Mesothelin levels in urine are affected by glomerular leakage and tubular reabsorption

Abstract

Background: Mesothelin is a soluble biomarker of malignant mesothelioma. Levels in serum, however, are also influenced by other factors, including age and glomerular filtration rate (GFR). The measurement of mesothelin in urine has recently gained interest, but the renal handling of this protein has not been sufficiently examined.

Patients and methods: A total of 75 patients with benign kidney disease were prospectively included in the study. Mesothelin levels were measured in the serum and in the urine of all the participants by using enzyme-linked immunosorbent assay. Urinary albumin and alpha 1-microglobulin (A1M) levels, which are markers of glomerular leakage and of decreased tubular reabsorption, respectively, and the estimated GFR (eGFR) of each participant were obtained. All urine analyte levels were standardized (std) against urinary creatinine levels.

Results: Absolute mesothelin levels in urine (median, 0.58 nmol/L; interquartile range [IQR], 0.25-1.03 nmol/L) were significantly lower than those in serum (median, 1.74 nmol/L; IQR, 1.35-2.43 nmol/L; P < .001). Urinary mesothelin(std) levels positively correlated with serum mesothelin (r = 0.35, P < .01), albumin(std) (r = 0.51, P < .001), and A1M(std) levels (r = 0.71, P < .001). Neither age nor eGFR were associated with urinary mesothelin(std) levels. Similarly, multiple linear regression analysis indicated that only albumin(std) and A1M(std) levels were significantly positively associated with the urinary mesothelin(std) levels (adjusted R(2) = 0.49).

Conclusion: Mesothelin levels in urine are affected by impaired glomerular and tubular function, which can influence the interpretation of mesothelin measurements and might cause false-positive results. These effects need to be accounted for to improve the further validation and possible clinical use of urinary mesothelin.