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

Abstract

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.

Biomarkers of Drug-Induced Kidney Toxicity

“…However, in another study, urinary [TIMP2] x [IGFBP7] was found to be a useful tool for early identification of patients who are at risk for cisplatin-induced AKI. 142 In this study, urine samples were collected before cisplatin injection and 12 hours after the end of chemotherapy. Four patients out of 58 developed AKI within 72 hours.…”

Urinary protein biomarkers of kidney injury in patients receiving cisplatin chemotherapy

“…The intended use of NephroCheckV R is for the clinical risk assessment for moderate to severe AKI within the next 12 h specifically in ICU patients (at least 21 years of age) who have or have had acute cardiovascular and/or respiratory compromise within the past 24 h. There has been interest in assessing the utility of NephroCheckV R for other causes of AKI including drug-induced toxicity. In one clinical study, 4 of 32 patients receiving cisplatin developed AKI, and the AUC-ROC value for TIMP2ÂIGFBP7 was 0.92 within 72 h. 73 However, another study that measured the two biomarkers individually found that there was no change in IGFBP7 concentrations 24 h after cisplatin administration, whereas a 1.1-fold increase in TIMP2 levels could be observed. 71 While 13 patients developed AKI in this study, the AUC-ROC value for the product of TIMP2ÂIGFBP7 was only 0.46 at 24 h. A third study of 46 patients also showed no significant changes from baseline for either TIMP2 or IGFBP7 as well as for TIMP2ÂIGFBP7 at days 3 and 10 after cisplatin treatment.…”

(TIMP2) x (IGFBP7) as early renal biomarker for the prediction of acute kidney injury in aortic surgery (TIGER). A single center observational study

“…Others have previously tested TIMP2xIGFBP7 in a variety of pathologies leading to AKI including e.g. cardiac surgery, major non-cardiac surgery, transcatheter aortic valve implantation (TAVI), critical illness, heart failure and platinum-based chemotherapy and have showed rather consistent results [ 17 , 18 , 20 , 22 , 23 , 32 ]. Thus, current recommendations suggest (TIMP-2) x (IGFBP7) testing in different patient cohorts irrespective of po-AKI-etiology [ 16 ], as performed in this study.…”