Urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 as biomarkers of patients with established acute kidney injury

Abstract

Background/Aims: Urinary tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) have been recently discovered and validated as sensitive biomarkers that can predict stage 2 or 3 acute kidney injury (AKI) development in high-risk patients. We aimed to assess whether these biomarkers could predict adverse outcomes and renal recovery in established AKI patients. Methods: This was a single-center study prospectively enrolling 124 patients diagnosed with AKI. TIMP-2, IGFBP7, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule 1 (KIM-1) levels were measured at the time of diagnosis and the predictive performance of short-term outcomes and renal recovery was assessed. Results: Patients were divided into 4 quartiles according to the initial urinary TIMP-2/IGFBP7 levels. Stage 3 AKI (odds ratio [OR], 17.86), classified by the Kidney Disease Improving Global Outcomes (KDIGO), as well as the third and fourth quartiles of TIMP-2/IGFBP7 (OR, 5.75 and 44.98, respectively), were found to be independent predictors of renal replacement therapy at the time of AKI diagnosis. In addition, KDIGO stage 3 AKI (OR, 2.468) or the third of fourth quartiles of urinary TIMP-2/IGFBP7 (OR, 1.896 and 3.622, respectively) were also found to be useful in predicting nonrecovery of renal function. In a separate analysis of patients with renal recovery at discharge, initial urinary TIMP-2/IGFBP7 or urinary IGFBP7 at discharge could also predict new-onset or progressive chronic kidney disease (CKD). Conclusions: In AKI patients, urine TIMP-2/IGFBP7 could serve as a biomarker for predicting adverse outcomes, renal recovery, or the development and progression of CKD.