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Kidney Week

Abstract: SA-PO615

The Pathophysiology of Augmented Renal Clearance Similarly Affects Hepatic Clearance in Critically Ill Trauma Patients

Session Information

  • Pharmacology
    October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

  • 1700 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

  • Coritsidis, George N., Elmhurst Hospital Center, Forest Hills, New York, United States
  • Yaphe, Sean, Elmhurst Hospital Center, Forest Hills, New York, United States
  • Depa, Jayaramakrishna, Elmhurst Hospital Center, Forest Hills, New York, United States
  • Lee, Scott, Elmhurst Hospital Center, Forest Hills, New York, United States
Background

In trauma, the systemic inflammatory response and intensive care therapy leads to a hypermetabolic state described as Augmented Renal Clearance (ARC). Literature has shown an association between ARC and sub-therapeutic antibiotic concentrations and suggests worst clinical outcomes. We examined whether hepatic clearance is also augmented in trauma by measuring Dilantin levels (DL), a drug primarily metabolized by the liver.

Methods

A retrospective review of the trauma registry at our level 1 trauma center was conducted from 2009 to 2014 for adults admitted for traumatic brain injury receiving Dilantin. Patients with acute kidney injury were excluded. GFR was estimated using CKD-Epi formula. DL were corrected for hypoalbuminemia (<3 g/dL) and compared between ARC patients (eGFR > 130) and those without (nARC) at 24, 48 hours, and 72 hours.

Results

There were a total of 98 nARC (eGFR= 97.4) and 20 ARC patients (eGFR=133.3) all of which dosed similarly. ARC patients were younger, had lower creatinine and DL at 72 hours. At 48 and 72 hours the correlation comparing eGFR to DL is negative (p<.05). At 48 hours ALT levels were significantly higher (p<0.05).

Conclusion

ARC patients had lower DL at 24 and 48 hours, and DL correlated negatively with GFR augmentation. ALT and AST levels were higher in the ARC patients possibly due to increased hepatic function. In ARC, hepatic clearance may also be augmented raising issues of drug dosing regardless of renal or hepatic metabolism.

Descriptive statistics comparing ARC vs non-ARC patients
 non-ARC (n-=98)ARC (n=20) 
 meanmeanP-value
Age53.4530.2<0.001
Creatinine at 48 hours0.860.63<0.001
Dilantin level at 72 hours12.249.320.007
GFR on admission89.93125.40<0.001
GFR at 24 hours94.54134.10<0.001
GFR at 48 hours97.94133.30<0.001
Average GFR94.01130.94<0.001
ALT at 48 hours23.3538.92<0.05