Abstract: TH-PO282

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

Session Information

Category: Acute Kidney Injury

  • 001 AKI: Basic


  • Street, Jonathan, NIDDK, Bethesda, Maryland, United States
  • Bellomo, Tiffany Rose, NIDDK, Bethesda, Maryland, United States
  • Koritzinsky, Erik H., NIDDK, Bethesda, Maryland, United States
  • Kojima, Hiroshi, NIDDK, Bethesda, Maryland, United States
  • Chawla, Lakhmir S., George Washington University, San Diego, California, United States
  • Yuen, Peter S.T., NIDDK, Bethesda, Maryland, United States
  • Star, Robert A., NIDDK, Bethesda, Maryland, United States

The furosemide stress test (FST) measures urine production (diuresis) after a furosemide bolus. FST is a sensitive and specific predictor of a need for renal replacement therapy and mortality in the ICU. Furosemide causes a diuresis via 2 steps: 1) active secretion into the proximal tubule lumen, then 2) inhibition of thick ascending limb NKCC2. We hypothesize that tubule damage should reduce furosemide excretion (FEST) and prevent a subsequent increase in urine volume (FST). We developed FST and FEST protocols for a septic mouse model in which mortality is poorly predicted by filtration markers, and also tested the predictive performance of FEST in a human cohort.


We developed a sensitive reverse phase HPLC assay for urine furosemide. Male CD-1 mice underwent cecal ligation and puncture (CLP) to induce sepsis. 42 hrs post-CLP 1 mg/kg furosemide was given s.c. and urine was collected for the next 12 hrs to allow for intermittent urination. The mice were monitored every 8 hrs and euthanized if their clinical score exceeded the protocol threshold. Furosemide concentration was also measured in the post-furosemide challenge samples of 49 patients from the PASSKI cohort.


A moderate severity of CLP injury was used; 32 mice survived to 42 hr and underwent FST/FEST, 19 mice survived 7 d. Urine production during 12 hr varied from 0.08 to 2.62 ml. Both urine production and the fraction of furosemide recovered in the urine predicted mortality [AUC ROC values of 0.92 (p<0.0001) for FST and 0.87 (p<0.001) for FEST]. In the human cohort, the fraction of furosemide recovered predicted progression to AKIN stage III and was comparable to FST [AUC ROC values of 0.864 for FST and 0.848 for FEST].


The furosemide excretion stress test and furosemide stress test strongly predict post-sepsis mortality in mice, allowing for early stratification by severity in future drug studies of late treatment or enhancing recovery. FEST performs comparably to FST in the human PASSKI cohort.


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