Dataset Information

A Furosemide Excretion Stress Test Predicts Mortality in Mice After Sepsis and Outperforms the Furosemide Stress Test During Vasopressin Administration.

ABSTRACT:

Objectives

The furosemide stress test measures the volume of urine produced after a furosemide challenge. Furosemide stress test has previously demonstrated sensitive and specific prediction of progression to Kidney Disease: Improving Global Outcomes guideline defined acute kidney injury stage III in the ICU. Furosemide is actively excreted into the nephron lumen where it inhibits the sodium-potassium-chloride cotransporter, causing diuresis. We hypothesize that furosemide excretion is a more direct measure of tubule health than diuresis.

Design

We developed a furosemide excretion stress test to evaluate this hypothesis in a murine model of septic-acute kidney injury.

Setting

Basic science laboratory.

Subjects

Male and female 8-week old CD-1 mice.

Interventions

Sepsis was induced by cecal ligation and puncture in male and female mice. Furosemide stress test/furosemide excretion stress test started 42 hours post-cecal ligation and puncture with a 1 mg/kg furosemide bolus and urine was collected for 12 hours. The mice were then euthanized or monitored until 7 days post-cecal ligation and puncture. In another cohort, mice were treated with vasopressin, which decreases urine volume. Furosemide concentration was determined by high performance liquid chromatography.

Measurements and main results

Urine production during the 12-hour collection varied from 0.08 to 2.62 mL. Both urine production (furosemide stress test) and furosemide excretion (furosemide excretion stress test) predicted mortality (area under the receiver operating characteristic curve = 0.925 and 0.916) and time of death (R ² = 0.26 and 0.74). Male and female mice demonstrated consistent results. Following vasopressin treatment, furosemide stress test specificity fell to 33% (p = 0.016) but furosemide excretion stress test specificity was maintained.

Conclusions

The furosemide stress test and furosemide excretion stress test performed similarly in predicting mortality; however, furosemide excretion stress test was superior in predicting time to death and maintained performance when challenged with vasopressin treatment in a mouse sepsis model.

SUBMITTER: Street JM

PROVIDER: S-EPMC7259566 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Publications

A Furosemide Excretion Stress Test Predicts Mortality in Mice After Sepsis and Outperforms the Furosemide Stress Test During Vasopressin Administration.

Street Jonathan M JM Bellomo Tiffany R TR Koritzinsky Erik H EH Kojima Hiroshi H Yuen Peter S T PST Star Robert A RA

Critical care explorations 20200507 5

<h4>Objectives</h4>The furosemide stress test measures the volume of urine produced after a furosemide challenge. Furosemide stress test has previously demonstrated sensitive and specific prediction of progression to Kidney Disease: Improving Global Outcomes guideline defined acute kidney injury stage III in the ICU. Furosemide is actively excreted into the nephron lumen where it inhibits the sodium-potassium-chloride cotransporter, causing diuresis. We hypothesize that furosemide excretion is a ...[more]

PMID: 32671344

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Dataset Information

A Furosemide Excretion Stress Test Predicts Mortality in Mice After Sepsis and Outperforms the Furosemide Stress Test During Vasopressin Administration.

Objectives

Design

Setting

Subjects

Interventions

Measurements and main results

Conclusions

Publications

A Furosemide Excretion Stress Test Predicts Mortality in Mice After Sepsis and Outperforms the Furosemide Stress Test During Vasopressin Administration.

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