Kidney Week

Abstract: FR-PO022

A Furosemide Excretion Stress Test (FEST) Predicts AKI Progression and Mortality After Sepsis

Session Information

• AKI: Clinical, Outcomes, Trials - I
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 102 AKI: Clinical, Outcomes, and Trials

Authors

• Street, Jonathan, NIDDK/NIH, Bethesda, Maryland, United States

Jonathan Street,

• Bellomo, Tiffany Rose, NIDDK/NIH, Bethesda, Maryland, United States

Tiffany Rose Bellomo,

• Koritzinsky, Erik H., NIDDK/NIH, Bethesda, Maryland, United States

Erik H. Koritzinsky,

• Kojima, Hiroshi, NIDDK/NIH, Bethesda, Maryland, United States

Hiroshi Kojima,

• Chawla, Lakhmir S., University of California, San Diego, San Diego, California, United States

Lakhmir S. Chawla,

• Yuen, Peter S.T., NIDDK/NIH, Bethesda, Maryland, United States

Peter S.T. Yuen,

• Star, Robert A., NIDDK/NIH, Bethesda, Maryland, United States

Robert A. Star,

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. We hypothesize that furosemide excretion (FEST) will be a more direct measure of tubule health than diuresis (FST). We developed a protocol for FST and FEST in mice and tested this hypothesis in a murine model of septic-AKI and in a human cohort.

Methods

Sepsis was induced in male and female CD-1 mice by cecal ligation and puncture (CLP). 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 new reverse phase HPLC assay in the mouse urine samples and urine samples from 49 patients in the PASSKI cohort.

Results

In the mouse model a moderate severity of sepsis was used and similar mortality was seen in the males and females. In the male group, from 79 mice 32 survived to 42 hours and underwent FST/FEST with 19 mice surviving to 7 days compared to 60/23/14 in the females. Urine production during the 12 hour collection varied from 0.08 to 2.62 ml. Urine production post-challenge and the fraction of furosemide recovered predicted 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]. Both FST and FEST predicted time of death in males (R² = 0.30 and 0.75), males and females combined (R² = 0.26 and 0.74) but not females alone. FST and FEST correlated with kidney NKCC2 mRNA levels (R² = 0.35 and 0.46), and weakly with BUN, ALT and CK. In the human cohort, FST and FEST were comparable in predicting progression to KDIGO stage III (AUC ROC values of 0.864 for FST and 0.848 for FEST).

Conclusion

In both the mouse model and human cohort the furosemide stress test and furosemide excretion stress test perform similarly with FST slightly superior in predicting mortality or progression. The furosemide excretion stress test predicted time to death in the mouse model.

Funding

• NIDDK Support