Urinary TIMP2·IGFBP7 for the prediction of platinum-induced acute renal injury

Abstract

Moritz Schanz,1 Anette Hoferer,2 Jing Shi,3 Mark Dominik Alscher,1 Martin Kimmel1 1Division of General Internal Medicine and Nephrology, Department of Internal Medicine, 2Division of Oncology, Department of Internal Medicine, Robert-Bosch Hospital, Stuttgart, Germany; 3Walker Bioscience, Carlsbad, CA, USA Introduction: Platinum-based chemotherapy (PBC) is a potent antineoplastic treatment, but cisplatin nephrotoxicity is often the limiting factor. Identifying the patients who are at risk for developing platinum-induced renal injury is an important issue. We tested urinary TIMP2·IGFBP7, a new US Food and Drug Administration (FDA)-cleared test to assess the risk of acute kidney injury (AKI), in a cohort of patients with malignant neoplastic disease receiving PBC.Patients and methods: A total of 58 patients with malignant neoplastic disease were enrolled in this study, of whom 32 patients had both urine samples and subsequent serum creatinine values available for detecting AKI within 72 hours. Urine samples were collected within 6 hours prior to PBC application and within 12 hours after the end of chemotherapy administration. We examined the predictive ability of TIMP2·IGFBP7 for the development of AKI as defined by KDIGO (Kidney Disease: Improving Global Outcomes) criteria within 72 hours after the administration of chemotherapy. Operating characteristics were determined for the previously validated TIMP2·IGFBP7 cutoff of 0.3 (ng/mL)2/1000.Results: Four (12.5%) patients developed AKI within 72 hours. Primary disease was lymphoma in 13 patients (40.6%) and solid tumors in 19 patients (59.4%). Eight patients (25.0%) received carboplatin and 24 (75.0%) cisplatin. TIMP2·IGFBP7 after PBC administration discriminated for the risk of AKI with an area under the receiver operating characteristic curve (AUC; 95% confidence interval) of 0.92 (0.80–1.00). At the cutoff of 0.3 for TIMP2·IGFBP7, sensitivity was 50%, specificity was 87%, negative predictive value was 95% and positive predictive value was 25% for the prediction of AKI within 72 hours.Conclusion: Urinary TIMP2·IGFBP7 measured in specimens gathered after PBC may be a useful tool to early identify patients who are at risk for developing platinum-induced AKI. Keywords: acute kidney injury, biomarker, cisplatin, nephrotoxicity, insulin like-growth factor binding protein-7, tissue inhibitor of metalloproteinases-2

Keywords

• acute kidney injury
• biomarker
• cisplatin nephrotoxicity
• insulin like-growth factor binding protein-7
• tissue inhibitor of metalloproteinases-2