Worsening Renal Function in Acute Heart Failure Patients Undergoing Aggressive Diuresis is Not Associated with Tubular Injury

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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 tubularinjury. The ROSE-AHF trial provides an experimental platform for the study of mechanisms of WRF during aggressive diuresis for AHF, as the ROSE-AHF protocol dictated high dose loop diuretic therapy in all patients. We sought to determine whether tubular injury biomarkers are associated with WRF in the setting of aggressive diuresis and its association with prognosis.


Patients in the multicenter ROSE-AHF trial with baseline and 72-hour urine tubular injury biomarkers were analyzed (N=283). WRF was defined as a ≥20% decrease in glomerular filtration rate estimated using cystatin C.


Consistent with protocol driven aggressive dosing of loop diuretics, participants received a median 560 mg of IV furosemide equivalents (IQR 300-815 mg) which induced a urine output of 8425 mL (IQR 6341-10528 ml) over the 72-hour intervention period. Levels of NAG and KIM-1 did not change with aggressive diuresis (P>0.59, both), whereas levels of NGAL decreased slightly [-8.7 ng/mg (-169, 35 ng/mg), P<0.001]. WRF occurred in 21.2% of the population and was not associated with an increase in any marker of renal tubular injury: NGAL (P=0.21), NAG (P=0.46), or KIM-1 (P=0.22). Increases in NGAL, NAG, and KIM-1 were paradoxically associated with improved survival (adjusted HR: 0.80 per 10 percentile increase, 95% CI: 0.69-0.91; P=0.001).


Kidney tubular injury does not appear to have an association with WRF in the context of aggressive diuresis of AHF patients. These findings reinforce the notion that the small to moderate deteriorations in renal function commonly encountered with aggressive diuresis are dissimilar from traditional causes of acute kidney injury.

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