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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2010  |  Volume : 21  |  Issue : 1  |  Page : 50-53
Measurement of tumor markers in chronic hemodialysis patients


1 Dialysis Unit, General Hospital of Korinthos, Korinthos, Greece
2 Urology Department, University of Crete, Iraklio, Greece

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Date of Web Publication8-Jan-2010
 

   Abstract 

Tumor markers are widely used for screening certain tumors, however, their use in chronic hemodialysis (HD) patients in hemodialysis has been a controversial issue. To determine the reliability of the tumor markers, CA 15-3, CA 19-9, CA 125, Alpha-Fetoprotein and Carcinoem­bryonic antigen (CEA), in chronic HD patients, and the impact of active hepatitis C on the variation of tumor markers values, we studied 30 patients (16 men and 14 women) aged from 40 to 78 years old (mean age: 54 ± 5 years), on intermittent hemodialysis (with a mean duration of 10.5 years), and clinically free from neoplastic disease. The control group included 30 healthy volunteers. All subjects were of Greek origin and residents of the Korinthos region. The tumor markers were measured once in the control group and before and afterwards the hemodialysis, in the study group. Alpha fetopro­tein was within normal limits in all the study patients, CA 125 was slightly increased in one (3.3%) patient, CA 15-3 levels were twice normal in 4 (13%) patients, CA 19-9 levels were twice normal in 5 (16%) patients, and CEA levels were twice normal in 4(13%) patients. More than half (7/13) of anti HCV positive and all Australian antigen positive patients had abnormal serum levels of CA 15­3 and CA 125 after hemodialysis treatment. We conclude that measurement of some tumor markers such as alfa-fetoprotein may be beneficial in HD patients. However, the elevated levels of other markers including CA 15-3 and CA 125 are not specific for neoplasms and related to active hepatitis C.

How to cite this article:
Tzitzikos G, Saridi M, Filippopoulou T, Makri A, Goulioti A, Stavropoulos T, Stamatiou K. Measurement of tumor markers in chronic hemodialysis patients. Saudi J Kidney Dis Transpl 2010;21:50-3

How to cite this URL:
Tzitzikos G, Saridi M, Filippopoulou T, Makri A, Goulioti A, Stavropoulos T, Stamatiou K. Measurement of tumor markers in chronic hemodialysis patients. Saudi J Kidney Dis Transpl [serial online] 2010 [cited 2020 Jan 28];21:50-3. Available from: http://www.sjkdt.org/text.asp?2010/21/1/50/58709

   Introduction Top


Neoplastic cells secrete proteins that can mark their activities. The first tumor marker was dis­covered in 1847; however, now more than 100 different tumor markers are available at the dis­posal of oncologists. Tumor markers can be use­ful to exclude active malignant disease in the candidates for transplantation and hemodialysis (HD) patients, who are at increased risk of deve­loping malignancy [1] . Since renal or hepatic fai­lure sustains the T1/2 of tumor markers kine­tics, the use of the tumor markers in HD patients has been a controversial issue. [2],[3]

The aim of our study is to measure the most common tumor markers, CA 15-3, CA 19-9, CA 125, alpha-fetoprotein and carcinoembryonic an­tigen (CEA), in HD patients and evaluate whether they can be used to screen for neoplasms. In addi­tion, we assessed the impact of antigen (CEA), in HD patients and evaluate whether they can be used to screen for neoplasms. In addition, we assessed the impact of active hepatitis C on the variation of tumor markers levels.


   Material and Methods Top


Patients and controls

We studied chronic HD patients treated at our dialysis unit between November 2006 and No­vember 2007. We excluded patients with a prior history of cancer in any organ as well as pa­tients suspicious of having malignant disease at the enrolment. The control group included 30 healthy volunteers meeting the same exclusion criteria. All subjects were of Greek origin and residents of the Korinthos region. Participants were enrolled if they had CA 15-3, CA 19-9, CA 125, Alpha-Fetoprotein and CEA values within normal ranges at time of enrolment. Informed consents were obtained from all pa­tients. The study was approved by the local ethic committee and performed in accordance with the International Conference on Harmoni­sation Guideline for Good Clinical Practice (1996), which represents the international ethi­cal and scientific quality standard for designing, conducting, recording, and reporting trials that involve participation of human subjects.

Blood collection and measures

One blood sample was collected from each control subject. In contrast, two blood samples were collected from each patient in the study group; both were obtained immediately before and after HD sessions. The blood samples were allowed to clot in the room temperature for 20 minutes and then centrifuged at 2000 g for 15 minutes. The serum was then immediately fro­zen and stored at -20°C. Serum CA 15-3, CA 19-9, CA 125, alpha-Fetoprotein, and CEA le­vels were measured with the Electro ChemiL uminescence (ELC) method on the commer­cially available ELECSYS 2010 analyzer from Roche.

We also tested the blood samples of the study patients for the presence of hepatitis C infection by measuring both the anti-HCV antibodies and the viral load by PCR-RNA.


   Statistical Analysis Top


Data were entered into an electronic database for statistical analysis purpose. Statistical signi­ficance was measured using the SPSS statistical program. The associations among variables were assessed by Student's t-test. The significance was set at P <0.05.


   Results Top


The study group consisted of 30 (16 men and 14 women) aged from 40 to 78 years old (mean 54.5 years old) on treatment for at least two years with cellulosic or semi-synthetic mem­branes. Causes of ESRD included glomerulo­nephritis in 12 (40%) patients, polycystic kidney disease in 9 (30%) patients, and diabetes in 9 (30%) patients. Dialysis was performed as stan­dard 4 hours sessions three times a week.

CEA serum levels were found twice normal in one (3.3%) patient, CA 15-3 serum levels twice normal in four (13%) (P= 0.039), and CA 19-9 twice normal in 5 (16%) (P= 0.019). A slight increase of CA 125 serum levels above normal ranges were found in 6 patients. In contrast, va­lues of serum alpha fetoprotein were found within normal ranges in all the study patients. Due to the relatively small sample, none of the above tumor markers variations was significant in the statistical analyses.

Thirteen out of the 30 (39.70%) patients were found anti HCV positive, and one (3.3%) was Australian antigen positive. Six out of the 13 (40.6%) anti-HCV positive patients had a nega­tive PCR-RNA test. Remarkably, more than 50% (7/13) of the anti-HCV positive patients revealed abnormal serum levels of CA 125 and CA 15-3.


   Discussion Top


During the past decades, several in vitro and in vivo reports have questioned the reliability of the measurement of tumor markers in HD pa­tients by demonstrating significant variances in the concentration of some tumor markers after HD sessions. However, in our study, serum alfa­fetoprotein concentrations remained unaltered after the HD session, a finding which is com­parable with other studies. [4],[5],[6],[7],[8] In contrast, serum CA 15-3 tends to reach serum levels twice nor­mal after HD in 13% of our patients, a finding which is also in accordance with studies else-where [9],[10],[11] . CA 15-3 levels are most useful in fol­lowing the course of treatment in women diag­nosed with early and advanced breast cancer. Cancers of ovary, lung, and prostate may also raise CA 15-3 levels. Elevated levels of CA 15­3 may be associated with noncancerous condi­tions, such as benign breast or ovarian disease, endometriosis, pelvic inflammatory disease, and hepatitis. In our study, the increased serum le­vels of CA15-3 were probably due to the con­comitant hepatitis C infection.

Previous studies demonstrated similar results to our study regarding the increase of CA 19-9 serum levels after HD treatment; [5],[7],[8],[9],[12] however, not confirmed by statistical analysis. Further­more, serum CEA concentrations strongly tend to duplicate after HD treatment. [2],[8],[9],[12],[13],[14] In only two studies differences in serum CEA levels prior to and after HD treatment were not of statistical significance. [15],[16] However, no cross­ correlation has been found between serum CEA variations and total durations of the HD, types of dialyzer membranes, specific kidney diseases, and patients' ages. [8],[12] Interestingly, Polenakovic et al suggested that the mean increase of CEA values after HD treatment did not exceed the upper limit of the normal values. [8]

Although Camci et al proposed that patients on dialysis had significantly elevated serum CA125 levels, [17] reported variations of serum CA125 levels in HD patients are large, ranging from 1 to 18%. [2],[9],[8],[16] Furthermore, it appears that the increase in serum levels of CA125 is gender specific. Similar to our findings, Xiao-fang et al found that serum levels of CA125 increase after HD treatment only in male patients. [18] To our knowledge, increased serum levels of CA125 in women are strongly correlated with ovarian car­cinoma. In fact, they are present on more than 80% of nonmucinous ovarian carcinomas. Des­pite its high sensitivity, CA 125 is not specific for ovarian cancer but rather indicates activa­tion of mesothelial cells in response to various stimuli. In our study, the increased serum levels of CA125 were probably due to concomitant hepatitis C infection.

We conclude that measurement of some tumor markers such as alfa-fetoprotein may be bene­ficial in HD patients. However, the elevated le­vels of other markers including CA 15-3 and CA 125 are not specific for neoplasms and related to active hepatitis C.[Figure 1]

 
   References Top

1.Lye WC, Tambyah P, Leong SO, Lee EJ. Serum tumor markers in patients on dialysis and kidney transplantation. Adv Perit Dial 1994;10: 109-11.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]  
2.Pecchio F, Rapellino M, Ruffini E, Cavallo A. Half-life of CEA after curative resection of adenocarcinima of the lung. Int J Biol Markers 1992;7:119-20.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]  
3.Rapellino M, Piantino P, Pecchio F, et al. Dis­appearance curves of tumor markers after radi­cal surgery. Int J Biol Markers 1994;9:33-7.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]  
4.Bertolini L, Meschi M, Detrenis S, Maggiore U, Savazzi G. Serum concentration of some tumor markers in renal failure. Recenti Prog Med 2005;96(5):221-5.  Back to cited text no. 4      
5.Arik N, Adam B, Akpolat T, Hasil K, Tabak S. Serum tumour markers in renal failure. Int Urol Nephrol 1996;28(4):601-4.  Back to cited text no. 5      
6.Odagiri E, Jibiki K, Takeda M, et al. Effect of hemodialysis on the concentration of the seven tumor markers carcinoembryonic antigen, alpha­fetoprotein, squamous cell carcinoma-related antigen, neuron-specific enolase, CA 125, CA 19-9 and CA 15-3 in uremic patients. Am J Nephrol 1991;11(5):363-8.  Back to cited text no. 6      
7.Filella X, Cases A, Molina R, et al. Tumor markers in patients with chronic renal failure. Int J Biol Markers 1990;5(2):85-8.  Back to cited text no. 7      
8.Polenakovic M, Sikole A, Dzikova S, Polena­kovic B, Gelev S. Acquired renal cystic disease and tumor markers in chronic hemodialysis patients. Int J Artif Organs 1997;20(2):96-100.  Back to cited text no. 8      
9.Zeferos N, Digenis GE, Christophoraki M, et al. Tumor markers in patients undergoing hemo­dialysis or kidney transplantation. Nephron 1991; 59(4):618-20.  Back to cited text no. 9      
10.Odagiri E, Jibiki K, Takeda M, et al. Effect of hemodialysis on the concentration of the seven tumor markers carcinoembryonic antigen, alpha­fetoprotein, squamous cell carcinoma-related an­tigen, neuron-specific enolase, CA 125, CA 19­9 and CA 15-3 in uremic patients, Am J Nephrol 1991;11(5):363-8.  Back to cited text no. 10      
11.Okada T, Nakao T, Matsumoto H. Dialysate CA 125 levels in stable peritoneal dialysis patients. Clin Nephrol. 1999;51(1):65-6.  Back to cited text no. 11      
12.Kashiwabara K, Nakamura H, Yagyu H, Kishi K, Matsuoka T, Esaki T. Changes in squamous cell carcinoma-related antigen levels before and after hemodialysis in relation to the model of dialyzer employed. Intern Med 2000;39(4):291­-5.  Back to cited text no. 12      
13.Walz G, Kunzendorf U, Keller F, Fitzner R, Offermann G. Elevated tumor markers in hemo­dialysis patients. Am J Nephrol 1988;8(3):187­-9.  Back to cited text no. 13      
14.Bastani B, Chu N. Serum CA-125 level in end­stage renal disease patients maintained on chro­nic peritoneal dialysis or hemodialysis: the effect of continuous presence of peritoneal fluid, peritonitis, and peritoneal catheter implantation. Am J Nephrol 1995;15(6):468-72.  Back to cited text no. 14      
15.Gonzalez Vitores AM, Encabo Duro G, Bermejo Fraile B, Olmos Miro A, Armengol Carrasco M. Utility of tumor marker CA 72.4 in patients with chronic renal failure. Int J Biol Markers 1999;14(2):118-21.  Back to cited text no. 15      
16.Menzin AW, Kobrin S, Pollak E, Goodman DB, Rubin SC. The effect of renal function on serum levels of CA 125 Gynecol Oncol 1995;58(3): 375-7.  Back to cited text no. 16      
17.Camci C, Boyokberber S, Tarakrlioglu M, et al. The effect of continuous ambulatory peritoneal dialysis on serum CA-125 levels. Eur J Gynaecol Oncol 2002;23(5):472-4.  Back to cited text no. 17      
18.Xiaofang Y, Yue Z, Xialian X, Zhibin Y. Serum tumor markers in patients with chronic kidney disease. Scand J Clin Lab Invest 2007;67(6): 661-7.  Back to cited text no. 18      

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Correspondence Address:
K Stamatiou
University of Crete, Urology Department, Salepoula 2 Piraeus
Greece
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PMID: 20061692

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    Abstract
    Introduction
    Material and Methods
    Statistical Analysis
    Results
    Discussion
    References
    Article Figures
 

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