Targeting the Kidney in Acute Heart Failure: Can Old Drugs Provide New Benefit?

Abstract

Acute decompensated heart failure (ADHF) is the most common cause of hospital admission in persons aged >65 years, accounting for 1 000 000 admissions and >6 million hospital days.1 The total cost of HF care in the United States is currently estimated at $21 billion and is projected to increase to $53 billion in 2030 with the majority of costs (80%) related to ADHF hospitalizations.2 The prognosis of patients admitted with ADHF is dismal, with a 20% to 30% readmission rate and a 20% to 30% mortality rate within 6 months after admission.3 Studies have established the prognostic importance of renal function in patients with HF. Analysis from the second prospective randomized study of Ibopamine on mortality and efficacy4 was one of the first to demonstrate that estimated glomerular filtration rate (GFR) was the strongest predictor of mortality in ADHF. In the ADHF national registry (ADHERE), 63% of patients with ADHF had moderate renal dysfunction (GFR<60 mL/min m2) on admission and in-hospital mortality was strongly associated with the severity of renal dysfunction.5 A meta-analysis of 16 studies characterizing the association between renal impairment and mortality in patients with HF indicated that 1-year mortality increased incrementally across the range of renal function with a 7% increase in risk for every 10 mL/min decrease in GFR.6 As recently reviewed,7 numerous more recent studies have confirmed the association of renal dysfunction with adverse short- and long-term outcomes in ADHF, an association which seems equally robust in patients with ADHF with reduced or preserved ejection fraction. In patients hospitalized with ADHF, several studies demonstrated that acute kidney injury (AKI) during treatment of ADHF is common, with increases in creatinine ≥0.3 mg/dL occurring in 25% to 30% of patients. Regardless of baseline renal function, AKI is associated …