Glomerular Filtration Rate Is a Confounder for the Measurement of Soluble Mesothelin in Serum

Abstract

The mesothelin gene encodes a 71-kDa precursor protein that is subsequently cleaved into a soluble megakaryocyte potentiating factor and a membrane-bound part, mesothelin. Mesothelin can be shed as “soluble mesothelin” or “soluble mesothelin-related protein” (SMRP),1 which is an approximately 40-kDa biomarker of malignant mesothelioma, an asbestos-related cancer (1). Mesothelioma typically occurs in middle-aged men, and the renal function or the glomerular filtration rate (GFR) can occasionally decrease in these patients and in individuals at risk of developing mesothelioma. Renal impairment leads to the accumulation of low molecular weight proteins in the blood [e.g., cystatin C (13 kDa) and β-trace protein (BTP) (23–29 kDa)], and these proteins have been used as markers of the GFR. Such renal impairment can also cause the accumulation of soluble mesothelin, as has previously been reported for a limited number of cases(2). Our aim, therefore, was to thoroughly investigate the impact of renal function on serum SMRP concentrations. We enrolled 66 individuals (49 men and 17 women; median age, 58 years; range, 24–80 years), who were referred for measurement of 51Cr-EDTA clearance to estimate the GFR. We excluded patients with asbestos-related diseases/malignancies, patients with endometrial, ovarian, cervix, lung, breast, pancreatic, or gastrointestinal cancer, and patients with leukemia, because these conditions can overexpress mesothelin (3)(4). The study was approved by the ethics committee of both participating hospitals, and participants gave written informed consent. …