Mesothelin and kidney function--analysis of relationship and implications for mesothelioma screening

Our plain-English summary of Mesothelin and kidney function--analysis of relationship and implications for mesothelioma screening, by N. Boudville, R. Paul, B.W. Robinson, et al (Lung Cancer, 2011).

The study

• Authors: N. Boudville, R. Paul, B.W. Robinson, J. Creaney
• Journal: Lung Cancer
• Published: 2011;73(3):320-4
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose: Malignant mesothelioma (MM) carries a poor prognosis and remains a major public health issue in many countries. Outcomes may be improved with earlier detection and this justifies screening the at-risk asbestos-exposed population. Soluble mesothelin is a potential biomarker for MM, but it has been observed to be elevated in patients with reduced kidney function. Defining the relationship between mesothelin concentrations and kidney function will allow more accurate interpretation of this assay.

Materials And Methods: A cross-sectional study consisting of 144 patients with chronic kidney disease (CKD) was conducted at Sir Charles Gairdner Hospital and Royal Perth Hospital in Western Australia. Only patients with CKD stages II-V were recruited while those with a history of renal transplant, dialysis, or malignancy were excluded. Serum and urine mesothelin and creatinine concentrations were determined.

Results: There were 33, 49, 31 and 31 patients in CKD stages II, III, IV and V, respectively recruited. Serum mesothelin increased significantly with increasing serum creatinine (p<0.0001), and worsening stage of CKD (p<0.0001). A significant correlation between urine mesothelin to creatinine ratio and serum mesothelin concentration was detected (p=0.002). No significant difference was found in urine mesothelin to creatinine ratios across the four CKD stage groups.

Conclusion: Serum mesothelin concentration is elevated in individuals with renal impairment. Renal function should therefore be taken into account during interpretation of this assay.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

In plain English

This cross-sectional study at two Western Australian hospitals examined whether kidney function affects soluble mesothelin, a blood marker studied for detecting malignant mesothelioma. It included 144 adults with chronic kidney disease stages II to V. People on dialysis, with a kidney transplant, or with a past cancer were excluded. Serum mesothelin rose as kidney function worsened. Median levels were 1.0 nM in stage II, 1.6 in stage III, 2.45 in stage IV and 2.6 in stage V. In all, 41 of 144 patients (28%) had serum mesothelin of 2.5 nM or greater. Age, sex, smoking, self-reported asbestos exposure and diabetes were not significantly associated with serum mesothelin. Urine mesothelin was below the detection limit in 58 of 124 patients and showed no correlation with kidney function measures. The authors concluded that reduced kidney function is likely to produce a false positive mesothelin measurement. They noted that this assumed none of their patients had undetected mesothelioma or other cancer, which they called a weakness of the study.

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: cross-sectional study
• Who was studied: 144 adults (82 males, 62 females) with chronic kidney disease (CKD) stages II to V at Sir Charles Gairdner Hospital and Royal Perth Hospital, Western Australia: 33, 49, 31 and 31 patients in stages II, III, IV and V respectively. They were recruited from nephrology outpatient clinics and from inpatients admitted for non-renal conditions. People under 18, on peritoneal dialysis or haemodialysis, with a previous kidney transplant, or with a history of malignancy were excluded. Study dates are not given.
• Exposure: The main factor studied was kidney function: CKD stage, serum creatinine and estimated glomerular filtration rate (eGFR). It was related to soluble mesothelin in serum and urine, measured with the Mesomark ELISA kit. Asbestos exposure was self-reported by questionnaire; Table 1 lists 37 (25.7%) patients as exposed. No fiber types or jobs are described.
• Main results:
  • Median (range) serum mesothelin by CKD stage: stage II 1.0 (0.3 to 3.1) nM, stage III 1.6 (0.3 to 4.8) nM, stage IV 2.45 (1.1 to 4.5) nM, stage V 2.6 (0.8 to 6.7) nM.
  • Serum mesothelin in the stage II group was significantly different from that in the stage III to V groups (p less than 0.005).
  • Serum mesothelin correlated with serum creatinine (r-squared 0.28, p less than 0.0001).
  • Serum mesothelin was associated with eGFR (Spearman r = -0.57, p less than 0.0001): higher mesothelin went with lower kidney function.
  • 41 of 144 participants (28%) had serum mesothelin of 2.5 nM or greater, including about 50% of those with stage IV and V CKD.
  • Age, sex, smoking, asbestos exposure and diabetes were not significantly associated with serum mesothelin.
  • Urine mesothelin was below the assay's detection limit in 58 of 124 (47%) patients who gave urine samples.
  • Urine mesothelin did not correlate with serum creatinine or eGFR.
  • Urine mesothelin corrected for urine creatinine did not differ significantly across the four CKD stages.
  • Among patients with measurable urine mesothelin, the urine mesothelin to creatinine ratio correlated with serum mesothelin (Spearman r = 0.33; p = 0.007).
• The authors' conclusion: The authors concluded from their observations that reduced kidney function is likely to produce a false positive mesothelin measurement. Earlier in the discussion they wrote that the close relationship between kidney failure and serum mesothelin suggests chronic kidney disease will give false positive results.
• Limitations the authors state:
  • The interpretation of high mesothelin as false positives assumes that none of the recruited patients had mesothelioma or another undetected cancer. The authors called this a weakness of the study.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

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

Related studies

• Serum soluble mesothelin concentrations in malignant pleural mesothelioma: relationship to tumor volume, clinical stage and changes in tumor burden — J. Creaney, R.J. Francis, et al. (2011)
• Comparison of the diagnostic accuracy of the MSLN gene products, mesothelin and megakaryocyte potentiating factor, as biomarkers for mesothelioma in pleural effusions and serum — J. Creaney, S. Sneddon, et al. (2013)
• The relationship between tumor MSLN methylation and serum mesothelin (SMRP) in mesothelioma — H.H. Nelson, L.M. Almquist, et al. (2011)
• Plasma versus serum levels of osteopontin and mesothelin in patients with malignant mesothelioma--which is best? — J. Creaney, D. Yeoman, et al. (2011)
• Pleural fluid mesothelin as an adjunct to the diagnosis of pleural malignant mesothelioma — J. Creaney, A. Segal, et al. (2014)
• Does CA125 binding to mesothelin impact the detection of malignant mesothelioma? — J. Creaney, I.M. Dick, et al. (2013)

Browse more research in Lung Cancer, or return to medical research.