Urinary Metabolomic Analysis for the Identification of Renal Injury in Patients With Acute Heart Failure

Abstract

Worsening renal function in patients admitted with heart failure is associated with increased morbidity. These changes are not usually apparent initially and often take up to 48 hours to be detected. Using the novel technique of metabolomic analysis, this study aims to determine if markers of renal injury are identifiable at presentation that are associated with the development of worsening renal function in high-risk patients with heart failure. A prospective exploratory study enrolled a convenience sample of patients with suspected heart failure. Eligible patients had to be older than 18 years, have a B-type natriuretic peptide (BNP) level over 100 pg/mL, have a history of diabetes or hypertension, meet Boston criteria for heart failure (>8), and require hospital admission as judged by the treating physician. Patients receiving no more than one dose of diuretic prior to enrollment were excluded. Urine was collected during the emergency department (ED) stay. Initial creatinine and the peak value between 24 to 48 hours were used to determine worsening renal function as defined by a change of >0.3 mg/dL or absolute 25% increase. Urine samples underwent gas chromatography/mass spectrometry (GC/MS) profiling. Peak metabolite values were measured and data were log-transformed. Partial least squares-discriminant analysis (PLS-DA) was used to identify metabolites associated with worsening renal function. Specific urinary metabolites were ranked based on their regression coefficients. The 24 enrolled subjects had a median age of 58 years (interquartile range [IQR] = 49.5 to 67.5 years) with 58% being male. Worsening renal function occurred in 10 subjects (41.7%). A total of 156 metabolites were identified. The optimal number of metabolites for class discrimination as determined by PLS-DA was three, with a classification accuracy of 78%. These metabolites were taurine, sulfuric acid, and talose. Urinary metabolites found at the time of presentation may be markers of early renal injury. It is therefore possible that the process of renal injury is initiated prior to ED arrival in patients with suspected heart failure, and these may be used to identify a high-risk patient population.