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Abstract: SA-PO076

Worsening Renal Function During Aggressive Diuresis Is Not Due to Kidney Injury in Acute Heart Failure Patients

Session Information

Category: Acute Kidney Injury

  • 003 AKI: Clinical and Translational


  • Rein, Joshua L., Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Jackson, Keyanna, Yale University, New Haven, Connecticut, United States
  • Rao, Veena, Yale University, New Haven, Connecticut, United States
  • Coca, Steven G., Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Testani, Jeffrey M., Yale University, New Haven, Connecticut, United States

The mechanisms underlying worsening renal function (WRF) in the setting of aggressive diuresis for acute heart failure (AHF) treatment may reflect renal tubular injury or simply indicate a hemodynamic or functional change in glomerular filtration. Well-validated tubular injury biomarkers—NAG, NGAL, and KIM-1— are now available that can quantify the degree of renal tubular injury. The ROSE trial provides an ideal experimental platform for the study of mechanisms of WRF during aggressive diuresis for AHF as the ROSE protocol dictated high dose loop diuretic therapy in all patients. We sought to determine whether kidney injury is a predominant mechanism for WRF in the setting of aggressive diuresis and its impact on prognosis.


Patients in the multicenter ROSE trial with baseline and 72-hour urine injury biomarkers were analyzed (N=277). WRF was defined as a ≥20% decrease in glomerular filtration rate estimated using cystatin C.


Levels of NAG and KIM-1 did not change with aggressive diuresis (P>0.49, both), whereas levels of NGAL decreased slightly [-8.0 ng/mg (-169, 35 ng/mg), P<0.001]. WRF occurred in 21.7% of the population and was not associated with an increase in any marker of renal injury: NGAL (P=0.23), NAG (P=0.49), or KIM-1 (P=0.22). WRF was not associated with reduced survival (P=0.51). However, increases in NGAL, NAG, and KIM-1 were paradoxically associated with improved survival (adjusted HR: 0.78 per 10 percentile increase, 95% CI: 0.69-0.91; P=0.001). Change in injury biomarkers could not differentiate high versus low risk forms of WRF (Pinteraction=0.35).


Renal injury was not a dominant mechanism for WRF in the context of aggressive diuresis of ADHF patients. Moreover, neither WRF nor renal injury was associated with an increased risk of death. These findings reinforce the notion that small to moderate “bumps” in creatinine commonly encountered with aggressive diuresis are mechanistically and prognostically different from traditional causes of acute kidney injury.

Baseline and 72 hour Biomarkers of Tubular Injury According to WRF Status.