Acute Tubular Injury is Not a Major Mechanism for Worsening Renal Function in Patients Treated for Acute Heart Failure

Abstract

Introduction: Worsening Renal Function (WRF) often complicates decongestion of patients with Acute Heart Failure (AHF). The mechanisms of WRF in these patients remain unclear as it may reflect renal tubular injury or simply represent a hemodynamic or functional change in renal filtration. Validated biomarkers-NAG, NGAL, and KIM-1-are available that can detect and quantify the degree of renal tubular injury In the ROSE-AHF trial patients underwent very aggressive loop diuretic administration (2.5 times home dose; placebo group made 8.3L of urine) thus providing the optimal vehicle to evaluate the mechanism of aggressive diuresis induced WRF. Hypothesis: If renal injury is a predominant mechanism in diuresis induced WRF, then levels of kidney injury biomarkers should increase with WRF. Furthermore, injury biomarkers may assist in phenotyping the mechanism and thus outcomes associated with WRF Methods: Aggressively diuresed patients in the ROSE-AHF trial with baseline and 72-hour urinary NGAL, NAG, KIM-1, and plasma cystatin C were analyzed (N= 277). WRF was defined as a ≥20% decrease in estimated glomerular filtration rate (eGFR). Results: The median dose of furosemide (or equivalents) received through the 72-hour intervention period was 559 mg (IQR 300-803), which was similar in patients with (N= 60) and without (N= 217) WRF (P=.22). There were no significant differences in the change in NGAL (P =.23), NAG (P =.49), or KIM-1 (P =.22) between those with or without WRF (Fig. 1). WRF was not associated with reduced 6-month survival (HR = 0.80, 95% CI 0.41-1.5, P=.51) in this aggressively diuresed cohort. Similarly, increases in NGAL, NAG, and KIM-1 were not associated with worsened survival (P =.69, Fig. 2). Elevations in injury biomarkers were unable to identify a higher risk form of WRF (Pinteraction = 0.47). Conclusion: Acute tubular injury was not a dominant mechanism behind WRF during aggressive diuresis of hospitalized AHF patients. Moreover, in this setting, neither WRF nor evidence of renal tubular injury appeared to have a negative impact on mortality. These findings challenge traditionally held clinical connotations of WRF during treatment of AHF.