Furosemide Stress Test and Biomarkers for the Prediction of AKI Severity

• Published in: Journal of the American Society of Nephrology Vol. 26; no. 8; pp. 2023 - 2031
• Main Authors: Koyner, Jay L, Davison, Danielle L, Brasha-Mitchell, Ermira, Chalikonda, Divya M, Arthur, John M, Shaw, Andrew D, Tumlin, James A, Trevino, Sharon A, Bennett, Michael R, Kimmel, Paul L, Seneff, Michael G, Chawla, Lakhmir S
• Format: Journal Article
• Language: English
• Published: United States American Society of Nephrology 01.08.2015
• Subjects: Acute Kidney Injury - blood; Acute Kidney Injury - mortality; Acute Kidney Injury - urine; Acute-Phase Proteins - urine; Aged; Albuminuria - urine; Biomarkers - blood; Biomarkers - urine; Clinical Research; Creatinine - urine; Disease Progression; Diuretics; Female; Furosemide; Hepatitis A Virus Cellular Receptor 1; Humans; Insulin-Like Growth Factor Binding Proteins - urine; Interleukin-18 - urine; Lipocalin-2; Lipocalins - blood; Lipocalins - urine; Male; Membrane Glycoproteins - urine; Middle Aged; Proto-Oncogene Proteins - blood; Proto-Oncogene Proteins - urine; Receptors, Virus; Severity of Illness Index; Sodium - blood; Sodium - urine; Tissue Inhibitor of Metalloproteinase-2 - urine; Uromodulin - urine; clinical nephrology; diuretics; acute renal failure
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/asn.2014060535

Clinicians have access to limited tools that predict which patients with early AKI will progress to more severe stages. In early AKI, urine output after a furosemide stress test (FST), which involves intravenous administration of furosemide (1.0 or 1.5 mg/kg), can predict the development of stage 3 AKI. We measured several AKI biomarkers in our previously published cohort of 77 patients with early AKI who received an FST and evaluated the ability of FST urine output and biomarkers to predict the development of stage 3 AKI (n=25 [32.5%]), receipt of RRT (n=11 [14.2%]), or inpatient mortality (n=16 [20.7%]). With an area under the curve (AUC)±SEM of 0.87±0.09 (P<0.0001), 2-hour urine output after FST was significantly better than each urinary biomarker tested in predicting progression to stage 3 (P<0.05). FST urine output was the only biomarker to significantly predict RRT (0.86±0.08; P=0.001). Regardless of the end point, combining FST urine output with individual biomarkers using logistic regression did not significantly improve risk stratification (ΔAUC, P>0.10 for all). When FST urine output was assessed in patients with increased biomarker levels, the AUC for progression to stage 3 improved to 0.90±0.06 and the AUC for receipt of RRT improved to 0.91±0.08. Overall, in the setting of early AKI, FST urine output outperformed biochemical biomarkers for prediction of progressive AKI, need for RRT, and inpatient mortality. Using a FST in patients with increased biomarker levels improves risk stratification, although further research is needed.