Urinary [TIMP‐2] × [IGFBP7] for risk prediction of acute kidney injury in decompensated heart failure

Abstract

Background In acute decompensated heart failure (ADHF) the risk of acute kidney injury (AKI) is high. Early detection of patients at risk for AKI is important. We tested urinary [TIMP‐2] × [IGFBP7], a new US Food and Drug Administration–cleared test to assess AKI risk, in a cohort of hospitalized ADHF patients. Hypothesis In patients with ADHF, urinary [TIMP‐2] × [IGFBP7] is associated with moderate to severe AKI and related to increased mortality. Methods We enrolled 400 patients in the emergency department at Robert‐Bosch Hospital, Stuttgart, Germany. We examined the predictive ability of urinary [TIMP‐2] × [IGFBP7] (units: [ng/mL]2/1000) for development of AKI stage 2 or 3 within 24 hours of sample collection in patients with ADHF. Operating characteristics were determined for the validated cutoffs of 0.3 and 2.0. Results Forty patients had ADHF upon presentation and sufficient data for AKI staging. 27.5% developed AKI stage 2–3 within 7 days. Urinary [TIMP‐2] × [IGFBP7] discriminated for AKI stage 2–3 over the first day with an area under the ROC curve of 0.84 (95% confidence interval: 0.72‐0.93) and over 7 days with an AUC of 0.77 (95% confidence interval: 0.65‐0.88). For the first day, sensitivity was 86% at the 0.3 cutoff and specificity was 95% at the 2.0 cutoff for prediction of AKI stage 2–3. There was a trend (P = 0.08) for higher mortality in patients with urinary [TIMP‐2] × [IGFBP7] >2.0 and AKI 2–3. Conclusions Urinary [TIMP‐2] × [IGFBP7] is a promising marker for AKI risk assessment in patients with ADHF.

Serum Cystatin C Predicts AKI and the Prognosis of Patients in Coronary Care Unit: a Prospective, Observational Study

“…Nevertheless, in patients with ADHF, Yang et al have shown that the incidence of AKI further increased to 47.6%[30]. This higher incidence of AKI in ADHF patients has been referred to as acute cardiac and renal dysfunction [31-34]. …”

Novel heart failure biomarkers: why do we fail to exploit their potential?

“…Further investigations will be needed to establish this association with HFpEF. Urinary IGFBP-7 levels are, together with tissue inhibitor of metalloproteinase 2 (TIMP-2), predictive for acute kidney injury in decompensated HF and post-coronary artery bypass surgery [92][93][94][95]. Thus, in addition to being a plasma biomarker, levels in other body fluids such as urine can provide diagnostic and/or prognostic information about patients.…”

Comparison of Prognostic Usefulness of Serum Insulin-Like Growth Factor-Binding Protein 7 in Patients With Heart Failure and Preserved Versus Reduced Left Ventricular Ejection Fraction

“…, which to some extent may be associated with the increased IGFBP-7, however when adjusted for these parameters the difference between the 2 HF groups remained statistically significant. Urinary IGFBP-7, along with TIMP-2, has in acute decompensated HF been suggested as a cell cycle arrest marker indicative of acute kidney injury(21). Cell cycle arrest is believed to be a protective mechanism initiated in the earliest stages of tubule cell stress/injury in response to insults, such as inflammation and oxidative stress, shutting down cell processes thereby protecting the cell from permanent damage or death.…”