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

Kevin Hollevoet UGent, MARIJN SPEECKAERT UGent, An-Sofie Decavele UGent, Raymond Vanholder UGent, Jan Van Meerbeeck UGent and Joris Delanghe UGent (2012) CLINICAL LUNG CANCER. 13(6). p.470-474
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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
Albumin, Alpha 1-microglobulin, Biomarker, Renal handling, Mesothelioma, MALIGNANT MESOTHELIOMA, FILTRATION-RATE, SERUM MESOTHELIN, OVARIAN-CANCER, DIFFERENTIATION, OSTEOPONTIN, SENSITIVITY, PROTEINS, MEGAKARYOCYTE POTENTIATING FACTOR, SOLUBLE MESOTHELIN, Urine
journal title
CLINICAL LUNG CANCER
Clin. Lung Cancer
volume
13
issue
6
pages
470 - 474
Web of Science type
Article
Web of Science id
000310411400010
JCR category
ONCOLOGY
JCR impact factor
2.038 (2012)
JCR rank
126/196 (2012)
JCR quartile
3 (2012)
ISSN
1525-7304
DOI
10.1016/j.cllc.2011.12.004
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
3029796
handle
http://hdl.handle.net/1854/LU-3029796
date created
2012-10-16 15:03:49
date last changed
2013-03-25 17:23:33
@article{3029796,
  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 {\textlangle} .001). Urinary mesothelin(std) levels positively correlated with serum mesothelin (r = 0.35, P {\textlangle} .01), albumin(std) (r = 0.51, P {\textlangle} .001), and A1M(std) levels (r = 0.71, P {\textlangle} .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.},
  author       = {Hollevoet, Kevin and SPEECKAERT, MARIJN and Decavele, An-Sofie and Vanholder, Raymond and Van Meerbeeck, Jan and Delanghe, Joris},
  issn         = {1525-7304},
  journal      = {CLINICAL LUNG CANCER},
  keyword      = {Albumin,Alpha 1-microglobulin,Biomarker,Renal handling,Mesothelioma,MALIGNANT MESOTHELIOMA,FILTRATION-RATE,SERUM MESOTHELIN,OVARIAN-CANCER,DIFFERENTIATION,OSTEOPONTIN,SENSITIVITY,PROTEINS,MEGAKARYOCYTE POTENTIATING FACTOR,SOLUBLE MESOTHELIN,Urine},
  language     = {eng},
  number       = {6},
  pages        = {470--474},
  title        = {Mesothelin levels in urine are affected by glomerular leakage and tubular reabsorption},
  url          = {http://dx.doi.org/10.1016/j.cllc.2011.12.004},
  volume       = {13},
  year         = {2012},
}

Chicago
Hollevoet, Kevin, MARIJN SPEECKAERT, An-Sofie Decavele, Raymond Vanholder, Jan Van Meerbeeck, and Joris Delanghe. 2012. “Mesothelin Levels in Urine Are Affected by Glomerular Leakage and Tubular Reabsorption.” Clinical Lung Cancer 13 (6): 470–474.
APA
Hollevoet, K., SPEECKAERT, M., Decavele, A.-S., Vanholder, R., Van Meerbeeck, J., & Delanghe, J. (2012). Mesothelin levels in urine are affected by glomerular leakage and tubular reabsorption. CLINICAL LUNG CANCER, 13(6), 470–474.
Vancouver
1.
Hollevoet K, SPEECKAERT M, Decavele A-S, Vanholder R, Van Meerbeeck J, Delanghe J. Mesothelin levels in urine are affected by glomerular leakage and tubular reabsorption. CLINICAL LUNG CANCER. 2012;13(6):470–4.
MLA
Hollevoet, Kevin, MARIJN SPEECKAERT, An-Sofie Decavele, et al. “Mesothelin Levels in Urine Are Affected by Glomerular Leakage and Tubular Reabsorption.” CLINICAL LUNG CANCER 13.6 (2012): 470–474. Print.