| 1. |
- Bruun, Laila, et al.
(författare)
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Assessment of intra-individual variation in prostate-specific antigen levels in a biennial randomized prostate cancer screening program in Sweden.
- 2005
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Ingår i: Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 65:3, s. 216-221
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Tidskriftsartikel (refereegranskat)abstract
- Abstract BACKGROUND The degree of variability in prostate-specific antigen (PSA) measurements is important for interpreting test results in screening programs, and particularly for interpreting the significance of changes between repeated tests. This study aimed to determine the long-term intra-individual variation for PSA in healthy men. METHODS A randomly selected cohort of men in a biennial prostate cancer screening program (ERSPC) conducted in Sweden from 1995-1996 to 2001-2002. We studied men who had total PSA (tPSA) levels < 2.0 ng/ml in 2001-2002. This included 791 men with tPSA 0.61 ng/ml (group A), 1,542 men with tPSA 0.99 ng/ml (group B), and 1,029 men with tPSA 1.00-1.99 ng/ml (group C). The intra-individual variability of free PSA (fPSA) and tPSA was assessed by calculating coefficients of variation (CV) for each individual's PSA measurements from the first and second round of screening (1995-1996 and 1997-1998). RESULTS Intra-individual CV (geometric means) for tPSA were 13.7%, 12.7%, and 11.5% in groups A, B, and C, respectively. Corresponding CVs for fPSA were significantly lower, ranging from 12.1% to 10.4%. The estimated biological variation of tPSA and fPSA in groups A to C were 12.5%, 11.4%, 10.0% and 9.7%, 7.8%, 7.5%, respectively. CONCLUSIONS In healthy men with PSA levels less than 2 ng/ml, the natural long-term variability for tPSA was less than 14%, and with 95% probability, a change in tPSA greater than 30% indicates a change beyond normal random variation. © 2005 Wiley-Liss, Inc.
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| 2. |
- Bruun, Laila
(författare)
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Impact of renal dysfunction on serum Prostate-Specific Antigen
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Measurement of prostate-specific antigen (PSA) in blood is an important tool in detection for prostate cancer. PSA occurs in several molecular forms in blood: mainly as a free form with a molecular mass of 28 kDa; and as PSA complexed to alpha-1-antichymotrypsin, complexed PSA, with a molecular mass of 90 kDa. Total PSA comprises the sum of free PSA and complexed PSA. The percentage of free-to-total PSA is frequently used due to its capacity to enhance the discrimination of prostate cancer from benign prostatic disorders. The assessed PSA concentration is, besides the production, also dependent on other factors such as the elimination and the intra-individual variability. Low-molecular-weight (LMW) proteins are extensively eliminated from plasma by glomerular filtration and as a consequence, plasma levels of these proteins are elevated in renal failure. The low molecular mass of free PSA, within the range of LMW proteins, and reported short half-life indicate elimination by glomerular filtration. The main interest in these studies was to describe the role of the kidneys in the elimination of free PSA, the effect of renal dysfunction on serum levels of PSA and percent free PSA, and to evaluate the intra-individual variation in PSA. We measured serum PSA in men with terminal renal failure on chronic dialysis treatment and demonstrated that patients on either hemodialysis or CAPD have increased percent free PSA but unaffected total PSA levels compared to controls. In men with terminal renal insufficiency, percent free PSA should be evaluated with caution in detection for prostate cancer as currently clinical cut-offs levels may not be applicable in uremic men. A high percent free PSA should not be considered as a sign of benign prostatic disorders in men with terminal renal failure. In order to study whether free PSA is eliminated by glomerular filtration, we investigated men undergoing renal transplantation. In this study we also included human kallikrein 2 (hK2), a new potential marker for prostate cancer. Plasma levels of free PSA and hK2 decreased rapidly after the transplantation, concluding that both proteins mainly are eliminated from the blood by glomerular filtration. We then evaluated whether moderate to severe renal dysfunction affects plasma levels of free PSA and percent free PSA. The studied men had a median glomerular filtration rate of 19.5 ml/min/1.73m2 (range; 8-54). We found significantly higher levels of free PSA and percent free PSA compared to controls. These findings show that renal function is an important factor to consider in the use of percent free PSA in detection of prostate cancer. The long-term intra-individual variation in PSA, over 2 years was evaluated in a cohort of men from the Göteborg screening study for prostate cancer. We included 2,571 men with total PSA less than 2 µg/l after 8 years of observation time. In seemingly healthy men, the long-term intra-individual variability in PSA was less than 14%, and with 95% probability, a change in total PSA greater than 30% indicates a change beyond normal variation.
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| 3. |
- Bruun, Laila, et al.
(författare)
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Increase in percent free prostate-specific antigen in men with chronic kidney disease.
- 2009
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Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 24:4, s. 1238-41
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prostate-specific antigen (PSA) occurs in different molecular forms in serum: free PSA (fPSA) and complexed PSA (cPSA), the sum of which corresponds to total PSA (tPSA). In addition to tPSA, percent fPSA is widely used in the detection of prostate cancer. Free PSA, approximately 28 kDa, is eliminated by glomerular filtration. Previous data showed that men with end-stage renal dysfunction requiring chronic dialysis have increased percent fPSA. In this study, we evaluated whether moderate-to-severe chronic renal dysfunction, but with no need for dialysis, also importantly affects percent fPSA. METHODS: The study group consisted of 101 men (median age 57 years, interquartile range 46-68) with chronic kidney disease and no diagnosis of prostate cancer. Their median glomerular filtration rate (GFR) was 23 mL/min/1.73 m(2) (interquartile range 16-33; range 8-83), determined by iohexol clearance. Controls included 5264 men (median age 57 years, interquartile range 54-62) attending a prostate cancer screening program with no diagnosis of prostate cancer during 8 years of follow-up. RESULTS: With adjustment for age, median fPSA levels and percent fPSA were significantly higher (P < 0.001) in patients with renal dysfunction, 0.45 microg/L and 47.2%, respectively, compared to controls, 0.29 microg/L and 29.9%, respectively. Regression analysis in the study group showed a significant association between GFR and percent fPSA (P = 0.036). CONCLUSIONS: The percent fPSA is importantly influenced by moderately impaired renal function in men with chronic kidney disease. For such men, use of the current clinical decision limits for percent fPSA could cause some men with prostate cancer to be misdiagnosed as having benign disease, and therefore fPSA should not be used to diagnose prostate cancer in these patients.
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| 4. |
- Bruun, Laila, et al.
(författare)
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Percent-free prostate specific antigen is elevated in men on haemodialysis or peritoneal dialysis treatment.
- 2003
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Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 1460-2385. ; 18:3, s. 598-602
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Tidskriftsartikel (refereegranskat)abstract
- Background: Men with chronic renal failure evaluated for transplantation are often tested for prostate specific antigen (PSA) to detect prostate cancer. PSA occurs in several different molecular forms in serum: free PSA (fPSA) and complexed PSA (cPSA), the sum of which corresponds to total PSA (tPSA). In addition to tPSA, percent fPSA to tPSA (%fPSA) is widely used to enhance discrimination of benign disorders from prostate cancer. The low molecular mass of fPSA suggests elimination by renal glomerular filtration and that renal failure may significantly influence %fPSA. We evaluated whether established reference levels for %fPSA are applicable also to patients treated with haemodialysis or continuous ambulatory peritoneal dialysis (CAPD).Methods: The study included 20 men on intermittent haemodialysis with low-flux membranes and 25 men on CAPD, without known history of prostate cancer. The control group included 3129 men without known prostate cancer. We analysed fPSA and tPSA in serum by dual-label immunofluorometric assays, from which we calculated %fPSA and cPSA. Serum levels of different PSA forms were adjusted for age and presented as geometric means.Results: Percent fPSA was significantly higher in patients on either haemodialysis (39.5%) or CAPD (39.6%) compared with controls (28.1%). Haemodialysis patients, but not CAPD patients, had significantly higher mean levels of fPSA. Levels of tPSA and cPSA for haemodialysis or CAPD patients did not differ significantly compared with controls.Conclusions: Recommended reference ranges for %fPSA, based on men with normal renal function, do not apply to uraemic men on dialysis. In these men, a high %fPSA should not be considered as a sign of benign disease. This is clinically important in the evaluation of dialysis patients for transplantation, as %fPSA is often used as a tool for detection of prostate cancer.
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| 5. |
- Bruun, Laila, et al.
(författare)
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Rapid elimination by glomerular filtration of free prostate specific antigen and human kallikrein 2 after renal transplantation.
- 2004
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Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 171:4, s. 1432-1435
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The low molecular mass and short half-life of free (f) prostate specific antigen (PSA) implies elimination from blood by glomerular filtration. In addition, patients with terminal renal failure have increased fPSA in serum but there have been sparse data reported on the rates and pathways of elimination of PSA complexes and human kallikrein 2 (hK2). We studied glomerular filtration dependent elimination of fPSA and hK2 in patients with renal insufficiency undergoing successful renal transplantation.MATERIALS AND METHODS: We studied 14 patients with immediate onset of renal function after renal transplantation. Blood samples were obtained before and at regular intervals up to 160 hours after transplanted kidney reperfusion. Measurements of fPSA, total PSA and hK2 were performed with immunofluorometric assays and complexed PSA was determined by a chemiluminiscence assay. Glomerular filtration rates were monitored by analyzing serum creatinine and cystatin C. NONMEM, a multivariate pharmacokinetic approach, was used to determine the elimination rates of fPSA and hK2 after renal transplantation.RESULTS: Serum fPSA and hK2 but not PSA complexes, decreased rapidly after renal transplantation. Significant reductions in fPSA and hK2 were observed after only 16 and 8 hours, respectively. fPSA and hK2 showed similar elimination patterns, decreasing to 42% and 44% of their original levels compared to cystatin C, which was at 44% after 160 hours. The median half-lives of fPSA and hK2 were 17.4 and 11.5 hours, respectively.CONCLUSIONS: These results verify the hypothesis that fPSA and hK2 are eliminated from the blood circulation by glomerular filtration and severe renal failure influences the levels of the 2 proteins in serum.
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| 6. |
- Christensson, Anders, et al.
(författare)
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Intra-individual short-term variability of prostate-specific antigen and other kallikrein markers in a serial collection of blood from men under evaluation for prostate cancer.
- 2011
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Ingår i: BJU International. - 1464-4096. ; 107, s. 1769-1774
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Tidskriftsartikel (refereegranskat)abstract
- Study Type - Diagnostic (exploratory cohort) Level of Evidence 2b OBJECTIVES: To assess variation of total prostate-specific antigen (tPSA), free PSA (fPSA), percent fPSA, human glandular kallikrein 2 (hK2) and intact PSA measured three times within 2 weeks. Knowledge of the variation in an individual's PSA level is important for clinical decision-making. PATIENTS AND METHODS: Study participants were 149 patients referred for prostate biopsy, of which 97 had benign disease and 52 had prostate cancer. Three blood samples were drawn with a median of 4 h between first and second samples and 12 days between first and third samples. Variability was described by absolute differences, ratios and intra-individual coefficients of variation. Total PSA, fPSA, hK2 and intact PSA were measured in anticoagulated blood plasma. RESULTS: At baseline, the median tPSA was 6.8 (interquartile range, 4.5-9.6) ng/mL. The intra-individual variation was low for all biomarkers, and lowest for tPSA. For 80% of participants, the ratio between first and second time points for tPSA was in the range 0.91-1.09 and the ratio for percent fPSA was in the range 0.89-1.15. Total coefficients of variation between time 1 and 2 for tPSA, fPSA, percent fPSA, hK2 and intact PSA were 4.0%, 6.6%, 6.0%, 9.2% and 9.5%, respectively. The measurements taken several days apart varied more than those taken on the same day, although the variation between both time points was not large. CONCLUSIONS: The intra-individual variation for all the kallikrein-like markers studied was relatively small, especially for samples drawn the same day. Few cases are reclassified between the time points. This indicates the high short-term biological and technical reproducibility of the tests in clinical use.
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| 7. |
- Eckersten, Dag, et al.
(författare)
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Anti-Müllerian hormone, a Sertoli cell-derived marker, is decreased in plasma of male patients in all stages of chronic kidney disease.
- 2015
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Ingår i: Andrology. - : Wiley. - 2047-2927 .- 2047-2919. ; 3:6, s. 1160-1164
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Tidskriftsartikel (refereegranskat)abstract
- Male patients with terminal renal failure are often infertile and exhibit an abnormal sex hormone pattern in plasma. We studied patients in all chronic kidney disease (CKD) stages to determine plasma levels of anti-Müllerian hormone (AMH), a Sertoli cell-derived marker, and other sex hormones. Seventy-eight male patients with CKD stages 1-5 and a median age of 40 years (22-50 years), as well as 20 healthy controls with a median age of 37 years (26-44 years), were enrolled. The CKD patients were evenly distributed; 18 with CKD stages 1-2, 19 with CKD stage 3, 19 with CKD stage 4, and 22 with CKD stage 5. Cystatin C, follicle-stimulating hormone, luteinizing hormone, prolactin, sex hormone-binding globulin, testosterone, and AMH levels in plasma were analysed. AMH was analysed using the Ansh Labs UltraSensitive AMH assay. Several changes occurred in plasma levels of sex hormones in male patients with CKD. Plasma AMH levels were lower in CKD stages 1-4 by 30% (p = 0.041) and by 70% (p < 0.001) in CKD stage 5 compared with controls. Plasma luteinizing hormone and prolactin levels were higher and testosterone levels were lower compared with controls. The pathophysiological role of this reduction in AMH is unclear, but can be linked to altered Sertoli cell function.
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| 8. |
- Eckersten, Dag, et al.
(författare)
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Impact of Kidney Transplantation on Reproductive Hormone Levels in Males : A Longitudinal Study
- 2018
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Ingår i: Nephron. - : S. Karger AG. - 1660-8151 .- 2235-3186. ; 138, s. 192-201
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Male patients with end-stage renal disease suffer from sexual disturbances and infertility. Disturbances in the hypothalamic-pituitary-gonadal axis are one of the causes of this. Decreased testosterone synthesis in Leydig cells of the testes and hyperprolactinemia are common. Kidney transplantation, unlike hemodialysis, normalizes these changes. However, how kidney transplantation affects Sertoli cell function is poorly understood. This study is aimed at investigating the changes in fertility-related hormones in men before, during, and after renal transplantation. Methods: This longitudinal and prospective single center study enrolled 12 men undergoing living donor kidney transplantation. Plasma levels of creatinine, cystatin C, and serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, testosterone, sex hormone-binding globulin, inhibin B, and anti-Müllerian hormone (AMH) were assayed at 10 different time points before, during, and after kidney transplantation. Results: A rapid decrease in creatinine and cystatin C levels indicated successful renal transplantation. High pre-transplantation plasma levels of prolactin (mean 516 ± 306 mIE/L) and LH (9.4 ± 4.7 IU/L) were normalized after 7 days (248 ± 161 mIE/L and 6.1 ± 3.1 IU/L, respectively). Testosterone decreased rapidly during transplantation and increased again one week post-transplantation. Sertoli cell-derived hormone inhibin B decreased after transplantation, and there was a small non-significant trend of increased AMH after 12 months. Conclusion: Sertoli cell function, based on AMH and inhibin B levels, does not improve to the same extent or as fast as Leydig cell function after kidney transplantation, as determined by testosterone and LH levels.
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| 9. |
- Eckersten, Dag, et al.
(författare)
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MicroRNA-155 and Anti-Müllerian Hormone : New Potential Markers of Subfertility in Men with Chronic Kidney Disease
- 2017
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Ingår i: Nephron Extra. - : S. Karger AG. - 1664-5529. ; 7:1, s. 33-41
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Men with terminal renal failure are often infertile. Anti-müllerian hormone (AMH), a marker of Sertoli cell function, is decreased among men with chronic kidney disease (CKD). Recently, a microRNA, miR-155, has been shown to be a potential marker for subfertility. We studied miR-155 and semen parameters in patients with CKD who were not yet on dialysis. We also aimed to study possible associations between AMH, miR-155, and semen parameters to evaluate them as markers of fertility. Methods: Thirty male patients with CKD 1–4 as well as 18 healthy controls were enrolled. Results: Serum levels of miR-155 were significantly higher among men with CKD stages 1–2 (4.51 ± 3.81 [p = 0.01]) and stages 3–4 (2.75 ± 1.77 [p = 0.006]) than in controls (1.09 ± 0.44). Sperm concentration was significantly lower among men with CKD 3–4 (42 ± 29) ×106/mL compared to controls (88 ± 42) ×106/mL (p = 0.011). High levels of miR-155 were associated with a relatively low sperm concentration (p = 0.02) and with a low total sperm number (p = 0.005). Low AMH levels were associated with a decreased percentage of motile sperm cells (p = 0.02). Conclusions: We conclude that men with stage 3–4 CKD had lower sperm concentrations than healthy fertile men and that increased serum miR-155 in men with stage 1–4 CKD was associated with semen parameters that indicate subfertility. Low AMH levels were associated with a low percentage of the total number of motile sperm cells. miR-155 and AMH may be potential markers of subfertility in men with CKD.
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| 10. |
- Ristiniemi, Noora, et al.
(författare)
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Evaluation of a new immunoassay for cystatin C, based on a double monoclonal principle, in men with normal and impaired renal function
- 2012
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Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 1460-2385 .- 0931-0509. ; 27:2, s. 682-687
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Tidskriftsartikel (refereegranskat)abstract
- Elevated cystatin C in blood reflects impaired glomerular filtration rate (GFR), but current cystatin C assays, based on polyclonal antibodies and immunoturbidimetric or nephelometric detection, have several limitations. We evaluated a new immunoassay based on monoclonal antibodies in samples from patients with and without chronic kidney disease (CKD). The study enrolled 170 men without known CKD (Group A) and 104 men with CKD (Group B). All patients were assessed with iohexol clearance, plasma creatinine and plasma cystatin C by a conventional particle-enhanced immunoturbidimetric assay (PETIA) and by the new double monoclonal assay. In Group A, three serial blood draws were performed at median intervals of 4 h and 12 days between samples, to also allow assessments of the variability in cystatin C values with the new assay. Concordance correlation coefficients and the 95% limits of agreement were used to estimate the agreement of reciprocal cystatin C and reciprocal creatinine with iohexol clearance. Median iohexol clearance (mL/min/1.73 m(2)) was 81 [interquartile range (IQR) 70, 92] in Group A and 23 (IQR 16, 34) in Group B. The concordance correlation with GFR for the new cystatin C assay compared to the established assay was similar in Group A (0.441 versus 0.465) but higher in Group B (0.680 versus 0.593). Cystatin C measured by both assays exhibited closer agreement with GFR than creatinine. The agreement between the two cystatin C assays was high, with concordance correlations of 0.815 in Group A and 0.935 in Group B. Compared to the conventional assay, the new assay tended to yield lower values of cystatin C at the low end of the range in Group A. The new cystatin C assay exhibited small intraindividual variability across serial samples (coefficient of variation < 6%). In this first clinical evaluation, the new cystatin C assay performed similarly to the established PETIA in patients with normal GFR and better in patients with CKD. The new assay may offer an alternative to current commercial assays to detect and monitor impaired kidney function.
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