+, TCD8+ lymphocytes, and M1 macrophages in renal tissue.
- A decrease in B cells was observed in cardiac tissue.
- Renal tissue exhibited a repair response with Foxp3 activation, while cardiac tissue showed an inflammatory profile driven by IL-17RA and IL-1β.
Conclusions:
- AKI activates and recruits immune cells, including lymphocytes and macrophages, to both renal and cardiac tissues.
- Pro-inflammatory mediators like IL-17RA and IL-1β contribute to cardiac inflammation in the context of AKI.
- The immune system acts as a critical link between renal and cardiac dysfunction in CRS 3.
Abstract:
Cardiorenal syndrome type 3 (CRS 3) occurs when there is an acute kidney injury (AKI) leading to the development of an acute cardiac injury. The immune system is involved in modulating the severity of kidney injury, and the role of immune system cells in the development of CRS 3 is not well established. The present work aims to characterize the macrophage and T and B lymphocyte populations in kidney and heart tissue after AKI induced by renal I/R. Thus, C57BL/6 mice were subjected to a renal I/R protocol by occlusion of the left renal pedicle (unilateral) for 60 min, followed by reperfusion for 3, 8 and 15 days. The immune cell populations of interest were identified using flow cytometry, and RT-qPCR was used to evaluate gene expression. As a result, a significant increase in TCD4+, TCD8+ lymphocytes and M1 macrophages to the renal tissue was observed, while B cells in the heart decreased. A renal tissue repair response characterized by Foxp3 activation predominated. However, a more inflammatory profile was shown in the heart tissue influenced by IL-17RA and IL-1β. In conclusion, the AKI generated by renal I/R was able to activate and recruit T and B lymphocytes and macrophages, as well as pro-inflammatory mediators to renal and cardiac tissue, showing the role of the immune system as a bridge between both organs in the context of CRS 3.
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