Abstract: SA-PO139
A Furosemide Excretion Stress Test (FEST) Predicts Mortality After Sepsis Independent of Vasopressin Administration
Session Information
- AKI: Mechanisms - AKI-CKD Transition
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 102 AKI: Clinical, Outcomes, and Trials
Authors
- Street, Jonathan, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States
- Bellomo, Tiffany Rose, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States
- Koritzinsky, Erik H., National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States
- Kojima, Hiroshi, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States
- Yuen, Peter S.T., National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States
- Star, Robert A., National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States
Background
The furosemide stress test (FST) has been shown to be a sensitive and specific predictor of progression to AKIN stage III in the ICU. FST measures the volume of urine produced after a furosemide bolus. Furosemide is actively excreted by the proximal tubules into the lumen where it inhibits NKCC2 in the thick ascending limb. Vasopressin is used as a vasopressor in some hypotensive sepsis patients and can markedly reduce urine production. We hypothesize that furosemide excretion (FEST) will be a more direct measure of tubule health than diuresis (FST) and may be insensitive to the effects of vasopressin on urine volume. We developed a protocol for FST and FEST in mice and tested this hypothesis in a murine model of septic-AKI.
Methods
Sepsis was induced in male and female CD-1 mice by cecal ligation and puncture (CLP). A subgroup of mice received 0.00114 U/(kg.min) vasopressin i.p. to simulate vasopressor support. The FST/FEST started at 42 hours post-CLP. 1 mg/kg furosemide s.c. was given and urine collected for 12 hours. The mice were monitored until 7 days post-CLP. Furosemide concentration was determined by a reverse phase HPLC assay.
Results
From 139 mice (79M/60F), 55 survived to 42 hours and underwent FST/FEST with 33 mice surviving to 7 days. Both FST and FEST predicted time of death (R2 = 0.26 and 0.74) and mortality [AUC ROC values of 0.92 for FST in males, 0.95 for FST in females, 0.87 for FEST for males, and 1.00 for FEST in females]. Optimal performance was 91% sensitivity and 82% specificity for FST and 90%/79% for FEST with cutoffs of 0.94 ml and 44%, respectively. In the subgroup receiving vasopressin, urine production was reduced by 0.6 ml (p = 0.03) without altering furosemide excretion (p = n.s.). Therefore, when we used the optimal cutoffs from septic mice not treated with vasopressin for vasopressin-treated septic mice, the specificity of FST was eliminated (0%, p < 0.01) but specificity of FEST was preserved.
Conclusion
The FST and FEST perform similarly in predicting mortality in untreated animals. Only the furosemide excretion stress test also predicted time to death and was insensitive to vasopressin treatment. In order to use FST in conjunction with vasopressin, cutoff values must be adjusted, but such adjustment is not needed for FEST.
Funding
- NIDDK Support