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

Our plain-English summary of Mesothelin levels in urine are affected by glomerular leakage and tubular reabsorption, by K. Hollevoet, M.M. Speeckaert, A.S. Decavele, et al (Clinical Lung Cancer, 2012).

The study

• Authors: K. Hollevoet, M.M. Speeckaert, A.S. Decavele, R. Vanholder, J.P. van Meerbeeck, J.R. Delanghe
• Journal: Clinical Lung Cancer
• Published: 2012;13(6):470-4
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

Copyright © 2012 Elsevier Inc. All rights reserved.

In plain English

This study from Ghent University Hospital, Belgium, examined how the kidneys affect mesothelin levels in urine. The authors describe mesothelin as a soluble biomarker of malignant mesothelioma. Between November and December 2010, 75 patients with benign kidney disease were prospectively enrolled. No patients with mesothelioma or other mesothelin-producing cancers were included. Mesothelin was measured in matched blood and urine samples. The researchers also measured urinary albumin, a marker of leakage through the kidney's filters, and alpha 1-microglobulin, a marker of reduced reabsorption by the kidney tubules. Median mesothelin was 0.58 nmol/L in urine and 1.74 nmol/L in serum, a statistically significant difference. With all three urinary measurements divided by urinary creatinine, urinary mesothelin rose with albumin (r = 0.51) and with alpha 1-microglobulin (r = 0.71). It was not associated with age or with estimated kidney filtration rate. In a combined analysis, only albumin and alpha 1-microglobulin were independently associated with it. The authors concluded that damage to kidney filtering and reabsorption affects urinary mesothelin and might cause false-positive results. They said the findings need confirming in patients with mesothelioma and ovarian cancer.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: prospective study of consecutively enrolled patients, with mesothelin and kidney-function markers measured in matched serum and urine samples
• Who was studied: 75 white patients (47 men, 28 women) with benign kidney disease, enrolled at the Department of Nephrology, Ghent University Hospital, Belgium, between November and December 2010
• Exposure: No asbestos exposure was studied. The study examined how kidney function (estimated GFR, urinary albumin and urinary alpha 1-microglobulin) related to mesothelin levels, measured in serum and urine with the Mesomark ELISA. The authors describe mesothelin as a soluble biomarker of malignant mesothelioma.
• Main results:
  • In the 75 patients, absolute urinary mesothelin levels (median 0.58 nmol/L, IQR 0.25-1.03) were significantly lower than serum levels (median 1.74 nmol/L, IQR 1.35-2.43), P less than .001
  • Nine (12%) of the 75 participants had urinary mesothelin below the detection limit. The other 66 patients had detectable urinary levels, and all participants had detectable serum levels.
  • Absolute urinary and serum mesothelin levels were not correlated. Creatinine-standardized urinary mesothelin did correlate with serum mesothelin (r = 0.35, P less than .01).
  • Creatinine-standardized urinary mesothelin correlated with creatinine-standardized urinary albumin (r = 0.51) and creatinine-standardized alpha 1-microglobulin (r = 0.71), both P less than .001
  • Neither age nor estimated GFR was associated with standardized urinary mesothelin, and levels did not differ across chronic kidney disease stages
  • In multiple linear regression in all 75 patients, only standardized albumin and alpha 1-microglobulin were independently associated with standardized urinary mesothelin (adjusted R2 0.49). The result was the same in the 66 patients with detectable levels (adjusted R2 0.47).
  • The 25 patients with the lowest standardized albumin or alpha 1-microglobulin levels had significantly lower standardized urinary mesothelin than the 25 patients with the highest levels (P less than .0001)
  • Serum mesothelin was not associated with standardized albumin or alpha 1-microglobulin. The authors did not show these data.
• The authors' conclusion: The authors concluded that urinary mesothelin levels are affected by increased glomerular leakage and impaired tubular reabsorption. They said this can influence how measurements are interpreted, for example by causing false-positive results. They said these effects need to be accounted for in further validation studies and in any clinical use.
• Limitations the authors state:
  • The study did not include patients with a mesothelin-expressing cancer, so the findings need to be confirmed in patients with mesothelioma and ovarian cancer
  • Mesothelin levels in urine are low, and lower concentrations are subject to higher ELISA variability
  • Other factors that might affect urinary mesothelin remain to be identified

Topics

Medical terms in this study, explained in our Lexicon: Mesothelin, Biomarker, Mesothelioma, EGFR.

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