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Published on: July 19, 2018
Early peritoneal dialysis reduces lung inflammation in mice with ischemic acute kidney injury
Chris Altmann1, Nilesh Ahuja1, Carol M Kiekhaefer1
1University of Colorado Denver, Internal Medicine, Renal, Aurora, Colorado, USA.
Abstract:
Although dialysis has been used in the care of patients with acute kidney injury (AKI) for over 50 years, very little is known about the potential benefits of uremic control on systemic complications of AKI. Since the mortality of AKI requiring renal replacement therapy (RRT) is greater than half in the intensive care unit, a better understanding of the potential of RRT to improve outcomes is urgently needed. Therefore, we sought to develop a technically feasible and reproducible model of RRT in a mouse model of AKI. Models of low- and high-dose peritoneal dialysis (PD) were developed and their effect on AKI, systemic inflammation, and lung injury after ischemic AKI was examined. High-dose PD had no effect on AKI, but effectively cleared serum IL-6, and dramatically reduced lung inflammation, while low-dose PD had no effect on any of these three outcomes. Both models of RRT using PD in AKI in mice reliably lowered urea in a dose-dependent fashion. Thus, use of these models of PD in mice with AKI has great potential to unravel the mechanisms by which RRT may improve the systemic complications that have led to increased mortality in AKI. In light of recent data demonstrating reduced serum IL-6 and improved outcomes with prophylactic PD in children, we believe that our results are highly clinically relevant.
Insights
High-dose peritoneal dialysis (PD) in a mouse model of acute kidney injury (AKI) reduced lung inflammation and cleared IL-6, but did not improve kidney function. This model aids understanding of renal replacement therapy (RRT) benefits.
Area of Science:
- Nephrology
- Critical Care Medicine
- Translational Research
Background:
- Acute kidney injury (AKI) management remains challenging, with high mortality in intensive care units.
- The systemic effects of uremic toxin control via renal replacement therapy (RRT) in AKI are not well understood.
- Understanding RRT's potential to mitigate AKI complications is crucial.
Purpose of the Study:
- To develop a reproducible mouse model for studying RRT in AKI.
- To investigate the impact of peritoneal dialysis (PD) dose on AKI, systemic inflammation, and lung injury.
- To explore the mechanisms by which RRT might improve AKI outcomes.
Main Methods:
- Established low- and high-dose peritoneal dialysis (PD) models in mice with ischemic AKI.
- Assessed effects of PD on kidney injury, serum IL-6 levels, and lung inflammation.
- Measured urea clearance in a dose-dependent manner.
Main Results:
- High-dose PD did not improve AKI but significantly reduced serum IL-6 and lung inflammation.
- Low-dose PD showed no significant effects on AKI, IL-6, or lung inflammation.
- Both PD models effectively lowered urea in a dose-dependent manner.
Conclusions:
- The developed mouse models of PD in AKI are valuable for investigating RRT's systemic benefits.
- High-dose PD shows potential in reducing inflammation associated with AKI.
- Further research is warranted to elucidate RRT's role in managing AKI complications and improving patient outcomes.
