Improvement in Renal Function During the Treatment of Acute Decompensated Heart Failure: Relationship With Markers of Renal Tubular Injury and Prognostic Importance

Background: Improvement in renal function (IRF) in acute decompensated heart failure is associated with adverse outcomes. The mechanisms driving this paradox remain undefined.

Methods: Using the ROSE-AHF study (Renal Optimization Strategies Evaluation-Acute Heart Failure), 277 patients were grouped according to renal function, with IRF defined by a ≥20% increase (N=75), worsening renal function by a ≥20% decline (N=53), and stable renal function (SRF) by a <20% change (N=149) in estimated glomerular filtration rate between baseline and 72 hours. Three well-validated renal tubular injury markers, NGAL (neutrophil gelatinase-associated lipocalin), NAG (N-acetyl-β-d-glucosaminidase), and KIM-1 (kidney injury molecule 1), were evaluated at baseline and 72 hours. Patients were also classified by the pattern of change in these markers.

Results: Patients with IRF had the lowest admission estimated glomerular filtration rate (IRF, 37 [28 to 51] mL/min per 1.73 m²; worsening renal function, 43 [35 to 55] mL/min per 1.73 m²; and SRF, 43 [32 to 55] mL/min per 1.73 m²; P_trend=0.032) but greater cumulative urine output (IRF, 8780 [7025 to 11 208] mL; worsening renal function, 7860 [5555 to 9765] mL; and SRF, 8150 [6325 to 10 456] mL; P_trend=0.024) and weight loss (IRF, -9.0 [-12.4 to -5.3] lb; worsening renal function, -5.1 [-8.1 to -1.3] lb; and SRF, -7.1 [-11.9 to -3.2] lb; P_trend<0.001) despite similar diuretic doses (P_trend=0.16). There were no differences in the relative change in NGAL, NAG, or KIM-1 between renal function groups (P_trend>0.19 for all). Patients with IRF had worse survival than patients with SRF (27% versus 54%; hazard ratio, 1.98 [1.10-3.58]; P=0.024).

Conclusions: IRF during decongestive therapy for acute decompensated heart failure was not associated with improved markers of renal tubular injury and was associated with worsened survival, likely driven by the presence of greater underlying cardiorenal dysfunction and more severe congestion.