Fractional excretion of urea nitrogen can identify true worsening renal function in patients with acute heart failure

Abstract

Abstract Background Worsening renal function (WRF) often occurs during decongestive treatment in acute heart failure (AHF). Although WRF has previously been associated with worse prognosis, recent studies have revealed that it may not contribute to an unfavorable outcome in the setting of adequate decongestion achieved. Therefore, there is growing interest to identify patients who develop "true WRF" with poor outcomes. Purpose Fractional excretion of urea nitrogen (FEUN), which is used to differentiate causes of renal failure, has emerged as a surrogate marker of volume status in patients with AHF complicated by renal dysfunction. Recent study has reported that a low FEUN value (FEUN ≤32.1%) represents intravascular dehydration, whereas a high FEUN value (FEUN >38.0%) reflects intravascular congestion, both being independent adverse prognostic factors. Therefore, we hypothesized that FEUN could identify "true WRF" in patients with AHF. Methods We examined 801 hospitalized patients with AHF and renal dysfunction (defined as discharge estimated glomerular filtration rate <60 mL/min/1.73 m²) whose FEUN was measured at discharge. The patients were divided into four groups as follows: no WRF (n=683); WRF with low FEUN (≤32.1%) (n=36); WRF with medium FEUN (>32.1% and ≤38.0%) (n=25); and WRF with high FEUN (>38.0%) (n=57). WRF was defined as an increase in serum creatinine ≥0.3 mg from admission to discharge. FEUN was calculated by the following formula: (urinary urea × serum creatinine) × 100 / (serum urea × urinary creatinine). The primary endpoint was the composite of all-cause death and heart failure (HF) readmission within 1-year after discharge. Results Regarding baseline characteristics, the WRF with low FEUN group had lower left ventricular ejection fraction, whereas the WRF with high FEUN group had poorer renal function. During the median follow-up period of 300 days, 18 all-cause deaths and 165 HF readmissions occurred. Kaplan–Meier analysis showed that patients without WRF had a significantly higher event-free survival rate than those with WRF. In addition, the WRF with medium FEUN group had a significantly higher event-free survival rate similar to that of the no WRF group, whereas the WRF with low FEUN and WRF with high FEUN groups had lower event-free survival rates. In multivariable Cox regression analysis, the WRF with low FEUN (hazard ratio, 1.91; 95% confidence interval, 1.02–3.57; P=0.043) and WRF with high FEUN (hazard ratio, 1.71; 95% confidence interval, 1.02–2.89; P=0.043) groups were independently associated with poor outcomes, even after adjusting for confounders. Conclusion Our study suggests that FEUN can identify prognostically relevant WRF and may be a useful marker for guiding decongestive therapy in patients with AHF complicated by WRF.Table 1Figure 1