Original Paper Urol Int 1992;48:181-183
Department of Urology, Yamagata University, School of Medicine, Yamagata, Japan
Key Words Prostatic acid phosphatase y-Seminoprotein Prostatic specific antigen Hemodialysis
Serum Prostatic Acid Phosphatase, GammaSeminoprotein and Prostatic Specific Antigen in Hemodialysis Patients
Abstract Serum concentrations of prostatic acid phosphatase (PAP), y-seminoprotein (y-Sm) and prostatic specific antigen (PSA) were measured in 31 hemodialysis patients without clinical signs of malignant disease. PAP, y-Sm and PSA levels in serum were not significantly different between control and hemodialysis groups. A significant reduction in these tumor markers was not found after dialysis treatment. This indicates that the measurement of PAP, y-Sm and PSA in serum is useful for the detection of prostatic cancer in patients undergoing hemodialysis.
introduction
Materials and Methods
Prostatic acid phosphatase (PAP), y-seminoprotein (y-Sm) and prostatic specific antigen (PSA) have been widely used as tumor markers for the detection of patients with prostatic cancer [1 ]. In patients with metastatic dis ease, these tumor markers have reflected the degree of dis ease progression or response to treatment [2], However, literature dealing with serum levels of PAP, y-Sm and PSA in patients with end-stage renal disease on mainte nance hemodialysis is very limited [3, 4], In this study, we examined serum concentrations of PAP, y-Sm and PSA from patients undergoing hemodial ysis, and discuss the influence of renal failure on these tumor markers.
Received: July 8. 1991 Accepted: August 19, 1991
Thirty-one male patients with end-stage renal disease, aged 2976 years (median 52 years), were included in this study. All patients had been managed by hemodialysis for 4-215 months (median 73 months). There was no clinical evidence of malignancies in the patients under investigation. They were dialyzed 10-12 h per square meter per week in two or three sessions. A capillary flow dialyzer with cuprophane membrane (BK-1.6U, Toray, Tokyo, Japan) was used. The rate of blood flow was about 150 ml/min, and the rate of water flow was approximetaly 500 ml/min. Blood samples were obtained from the arteriovenous fistula immediately before and after the first weekly hemodialysis session. Serum samples were stored at -8 0 °C until measurement. Serum PAP was determined with a commercially available radioimmunoas say kit (Eiken Chemical, Tokyo, Japan). Enzyme immunoassay kits (Chugai Pharmaceutical, Tokyo, Japan) were used for the determina tion of y-Sm. Serum PSA was measured with a radioimmunoassay
Isoji Sasagawa. MD Department of Urology Yamagata University School of Medicine 2-2-2 lidanishi, Yamagata-shi, Yamagata 990-23 (Japan)
© 1992 S. Kargcr AG. Basel 0042-1138/92/0482-0181 $2.75/0
Downloaded by: University of Connecticut 132.174.250.220 - 1/6/2020 12:40:06 PM
Isoji Sasagawa Teruhiro Nakada Tohru Hashimoto Manabu Ishigooka Yoko Kubota Kazuhiko Hirano Junji Hirano Yukihiro Suzuki
10-
5-
o> 0.05. Fig. 3. Correlation between serum PSA and creatinine levels in patients receiving hemodialysis before each trial (n = 31). y = 0.18 + 0. lOx, r = 0.21, p > 0.05.
kit (CIS Bio International. Paris. France). Creatinine level in serum was measured by Jaffe’s method. As a control group, serum levels of PAP, y-Sm, PSA and creati nine were also examined in 16 men (aged 44-65 years, median 60 years) without clinical evidence of neoplasia or other benign condi tions that could affect the results.
Results Serum creatinine level of hemodialysis patients was abnormally higher than that of controls (p < 0.001). In patients receiving hemodialysis, serum level of creatinine significantly decreased after hemodialysis treatment (p < 0.001; table 1). As shown in table 2, serum levels of PAP, y-Sm and PSA were not significantly different between control and hemodialysis patients. A significant reduction in these tumor markers was not observed after dialysis therapy. A correlation between serum creatinine and PAP lev els was seen in patients undergoing hemodialysis (r = 0.71, p < 0.001; fig. 1). No correlation was found between serum creatinine and the other tumor markers (fig. 2,3).
Sasagawa/Nakada/Hashimoto/Ishigooka/ Kubota/Hirano/Hirano/Suzuki
Tumor Markers in Hemodialysis Patients
Downloaded by: University of Connecticut 132.174.250.220 - 1/6/2020 12:40:06 PM
B
GO
Discussion Matas et al. [5] first described an increased incidence of malignancies in chronic renal failure. This rate was seven times the expected yearly incidence in the agematched general population. Also, a sixfold increase in prostatic cancer was observed among hemodialysis pa tients [6]. Several factors concerning the occurrence of cancer in uremia have been proposed: acquired renal cys tic disease [7], T-lymphocyte dysfunction [8], the extra corporeal elements used in hemodialysis and increased concentrations of nitrosamines in natural water [9], among others. However, clear demonstration for these factors is still lacking. Tumor markers are biological substances that are pro duced by cancer cells. However, small amounts of such substances are found in normal tissues, with the existence of certain circulating amounts of these markers being physiological. Some tumor markers are influenced by
hepatobiliary disease [10] and renal disease [11, 12], In patients undergoing hemodialysis, the suppression of the renal function is substituted by a dialysis membrane which allows the filtering of molecules and small molecu lar weights [ 13]. Usually, tumor markers with high molec ular weights cannot be removed by hemodialysis. The molecular weights of PAP, y-Sm and PSA are 100,000, 23,000 and 34,000, respectively [14-16], Therefore, se rum levels of these tumor markers did not significantly decrease after dialysis treatment in patients receiving hemodialysis. However, these tumor markers in serum were not significantly different between control and he modialysis groups. This means that the removal of these tumors markers is not affected by glomerular filtration, but other systems may be involved. Based on these results, we consider that the measurement of PAP. y-Sm and PSA in serum is valuable for the detection of prostatic cancer even in patients with end-stage renal disease on maintenance hemodialysis.
References 7 Dunnill MS. Millard PR. Oliver D: Acquired cystic disease of the kidneys. A hazard of long term intermittent maintenance hemodialysis. J Clin Pathol 1977;30:868-877. 8 Goldblum SE. Reed WP: Host defenses and immunologic alterations associated with chronic hemodialysis. Ann Intern Med 1980: 93:597-613. 9 Curtis JR: Cancer and patients with end-stage renal failure. Br Med J 1982:284:69-70. 10 Lurie BB. Locwcnstein MS, Zamcheck N: Ele vated circulating CEA levels in benign extrahepatic biliary tract obstruction and inflamma tion. JAMA 1975:233:326-330. 11 DeSanto NG. Veneroso S. Capodicasa G. et al: Tumor markers in uremia. Carcinoembryonic antigen, neuron-specific enolase. carbohydrate antigen CA-50 and a-fetroprotein. Am J Ne phrol 1986;6:458-463.
12 Docc: D. Pistocchi E, Turci F. et al: Scrum CA 19-9 and CA 50 antigens in hemodialysis patients. Clin Nephrol 1987:27:179-181. 13 Brenner BM. Hostetter TH. Humes HD: Mo lecular basis of proteinuria of glomerular ori gin. N Engl J Med 1978:298:826-833. 14 King EJ. Jegatheesan KA: A method for the determination of tartrate labile, prostatic acid phosphatase in serum. J Clin Pathol 1959:12: 85. 15 HaraS. InoueT. Koyanagi Y. et al: Preparation and immunoelectrophoretic assessment of an tisera to human seminal plasma. Jpn J Leg Med 1966:20:356. 16 Wang MC. Valenzuela LA. Murphy GP. et al: Purification of a human prostate specific anti gen. Invest Urol 1979:17:159-163.
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1 Arai Y. Yoshiki T, Okada T, et al: Multiple marker evaluation in prostatic cancer using prostatic specific antigen, gamma-seminoprotein and prostatic acid phosphatases. Urol Int 1989:44:135-140. 2 Kaplan J. Prestidge BR, Cox RS. et al: Prostatic specific antigen after irradiation for proslatic carcinoma. J Urol 1990:144:1172-1176. 3 Filella X, Cases A. Moline R. et al: Tumor markers in patients with chronic renal failure. Int J Biol Markers 1990:5:85-88. 4 Kabalin JN. Ilornberger JC: Prostatic specific antigen is not excreted by human kidney or eliminated by routine hemodialysis. Urology 1991:37:3082310. 5 Matas AJ. Simmonds RI.. Kjellstrand CM, et al: Increased incidence of malignancy during chronic renal failure. Lancet 1975:i:883—885. 6 Sasagawa 1. Suzuki K. Ishizaki M. et al: Pros tatic cancer in a patient on long-term hemodi alysis. Nephron 1991:59:506-507.
Department of Urology, Yamagata University, School of Medicine, Yamagata, Japan
Key Words Prostatic acid phosphatase y-Seminoprotein Prostatic specific antigen Hemodialysis
Serum Prostatic Acid Phosphatase, GammaSeminoprotein and Prostatic Specific Antigen in Hemodialysis Patients
Abstract Serum concentrations of prostatic acid phosphatase (PAP), y-seminoprotein (y-Sm) and prostatic specific antigen (PSA) were measured in 31 hemodialysis patients without clinical signs of malignant disease. PAP, y-Sm and PSA levels in serum were not significantly different between control and hemodialysis groups. A significant reduction in these tumor markers was not found after dialysis treatment. This indicates that the measurement of PAP, y-Sm and PSA in serum is useful for the detection of prostatic cancer in patients undergoing hemodialysis.
introduction
Materials and Methods
Prostatic acid phosphatase (PAP), y-seminoprotein (y-Sm) and prostatic specific antigen (PSA) have been widely used as tumor markers for the detection of patients with prostatic cancer [1 ]. In patients with metastatic dis ease, these tumor markers have reflected the degree of dis ease progression or response to treatment [2], However, literature dealing with serum levels of PAP, y-Sm and PSA in patients with end-stage renal disease on mainte nance hemodialysis is very limited [3, 4], In this study, we examined serum concentrations of PAP, y-Sm and PSA from patients undergoing hemodial ysis, and discuss the influence of renal failure on these tumor markers.
Received: July 8. 1991 Accepted: August 19, 1991
Thirty-one male patients with end-stage renal disease, aged 2976 years (median 52 years), were included in this study. All patients had been managed by hemodialysis for 4-215 months (median 73 months). There was no clinical evidence of malignancies in the patients under investigation. They were dialyzed 10-12 h per square meter per week in two or three sessions. A capillary flow dialyzer with cuprophane membrane (BK-1.6U, Toray, Tokyo, Japan) was used. The rate of blood flow was about 150 ml/min, and the rate of water flow was approximetaly 500 ml/min. Blood samples were obtained from the arteriovenous fistula immediately before and after the first weekly hemodialysis session. Serum samples were stored at -8 0 °C until measurement. Serum PAP was determined with a commercially available radioimmunoas say kit (Eiken Chemical, Tokyo, Japan). Enzyme immunoassay kits (Chugai Pharmaceutical, Tokyo, Japan) were used for the determina tion of y-Sm. Serum PSA was measured with a radioimmunoassay
Isoji Sasagawa. MD Department of Urology Yamagata University School of Medicine 2-2-2 lidanishi, Yamagata-shi, Yamagata 990-23 (Japan)
© 1992 S. Kargcr AG. Basel 0042-1138/92/0482-0181 $2.75/0
Downloaded by: University of Connecticut 132.174.250.220 - 1/6/2020 12:40:06 PM
Isoji Sasagawa Teruhiro Nakada Tohru Hashimoto Manabu Ishigooka Yoko Kubota Kazuhiko Hirano Junji Hirano Yukihiro Suzuki
10-
5-
o> 0.05. Fig. 3. Correlation between serum PSA and creatinine levels in patients receiving hemodialysis before each trial (n = 31). y = 0.18 + 0. lOx, r = 0.21, p > 0.05.
kit (CIS Bio International. Paris. France). Creatinine level in serum was measured by Jaffe’s method. As a control group, serum levels of PAP, y-Sm, PSA and creati nine were also examined in 16 men (aged 44-65 years, median 60 years) without clinical evidence of neoplasia or other benign condi tions that could affect the results.
Results Serum creatinine level of hemodialysis patients was abnormally higher than that of controls (p < 0.001). In patients receiving hemodialysis, serum level of creatinine significantly decreased after hemodialysis treatment (p < 0.001; table 1). As shown in table 2, serum levels of PAP, y-Sm and PSA were not significantly different between control and hemodialysis patients. A significant reduction in these tumor markers was not observed after dialysis therapy. A correlation between serum creatinine and PAP lev els was seen in patients undergoing hemodialysis (r = 0.71, p < 0.001; fig. 1). No correlation was found between serum creatinine and the other tumor markers (fig. 2,3).
Sasagawa/Nakada/Hashimoto/Ishigooka/ Kubota/Hirano/Hirano/Suzuki
Tumor Markers in Hemodialysis Patients
Downloaded by: University of Connecticut 132.174.250.220 - 1/6/2020 12:40:06 PM
B
GO
Discussion Matas et al. [5] first described an increased incidence of malignancies in chronic renal failure. This rate was seven times the expected yearly incidence in the agematched general population. Also, a sixfold increase in prostatic cancer was observed among hemodialysis pa tients [6]. Several factors concerning the occurrence of cancer in uremia have been proposed: acquired renal cys tic disease [7], T-lymphocyte dysfunction [8], the extra corporeal elements used in hemodialysis and increased concentrations of nitrosamines in natural water [9], among others. However, clear demonstration for these factors is still lacking. Tumor markers are biological substances that are pro duced by cancer cells. However, small amounts of such substances are found in normal tissues, with the existence of certain circulating amounts of these markers being physiological. Some tumor markers are influenced by
hepatobiliary disease [10] and renal disease [11, 12], In patients undergoing hemodialysis, the suppression of the renal function is substituted by a dialysis membrane which allows the filtering of molecules and small molecu lar weights [ 13]. Usually, tumor markers with high molec ular weights cannot be removed by hemodialysis. The molecular weights of PAP, y-Sm and PSA are 100,000, 23,000 and 34,000, respectively [14-16], Therefore, se rum levels of these tumor markers did not significantly decrease after dialysis treatment in patients receiving hemodialysis. However, these tumor markers in serum were not significantly different between control and he modialysis groups. This means that the removal of these tumors markers is not affected by glomerular filtration, but other systems may be involved. Based on these results, we consider that the measurement of PAP. y-Sm and PSA in serum is valuable for the detection of prostatic cancer even in patients with end-stage renal disease on maintenance hemodialysis.
References 7 Dunnill MS. Millard PR. Oliver D: Acquired cystic disease of the kidneys. A hazard of long term intermittent maintenance hemodialysis. J Clin Pathol 1977;30:868-877. 8 Goldblum SE. Reed WP: Host defenses and immunologic alterations associated with chronic hemodialysis. Ann Intern Med 1980: 93:597-613. 9 Curtis JR: Cancer and patients with end-stage renal failure. Br Med J 1982:284:69-70. 10 Lurie BB. Locwcnstein MS, Zamcheck N: Ele vated circulating CEA levels in benign extrahepatic biliary tract obstruction and inflamma tion. JAMA 1975:233:326-330. 11 DeSanto NG. Veneroso S. Capodicasa G. et al: Tumor markers in uremia. Carcinoembryonic antigen, neuron-specific enolase. carbohydrate antigen CA-50 and a-fetroprotein. Am J Ne phrol 1986;6:458-463.
12 Docc: D. Pistocchi E, Turci F. et al: Scrum CA 19-9 and CA 50 antigens in hemodialysis patients. Clin Nephrol 1987:27:179-181. 13 Brenner BM. Hostetter TH. Humes HD: Mo lecular basis of proteinuria of glomerular ori gin. N Engl J Med 1978:298:826-833. 14 King EJ. Jegatheesan KA: A method for the determination of tartrate labile, prostatic acid phosphatase in serum. J Clin Pathol 1959:12: 85. 15 HaraS. InoueT. Koyanagi Y. et al: Preparation and immunoelectrophoretic assessment of an tisera to human seminal plasma. Jpn J Leg Med 1966:20:356. 16 Wang MC. Valenzuela LA. Murphy GP. et al: Purification of a human prostate specific anti gen. Invest Urol 1979:17:159-163.
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1 Arai Y. Yoshiki T, Okada T, et al: Multiple marker evaluation in prostatic cancer using prostatic specific antigen, gamma-seminoprotein and prostatic acid phosphatases. Urol Int 1989:44:135-140. 2 Kaplan J. Prestidge BR, Cox RS. et al: Prostatic specific antigen after irradiation for proslatic carcinoma. J Urol 1990:144:1172-1176. 3 Filella X, Cases A. Moline R. et al: Tumor markers in patients with chronic renal failure. Int J Biol Markers 1990:5:85-88. 4 Kabalin JN. Ilornberger JC: Prostatic specific antigen is not excreted by human kidney or eliminated by routine hemodialysis. Urology 1991:37:3082310. 5 Matas AJ. Simmonds RI.. Kjellstrand CM, et al: Increased incidence of malignancy during chronic renal failure. Lancet 1975:i:883—885. 6 Sasagawa 1. Suzuki K. Ishizaki M. et al: Pros tatic cancer in a patient on long-term hemodi alysis. Nephron 1991:59:506-507.
