| 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, 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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| 3. |
- 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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| 4. |
- 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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| 7. |
- Christensson, Anders, et al.
(författare)
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Association of cancer with moderately impaired renal function at baseline in a large, representative, population-based cohort followed for up to 30 years.
- 2013
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 133:6, s. 1452-1458
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Tidskriftsartikel (refereegranskat)abstract
- Patients with chronic renal failure show a greater incidence of malignancies. We evaluated whether moderately impaired renal function at baseline influenced risk of all cancers during long-term follow in young persons. Our cohort included 33,346 subjects, aged 26-61 years at baseline, in a representative, population-based study enrolling subjects from 1974 to 1992. Median follow-up time was 28 years. Plasma creatinine was analysed as a single measure at baseline. Incident cases of cancer were identified from the Swedish Cancer Registry. We studied 24,552 subjects from the cohort. To account for the unique sampling design, participants were divided by sex and age at baseline into 1,132 older men (age 60), 14,254 younger men (age 40-52), 7,498 older women (age 47-57) and 1,688 younger women (age 35-43). Glomerular filtration rate (GFR) was estimated using the CKD-EPI formula. Patients were classified as having either normal to mildly impaired kidney function (eGFR≥60 mL/min/1.73m(2) ), or moderate kidney dysfunction (eGFR<60 mL/min/1.73m(2) ). We calculated the risk of all cancers using competing risks regression. Overall, 6,595 participants were diagnosed with cancer, and 854 subjects (3.5%) had moderately impaired renal dysfunction at baseline. There was a significant association between moderately decreased GFR and subsequent risk of kidney cancer in younger men (hazard ratio, 3.38; 95% CI, 1.48 to 7.71; P=0.004). However, we found no association with overall long-term cancer risk. Our confirmation of an association between moderately impaired renal function and risk of kidney cancer in younger men requires further exploration of high-risk groups and biological mechanisms. © 2013 Wiley Periodicals, Inc.
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| 8. |
- CHRISTENSSON, Anders, et al.
(författare)
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Complex formation between protein C inhibitor and prostate‐specific antigen in vitro and in human semen
- 1994
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Ingår i: European Journal of Biochemistry. - : Wiley. - 0014-2956 .- 1432-1033. ; 220:1, s. 45-53
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Tidskriftsartikel (refereegranskat)abstract
- Protein C inhibitor (PCI), a serine‐proteinase inhibitor first purified from human blood plasma, occurs at high concentrations (3–4 μM) in seminal fluid in both a high‐molecular‐mass and low‐molecular‐mass form. Immunochemical data have previously suggested that PCI in seminal plasma forms complexes with the most abundant serine proteinase in semen, prostate‐specific antigen (PSA). To provide a structural characterization of the PCI target, immunodetected as PSA, a procedure was developed to isolate low‐molecular‐mass and high‐molecular‐mass‐forms of PCI from seminal fluid. The high‐molecular‐mass form of PCI, recognized by monoclonal antibodies against PSA, was dissociated by alkaline treatment into the low‐molecular‐mass form of PCI and a 33‐kDa protein identified as PSA by 25 conclusive steps of N‐terminal sequence analysis. We developed a sensitive immunofluorometric assay (IFMA) to measure PCI‐PSA complexes in body fluids and investigated the rate at which purified PSA may form complexes with purified PCI. Formation of complexes detected by this IFMA and the appearance of SDS‐stable approximately 90‐kDa complexes paralleled loss of PSA activity recorded with chromogenic substrates. The rate of complex formation was slow compared to that reported for PCI and activated protein C, but was enhanced up to sixfold in the presence of heparin. Less than 10% of the initial PSA activity remained after 3 h incubation with a sevenfold molar excess of PCI and in the presence of heparin. In freshly collected ejaculates, the rate of PCI‐PSA complex formation measured by IFMA was similar to that observed between the purified proteins, and paralleled the appearance of SDS‐stable complexes by immunoblotting. During gel dissolution in freshly collected ejaculates, approximately 40% of immunodetected PCI becomes complexed to PSA. Although PCI is a slow inhibitor of PSA, complexes between PCI and PSA are detected at levels that correspond to an inactivation of up to 5% of the PSA activity in the ejaculate.
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| 9. |
- 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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| 10. |
- Christensson, Anders, et al.
(författare)
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Serum cystatin C is a more sensitive and more accurate marker of glomerular filtration rate than enzymatic measurements of creatinine in renal transplantation.
- 2003
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Ingår i: Nephron Physiology. - : S. Karger AG. - 1660-2137. ; 94:2, s. 19-27
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background/Aims:</i> Serum creatinine has several drawbacks as marker of glomerular filtration rate (GFR), and therefore serum cystatin C has been proposed as a more optimal GFR marker. Previous reports have suggested benefits of serum cystatin C measurements in patients with renal transplants. The purpose of the present study was to evaluate the diagnostic accuracy of cystatin C measurements compared with enzymatic creatinine measurements as serum markers of GFR (established from plasma clearance of iohexol) in a large cohort of stable renal transplant recipients and in the early postoperative phase. <i>Methods:</i> Renal transplant patients (n = 125) with stable graft function were evaluated from reciprocals of serum creatinine and cystatin C compared with iohexol clearance. Fourteen patients were examined immediately after the onset of renal function. Cystatin C was measured by a particle-enhanced turbidimetric method and creatinine by an enzymatic method. <i>Results:</i> In stable renal transplant recipients, serum cystatin C showed a significantly (p = 0.033) closer correlation (r = 0.89 or 79% co-variance) with iohexol clearance than did serum creatinine (r = 0.81 or 66% co-variance). Using the χ<sup>2</sup> test and a cut-off at 60 ml/min/1.73 m<sup>2</sup>, serum cystatin C levels demonstrated significantly higher sensitivity for early GFR impairment (p = 0.0045) compared with serum creatinine measurements. On the first day after transplantation, serum cystatin C fell more rapidly than serum creatinine. <i>Conclusion:</i> Serum cystatin C levels correlate significantly closer to accurate measurements of GFR and are significantly more sensitive to detect early GFR impairment than enzymatic measurements of creatinine in serum.
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