Browsing by Author "Fox, Benjamin M."

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Early peritoneal dialysis reduces lung inflammation in mice with ischemic acute kidney injury
    (Elsevier, 2017-08) Altmann, Chris; Ahuja, Nilesh; Kiekhaefer, Carol M.; Andres Hernando, Ana; Okamura, Kayo; Bhargava, Rhea; Duplantis, Jane; Kirkbride-Romero, Lara A.; Huckles, Jill; Fox, Benjamin M.; Kahn, Kashfi; Soranno, Danielle E.; Gil, Hyo-wook; Teitelbaum, Isaac; Faubel, Sarah; Pediatrics, School of Medicine
    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.
  • Thumbnail Image
    Item
    Metabolomics assessment reveals oxidative stress and altered energy production in the heart after ischemic acute kidney injury in mice
    (Elsevier, 2019-03) Fox, Benjamin M.; Gil, Hyo-Wook; Kirkbride-Romeo, Lara; Bagchi, Rushita A.; Wennersten, Sara A.; Haefner, Korey R.; Skrypnyk, Nataliya I.; Brown, Carolyn N.; Soranno, Danielle E.; Gist, Katja M.; Griffin, Benjamin R.; Jovanovich, Anna; Reisz, Julie A.; Wither, Matthew J.; D'Alessandro, Angelo; Edelstein, Charles L.; Clendenen, Nathan; McKinsey, Timothy A.; Altmann, Christopher; Pediatrics, School of Medicine
    Acute kidney injury (AKI) is a systemic disease associated with widespread effects on distant organs, including the heart. Normal cardiac function is dependent on constant ATP generation, and the preferred method of energy production is via oxidative phosphorylation. Following direct ischemic cardiac injury, the cardiac metabolome is characterized by inadequate oxidative phosphorylation, increased oxidative stress, and increased alternate energy utilization. We assessed the impact of ischemic AKI on the metabolomics profile in the heart. Ischemic AKI was induced by 22 minutes of renal pedicle clamping, and 124 metabolites were measured in the heart at 4 hours, 24 hours, and 7 days post-procedure. 41% of measured metabolites were affected, with the most prominent changes observed 24 hours post-AKI. The post-AKI cardiac metabolome was characterized by amino acid depletion, increased oxidative stress, and evidence of alternative energy production, including a shift to anaerobic forms of energy production. These metabolomic effects were associated with significant cardiac ATP depletion and with echocardiographic evidence of diastolic dysfunction. In the kidney, metabolomics analysis revealed shifts suggestive of energy depletion and oxidative stress, which were reflected systemically in the plasma. This is the first study to examine the cardiac metabolome after AKI, and demonstrates that effects of ischemic AKI on the heart are akin to the effects of direct ischemic cardiac injury.