The Product of Tissue Inhibitor of Metalloproteinase (TIMP2) and Insulin Like Growth Factor Binding Protein 7 (IGFBP7) is Elevated at Baseline in Ambulatory Cancer Patients Prescribed Cisplatin

Identifying acute kidney injury (AKI) early in patients receiving cisplatin is problematic due to a lack of sensitive indicators and inherent delay in detection imposed by traditional biomarkers such as serum creatinine. In order to prevent, limit, and manage AKI, clinicians need sensitive and specific methods to detect toxicity in a timely manner after cisplatin therapy so that interventions can be readily implemented. The purpose of this pilot study was to describe urinary concentrations of the tissue inhibitor of metalloproteinase 2 (TIMP2) and insulin like growth factor binding protein 7 (IGFBP7) proteins, either alone or in combination in ambulatory cancer patients at baseline and after receiving cisplatin and evaluate receiver operating characteristic (ROC) curves for predicting exposures and AKI risks. Urinary TIMP2, IGFBP7, and TIMP2*IGFBP7 product analyses failed to demonstrate any statistically significant changes from baseline to follow-up at either day 3 or day 10 post cisplatin. At baseline, 91% of ambulatory cancer patients receiving cisplatin had a TIMP2*IGFBP7 product of 43.2 (ng/ mL)2/1000, which was greater than in previous reports. ROC curves failed to demonstrate significant utility of TIMP2, IGFBP7, or TIMP2*IGFBP7 at day 3 and day 10 for predicting exposures. ROC curves for the combination of TIMP2*IGFBP7 (absolute and urinary creatinine normalized) in predicting decreases in kidney function by estimated glomerular filtration rate (eGFR) demonstrated good to excellent utility with values of 0.80 to 0.92. While the current study cannot support adoption of the AKI predictive value of > 0.3 for TIMP2*IGFBP7, changes in eGFR can be reasonably predicted in ambulatory cancer patients receiving cisplatin. Additional studies will be needed to determine the applicability of cut-points for cisplatin AKI predictions.