False-Positive Elevation of Creatine Kinase MB Mass Concentrations Caused by Macromolecules in a Patient who Underwent Nephrectomy for Renal Cell Carcinoma

Creatine kinase MB isoform (CK-MB) is a biochemical marker that is used to evaluate patients with suspected acute myocardial infarction. Rapid immunoassays to measure CK-MB mass concentration use various monoclonal anti-CK-MB antibodies, and these have been reported to be highly sensitive, specific, and free of interference [1]. Here, we report the first case of a false-positive CK-MB result (as determined by a mass assay) from a patient who underwent nephrectomy for renal cell carcinoma. A 78-yr-old man was admitted to the Urology department of Ilsan Paik Hospital in Goyang, Korea, for partial nephrectomy for the treatment of renal cell carcinoma. He developed dyspnea and tachycardia at three days after the surgery. The electrocardiogram revealed atrial fibrillation. CK-MB mass concentrations, CK activity, and N-terminal B-type natriuretic peptide (NT-pro-BNP) levels increased to 10.44 μg/L (reference range, <6.8 μg/L), 1,533 U/L (<171 U/L), and 15,927 ng/L (526 ng/L), respectively. However, the troponin I level was normal (Fig. 1). Acute myocardial infarction was suspected because CK-MB mass concentrations were increased; however, the results of the transthoracic echocardiogram and cardiac angiography were unremarkable. During the week following admission, the patient’s CK-MB mass concentration using CK-MB VIDAS test (Vidas-Biomerieux, Marcy-I’Etoile, France) increased to more than 300 μg/L. With sample dilutions, the results were not linear. Following heterophilic blocking tube (HBT) (Scantibodies Laboratory, Santee, CA, USA) treatment, no changes in CK-MB mass concentrations were observed. With Elecsys Creatine Kinase MB reagent (Roche Diagnostics, GmbH, Mannheim, Germany), the CK-MB mass concentration was found to be 6 μg/L (reference range, <6.73 μg/L). CK electrophoresis with a SPIFE CK Vis Isoenzyme Kit (Helena Laboratories, Beaumont, TX, USA) revealed only a creatine kinase MM isoform (CK-MM) band. 98.3% of the CK-MB mass concentration was decreased by polyethylene glycol (PEG) precipitation [2]. These results raised the possibility of the presence of macro-CK. Macromolecules have been reported to have little to no influence on CK-MB mass assays [3]. Mass assays have previously been reported to be an effective method to exclude macro-CK interference in a CK-MB activity assay [4, 5]. However, our case demonstrated that macromolecules could falsely elevate CK-MB mass concentration, persisting for a minimum of four weeks. It is particularly important to distinguish macro-CK from CKMB to avoid unnecessary invasive procedures in patients with symptoms mimicking acute coronary syndrome. Our patient underwent relatively expensive and invasive procedures such as