| 1. |
- Grubb, Anders, et al.
(author)
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Generation of a new cystatin C-based estimating equation for glomerular filtration rate by use of 7 assays standardized to the international calibrator
- 2014
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In: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 60:7, s. 974-986
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Journal article (peer-reviewed)abstract
- BACKGROUND:Many different cystatin C-based equations exist for estimating glomerular filtration rate. Major reasons for this are the previous lack of an international cystatin C calibrator and the nonequivalence of results from different cystatin C assays.METHODS:Use of the recently introduced certified reference material, ERM-DA471/IFCC, and further work to achieve high agreement and equivalence of 7 commercially available cystatin C assays allowed a substantial decrease of the CV of the assays, as defined by their performance in an external quality assessment for clinical laboratory investigations. By use of 2 of these assays and a population of 4690 subjects, with large subpopulations of children and Asian and Caucasian adults, with their GFR determined by either renal or plasma inulin clearance or plasma iohexol clearance, we attempted to produce a virtually assay-independent simple cystatin C-based equation for estimation of GFR.RESULTS:We developed a simple cystatin C-based equation for estimation of GFR comprising only 2 variables, cystatin C concentration and age. No terms for race and sex are required for optimal diagnostic performance. The equation, [Formula: see text] is also biologically oriented, with 1 term for the theoretical renal clearance of small molecules and 1 constant for extrarenal clearance of cystatin C.CONCLUSIONS:A virtually assay-independent simple cystatin C-based and biologically oriented equation for estimation of GFR, without terms for sex and race, was produced.
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| 2. |
- Malmgren, Linnea, et al.
(author)
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The complexity of kidney disease and diagnosing it - Cystatin C, selective glomerular hypofiltration syndromes and proteome regulation.
- 2023
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In: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 293:3, s. 293-308
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Journal article (peer-reviewed)abstract
- Estimation of kidney function is often part of daily clinical practice, mostly done by using the endogenous GFR-markers creatinine or cystatin C. A recommendation to use both markers in parallel in 2010 has resulted in new knowledge concerning the pathophysiology of kidney disorders by identification of a new set of kidney disorders, selective glomerular hypofiltration syndromes. These syndromes, connected to strong increases in mortality and morbidity, are characterised by a selective reduction in the glomerular filtration of 5-30 kDa molecules, such as cystatin C, compared to the filtration of small molecules < 1kDa dominating the glomerular filtrate e.g., water, urea, creatinine. At least two types of such disorders, shrunken or elongated pore syndrome, are possible according to the pore model for glomerular filtration. Selective glomerular hypofiltration syndromes are prevalent in investigated populations, and patients with these syndromes often display normal measured GFR or creatinine-based GFR-estimates. The syndromes are characterised by proteomic changes promoting the development of atherosclerosis, indicating antibodies and specific receptor-blocking substances as possible new treatment modalities. Presently, the KDIGO guidelines for diagnosing kidney disorders do not recommend cystatin C as a general marker of kidney function and will therefore not allow the identification of a considerable number of patients with selective glomerular hypofiltration syndromes. Furthermore, as cystatin C is uninfluenced by muscle mass, diet or variations in tubular secretion and cystatin C-based GFR-estimation equations do not require controversial race or sex terms, it is obvious that cystatin C should be a part of future KDIGO guidelines.
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| 3. |
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| 4. |
- Christensson, Anders, et al.
(author)
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Serum cystatin C advantageous compared with serum creatinine in the detection of mild but not severe diabetic nephropathy.
- 2004
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In: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 256:6, s. 510-518
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To determine whether serum cystatin C is more accurate than serum creatinine in the detection of diabetic nephropathy, also after adjustment for age.METHODS: Forty-one patients with type 1 and 82 patients with type 2 diabetes were evaluated with serum creatinine, serum cystatin C, and (51)Cr-EDTA clearance (reference method). Cystatin C was measured by a particle-enhanced turbidimetric method and creatinine by an enzymatic method. Statistical estimations were performed both without and with age adjustment created by z-scores for (51)Cr-EDTA clearance, creatinine, and cystatin C. The cut-off levels for glomerular filtration rate (GFR) ((51)Cr-EDTA clearance) were 60 and 80 mL min(-1) 1.73 m(-2), respectively, in absolute values and 80, 90 and 95% CIs, respectively, in age-adjusted values (z-scores).RESULTS: Estimations without age adjustment showed significantly (P = 0.0132) closer correlation for cystatin C (r = 0.817) versus (51)Cr-EDTA clearance as compared with creatinine (r = 0.678). However, when using age-adjusted values, the correlation for cystatin C and creatinine, respectively, versus (51)Cr-EDTA clearance did not differ. When comparing the diagnostic utilities for serum cystatin C versus serum creatinine in manifest renal impairment (GFR < 60 mL min(-1) 1.73 m(-2) or z-scores <-1.28 SD), there were no significant differences between the two markers whether age adjusted or not. However, for diagnosing mild nephropathy (GFR < 80 mL min(-1) 1.73 m(-2) or z-score -0.84 SD), serum cystatin C is significantly more useful.CONCLUSIONS: Serum cystatin C performed better compared with serum creatinine even when measured enzymatically, to detect mild diabetic nephropathy. However, serum creatinine was as efficient as serum cystatin C to detect advanced diabetic nephropathy.
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| 5. |
- Christensson, Anders, et al.
(author)
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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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In: Nephron Physiology. - : S. Karger AG. - 1660-2137. ; 94:2, s. 19-27
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Journal article (peer-reviewed)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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| 6. |
- Christensson, Anders, et al.
(author)
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The shrunken pore syndrome is associated with declined right ventricular systolic function in a heart failure population – the HARVEST study
- 2016
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In: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 76:7, s. 568-574
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Journal article (peer-reviewed)abstract
- The close relationship between heart and kidney diseases was studied with respect to the ‘Shrunken pore syndrome’ that is characterized by a difference in renal filtration between cystatin C and creatinine. Patients were retrieved from the HeARt and brain failure inVESTigation trail (HARVEST) which is an ongoing study undertaken in individuals hospitalized for the diagnosis of heart failure. Ninety-five of 116 patients who underwent transthoracic echocardiograms (TTE) were eligible for this study. We used four different formulas for estimated glomerular filtration rate (eGFR); CKD-EPIcreatinine, CKD-EPIcystatin C, LMrev and CAPA. Presence of the syndrome was defined as eGFR cystatin C ≤ 60% of eGFR creatinine and absence of the syndrome as eGFR cystatin C >90% and <110% of eGFR creatinine. In a linear regression model, adjusted for age and sex, and the ‘Shrunken pore syndrome’ defined by the equation pair CAPA and LMrev and the equation pair CKD-EPIcystatin C and CKD-EPIcreatinine, echocardiographic parameters were studied. The ‘Shrunken pore syndrome’ showed statistically significant associations with measurements of right ventricular (RV) systolic function; (TAPSE and RV S’) (according to the equation pair CKD-EPIcystatin C and CKD-EPIcreatinine). In conclusion, heart failure patients with the ‘Shrunken pore syndrome’ are at increased risk of having RV systolic dysfunction whilst heart failure patients without ‘Shrunken pore syndrome’ seem protected. These findings may indicate common pathophysiological events in the kidneys and the heart explaining the observed increased risk of mortality in subjects with the ‘Shrunken pore syndrome’.
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| 7. |
- Delanaye, Pierre, et al.
(author)
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CKD : A Call for an Age-Adapted Definition
- 2019
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In: Journal of the American Society of Nephrology. - 1046-6673. ; 30:10, s. 1785-1805
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Research review (peer-reviewed)abstract
- Current criteria for the diagnosis of CKD in adults include persistent signs of kidney damage, such as increased urine albumin-to-creatinine ratio or a GFR below the threshold of 60 ml/min per 1.73 m2 This threshold has important caveats because it does not separate kidney disease from kidney aging, and therefore does not hold for all ages. In an extensive review of the literature, we found that GFR declines with healthy aging without any overt signs of compensation (such as elevated single-nephron GFR) or kidney damage. Older living kidney donors, who are carefully selected based on good health, have a lower predonation GFR compared with younger donors. Furthermore, the results from the large meta-analyses conducted by the CKD Prognosis Consortium and from numerous other studies indicate that the GFR threshold above which the risk of mortality is increased is not consistent across all ages. Among younger persons, mortality is increased at GFR <75 ml/min per 1.73 m2, whereas in elderly people it is increased at levels <45 ml/min per 1.73 m2 Therefore, we suggest that amending the CKD definition to include age-specific thresholds for GFR. The implications of an updated definition are far reaching. Having fewer healthy elderly individuals diagnosed with CKD could help reduce inappropriate care and its associated adverse effects. Global prevalence estimates for CKD would be substantially reduced. Also, using an age-specific threshold for younger persons might lead to earlier identification of CKD onset for such individuals, at a point when progressive kidney damage may still be preventable.
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| 8. |
- Fernström, Anders, et al.
(author)
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Achievement of recommended treatment targets for bone and mineral metabolism in haemodialysis patients using paricalcitol : An observational study
- 2011
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In: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 45:3, s. 196-205
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Journal article (peer-reviewed)abstract
- Objective. Secondary hyperparathyroidism (SHPT) is a common problem among patients with chronic kidney disease (CKD) on haemodialysis. This study was conducted to assess the use, effectiveness and safety of intravenous paricalcitol in haemodialysis patients with various degrees of SHPT. Material and methods. This observational, multicentre, prospective study was conducted in 14 Swedish dialysis centres from May 2007 to June 2008 and included 92 haemodialysis patients with a diagnosis of SHPT associated with CKD. The decision to initiate treatment with intravenous paricalcitol was made by the treating physician. No treatment algorithms were provided. Results. Mean patient age was 64 years. Of the 92 patients included, 74 had an intact parathyroid hormone (iPTH) level of > 300 pg/ml at baseline. Median iPTH was 584 pg/ml in patients with a baseline PTH of > 300 pg/ml. During follow-up there was a decrease in iPTH to 323 pg/ml at 6 months (--45%, p < 0.0001). In parallel, there was a small increase in serum calcium, but serum phosphorus and the calcium xx phosphorus product remained unchanged. Conclusions. This study showed that intravenous paricalcitol substantially and safely decreased iPTH in haemodialysis patients with a baseline iPTH above the Kidney Disease Outcomes Quality Initiative recommended target range (150--300 pg/ml) and had minimal impact on serum minerals.
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| 9. |
- Grubb, Anders, et al.
(author)
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Använd ekvationer utan »ras«- termer för att bestämma GFR
- 2022
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In: Läkartidningen. - 0023-7205. ; 119:21212
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Research review (peer-reviewed)abstract
- Glomerular filtration rate (GFR) is estimated by creatinine or cystatin C-based GFR-estimating equations. Those based upon creatinine, but not those based upon cystatin C, use ”race” terms due to that different populations differ in average muscular mass, influencing the creatinine, but not the cystatin C, level. “Race” is not a biological, but a sociological term, determined by self-assesment. New international studies therefore strongly recommend use of cystatin C-based GFR- estimating equations.
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| 10. |
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| 11. |
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| 12. |
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| 13. |
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| 14. |
- Grubb, Anders, et al.
(author)
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Reduction in glomerular pore size is not restricted to pregnant women. Evidence for a new syndrome: 'Shrunken pore syndrome'.
- 2015
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In: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 75:4, s. 333-340
-
Journal article (peer-reviewed)abstract
- The plasma levels of cystatin C, β2-microglobulin, beta-trace protein, retinol binding protein (RBP) and creatinine were determined in plasma samples from 111 randomly selected patients with eGFRcystatin C ≤ 60% of eGFRcreatinine and from 55 control patients with 0.9eGFRcreatinine ≤ eGFRcystatin C ≤ 1.1eGFRcreatinine (eGFRcystatin C ≈ eGFRcreatinine). The concentration ratios of cystatin C/creatinine, β2-microglobulin/creatinine, beta-trace protein/creatinine and RBP/creatinine were significantly higher in patients with eGFRcystatin C ≤ 60% of eGFRcreatinine than in patients with eGFRcystatin C ≈ eGFRcreatinine. When the patients were divided into three groups with different estimated GFR intervals (≤ 40, 40-60 and ≥ 60 mL/min/1.73m(2)) the concentration ratios of cystatin C/creatinine, β2-microglobulin/creatinine, and beta-trace protein/creatinine were significantly higher in patients with eGFRcystatin C ≤ 60% of eGFRcreatinine than in patients with eGFRcystatin C ≈ eGFRcreatinine for all GFR intervals. Similar results were obtained when the population without pregnant women was studied as well as the subpopulations of men or of non-pregnant women. Populations of pre-eclamptic women and pregnant women in the third trimester display similar results. Since the production of these four proteins with sizes similar to that of cystatin C is not co-regulated, the most likely explanation for the simultaneous increase of their creatinine-ratios in patients with eGFRcystatin C ≤ 60% of eGFRcreatinine is that their elimination by glomerular filtration is decreased. We suggest that this is due to a reduction in pore diameter of the glomerular membrane and propose the designation 'Shrunken pore syndrome' for this pathophysiological state.
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| 15. |
- Grubb, Anders, et al.
(author)
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Simple Cystatin C-Based Prediction Equations for Glomerular Filtration Rate Compared with the Modification of Diet in Renal Disease Prediction Equation for Adults and the Schwartz and the Counahan-Barratt Prediction Equations for Children.
- 2005
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In: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 51:8, s. 1420-1431
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Journal article (peer-reviewed)abstract
- BACKGROUND: Serum creatinine is the most commonly used marker for estimation of glomerular filtration rate (GFR). To compensate for its drawbacks as a GFR marker, several prediction equations including several parameters are being used, with the Modification of Diet in Renal Disease (MDRD), Schwartz, and Counahan-Barratt equations being the ones most widely accepted for estimation of relative GFR in mL x min(-1) x (1.73 m(2))(-1). The present study analyzes whether these GFR prediction equations for adults and children might be replaced by simple prediction equations based on plasma concentrations of cystatin C.METHODS: Data from 536 patients (0.3-93 years), consecutively referred for determination of GFR by an invasive gold standard procedure, were used for the analysis. Calculations of bias (median percentage of error), correlation (adjusted R(2)), and percentage of estimates within 30% and 50% of measured GFR were used in the comparisons.RESULTS: A cystatin C-based prediction equation using only concentration in mg/L and a prepubertal factor: GFR [mL x min(-1) x (1.73 m(2))(-1)] = 84.69 x cystatin C (mg/L)(-1.680) x 1.384 (if a child <14 years) assessed GFR equally well or better than the simplified MDRD, the Schwartz, and the Counahan-Barratt prediction equations for the adult (> or =18 years) and juvenile groups of the investigated cohort. Age did not influence the cystatin C-based prediction equation for adults, whereas gender did, but with a factor close to unity (0.948 for females).CONCLUSION: A GFR prediction equation based solely on cystatin C (in mg/L) and a prepubertal factor might replace the simplified MDRD prediction equation for adults and the Schwartz and Counahan-Barratt prediction equations for children.
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| 16. |
- Hobro, Sture, et al.
(author)
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Dialysis as a Novel Adjuvant Treatment for Malignant Cancers
- 2022
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In: Cancers. - : MDPI AG. - 2072-6694. ; 14:20
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Research review (peer-reviewed)abstract
- Cancer metabolism is characterized by an increased utilization of fermentable fuels, such as glucose and glutamine, which support cancer cell survival by increasing resistance to both oxidative stress and the inherent immune system in humans. Dialysis has the power to shift the patient from a state dependent on glucose and glutamine to a ketogenic condition (KC) combined with low glutamine levels—thereby forcing ATP production through the Krebs cycle. By the force of dialysis, the cancer cells will be deprived of their preferred fermentable fuels, disrupting major metabolic pathways important for the ability of the cancer cells to survive. Dialysis has the potential to reduce glucose levels below physiological levels, concurrently increase blood ketone body levels and reduce glutamine levels, which may further reinforce the impact of the KC. Importantly, ketones also induce epigenetic changes imposed by histone deacetylates (HDAC) activity (Class I and Class IIa) known to play an important role in cancer metabolism. Thus, dialysis could be an impactful and safe adjuvant treatment, sensitizing cancer cells to traditional cancer treatments (TCTs), potentially making these significantly more efficient.
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| 17. |
- Lindström, Veronica, et al.
(author)
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Different elimination patterns of beta-trace protein, beta(2)-microglobulin and cystatin C in haemodialysis, haemodiafiltration and haemofiltration.
- 2008
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In: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 68, s. 685-691
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Journal article (peer-reviewed)abstract
- Objective. Low molecular mass proteins (LMMP) are putative uraemic toxins, but their elimination is negligible in standard haemodialysis (HD). In this study, we used beta(2)-microglobulin, cystatin C and beta-trace protein, which differ in molecular mass and charge, to characterize the elimination patterns of three different dialysis modalities. Material and methods. Plasma samples were obtained at the start, 30 min after the start, at the end of the dialysis treatment and 30 min after termination of the dialysis session. Seventeen patients were treated with low-flux HD, 13 with post-dilution haemodiafiltration (HDF) and 8 with pre-dilution haemofiltration (HF). The changes in concentrations of the three LMMPs were monitored and expressed as percentages of the concentrations at the start of treatments. Results. Conventional HD with low-flux membranes showed a high elimination of small molecules (urea and creatinine), but did not reduce the levels of the three LMMPs studied. During HDF and HF, there was a significant decrease in the plasma levels of cystatin C (to 28 % and 44 %, respectively) (p<0.001) and of beta(2)-microglobulin (to 23 % and 33 %, respectively) (p<0.001). However, the level of beta-trace protein was significantly reduced (to 65 %) only after HDF. Conclusions . The three dialysis modalities showed significantly different elimination patterns for the LMMPs studied. Elimination of beta-trace protein was lower than those of cystatin C and beta(2)-microglobulin both in HDF and HF. beta-trace protein was only moderately eliminated by HDF and not at all by HF, and may be a useful marker in the evaluation of different convective therapies.
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| 18. |
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| 19. |
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| 20. |
- Sigurjonsson, Johann, et al.
(author)
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A study of size-selective renal elimination using a novel human model
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In: Scandinavian Journal of Clinical & Laboratory Investigation. - 1502-7686. ; , s. 1-6
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Journal article (peer-reviewed)abstract
- The recently discovered selective glomerular hypofiltration syndromes have increased interest in the actual elimination of molecules in the human kidney. In the present study, a novel human model was introduced to directly measure the single-pass renal elimination of molecules of increasing size. Plasma concentrations of urea, creatinine, C-peptide, insulin, pro-BNP, β2-microglobulin, cystatin C, troponin-T, orosomucoid, albumin, and IgG were analysed in arterial and renal venous blood from 45 patientsundergoing Transcatheter Aortic Valve Implantation (TA VI). The renal elimination ratio (RER) was calculated as the arteriovenous concentration difference divided by the arterial concentration. Estimated glomerular filtration rate (eGFR) was calculated by the CKD-EPI equations for both creatinine and cystatin C. Creatinine (0.11 kDa) showed the highest RER (21.0 ± 6.3%). With increasing molecular size, the RER gradually decreased, where the RER of cystatin C (13 kDa) was 14.4 ± 5.3% and troponin-T (36 kDa) was 11.3 ± 4.6%. The renal elimination threshold was found between 36 and 44 kDa as the RER of orosomucoid (44 kDa) was −0.2 ± 4.7%. The RER of creatinine and cystatin C showed a significant and moderate positive linear relationship with eGFR (r = 0.48 and 0.40). In conclusion, a novel human model was employed to demonstrate a decline in renal elimination with increasing molecularsize. Moreover, RERs of creatinine and cystatin C were found to correlate with eGFR, suggesting the potential of this model to study selective glomerular hypofiltration syndromes.
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| 21. |
- Sällman Almén, Markus, et al.
(author)
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Shrunken Pore Syndrome Is Associated With Increased Levels of Atherosclerosis-Promoting Proteins
- 2019
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In: Kidney International Reports. - : Elsevier BV. - 2468-0249. ; 4:1, s. 67-79
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Journal article (peer-reviewed)abstract
- Introduction: Shrunken pore syndrome (SPS), originally defined by cystatin C-based estimated glomerular filtration rate (eGFRcystatin C) being less than 60% of creatinine-based estimated glomerular filtration rate (eGFRcreatinine) in the absence of extrarenal influences on the plasma levels of cystatin C or creatinine, is associated with a high increase in mortality, even in the absence of reduced glomerular filtration rate (GFR). The objective of the present study was to determine whether the proteome of patients with SPS shows differences from that of patients with normal or reduced measured GFR (mGFR) without SPS.Methods: Four patient cohorts were included: 1 cohort with normal mGFR without SPS, 1 with normal mGFR with SPS, 1 with reduced mGFR without SPS, and 1 with reduced mGFR with SPS. The plasma levels of 177 selected proteins were analyzed.Results: Differences in the levels of 30 proteins were specific for SPS; 31 differences were specific for patients with both SPS and reduced mGFR; and 27 were specific for reduced mGFR. Eighteen of the differences specific for SPS concerned proteins described as promoting, or being associated with, atherosclerosis. Twelve of the differences specific for patients with both SPS and reduced mGFR and 10 of the differences specific for reduced mGFR also concerned proteins described as promoting, or being associated with, atherosclerosis. Almost all (82 of 88) of the concentration differences represented increased levels. For SPS, but not for reduced mGFR, a correlation between protein size and increase in level was observed, with smaller proteins being associated with higher levels.Conclusion: The high mortality in shrunken pore syndrome might be caused by the accumulation of atherosclerosis-promoting proteins in this condition.
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| 22. |
- Xhakollari, Liana, et al.
(author)
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Proteins linked to atherosclerosis and cell proliferation are associated with the shrunken pore syndrome in heart failure patients
- 2021
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In: Proteomics Clinical Applications. - : Wiley. - 1862-8354 .- 1862-8346. ; 15:4
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Journal article (peer-reviewed)abstract
- PURPOSE: The "Shrunken pore syndrome" (SPS) is characterized by a difference in renal filtration between cystatin C and creatinine, resulting in a low eGFRcystatinC /eGFRcreatinine -ratio. Studies have demonstrated a high risk for cardiovascular morbidity and mortality for patients with SPS. In this discovery study, we explored associations between SPS and proteins implicated in cardiovascular disease and inflammation in patients with heart failure.EXPERIMENTAL DESIGN: Plasma samples from 300 individuals in HARVEST-Malmö trial hospitalized for the diagnosis of heart failure (mean age 74.9±11.5 years; 30.0% female), were analyzed with a proximity extension assay consisting of 92 proteins. A Bonferroni-corrected p-value of 0.05/92 = 5.4 × 10-4 was considered significant in the initial age and sex-adjusted analyses. Presence of SPS was defined as eGFRcystatinC ≤60% of eGFRcreatinine .RESULTS: SPS presented with significant associations (p < 5.4 × 10-4 ) in age and sex-adjusted logistic regressions with elevated levels of six proteins; scavenger receptor cysteine rich type 1 protein M130, tumor necrosis factor receptor 1, tumor necrosis factor receptor 2, osteoprotegerin, interleukin-2 receptor subunit alpha, and tyrosine-protein kinase receptor UFO. All proteins remained associated (p < 0.05) with SPS after multivariate adjustments.CONCLUSIONS AND CLINICAL RELEVANCE: In heart failure patients, SPS was associated with proteins linked to atherosclerosis and cell proliferation. This article is protected by copyright. All rights reserved.
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| 23. |
- Xhakollari, Liana, et al.
(author)
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The Shrunken pore syndrome is associated with poor prognosis and lower quality of life in heart failure patients : the HARVEST-Malmö study
- 2021
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In: ESC Heart Failure. - : Wiley. - 2055-5822. ; 8:5, s. 3577-3586
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Journal article (peer-reviewed)abstract
- AIMS: This study aimed to investigate the association between the 'Shrunken pore syndrome' (SPS) and risk of death, 30 day rehospitalization, and health-related quality of life (QoL) in heart failure (HF) patients. SPS is characterized by a difference in renal filtration between cystatin C and creatinine, resulting in a low eGFRcystatin C /eGFRcreatinine ratio.METHODS AND RESULTS: A total of 373 patients hospitalized for HF [mean age 74.8 (±12.1) years; 118 (31.6%) women] were retrieved from the HeARt and brain failure inVESTigation trial (HARVEST-Malmö). Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas were used for estimation of glomerular filtration rate (eGFR). Presence of SPS was defined as eGFRcystatin C ≤ 60% of eGFRcreatinine . In Cox regression multivariate models, associations between SPS, risk of death (median follow-up time 1.8 years), and risk of 30 day rehospitalization were studied. Associations between SPS and impaired QoL were studied using multivariate logistic regressions. In multivariate models, SPS was associated with all-cause mortality [124 events; hazard ratio (HR) 1.99; 95% confidence interval (95% CI) 1.23-3.21; P = 0.005] and with 30 day rehospitalization (70 events; HR 1.82; CI 95% 1.04-3.18; P = 0.036). Analyses of QoL, based on a Kansas City Cardiomyopathy Questionnaire overall score < 50, revealed that SPS was associated with higher risk of low health-related QoL (odds ratios 2.15; CI 95% 1.03-4.49; P = 0.042).CONCLUSIONS: The results of this observational study show for the first time an association between SPS and poor prognosis in HF. Further studies are needed to confirm the results in HF cohorts and experimental settings to identify pathophysiological mechanisms.
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| 24. |
- Åkesson, Anna, et al.
(author)
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Shrunken pore syndrome and mortality : a cohort study of patients with measured GFR and known comorbidities
- 2020
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In: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 80:5, s. 412-422
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Journal article (peer-reviewed)abstract
- Shrunken pore syndrome (SPS) is defined by a cystatin C-based estimation of glomerular filtration rate (eGFRCYS) being less than 60% or 70% of a creatinine-based GFR estimation (eGFRCR) in the absence of extrarenal influences on cystatin C or creatinine concentrations. SPS has been associated with a substantial increase in mortality or morbidity in all investigated populations. However, in these studies, neither the diagnoses, nor causes of death were described, and only estimated GFR was available. The present study concerns 2781 individuals with measured GFR (mGFR), known diagnoses, and known causes of death during 5.6 years in median. Cox multivariate proportional hazards regression model was used to estimate hazard ratios (HR) for all-cause and cancer, cardiovascular, diabetes or chronic kidney disease (CKD) as cause-specific mortality among patients with SPS. At an eGFRCYS/eGFRCR-ratio <0.70, the adjusted SPS death risk in the total cohort (HR 3.0, 95% CI 2.4-3.7) was clearly higher than that for the other diagnosis groups. In a sub-cohort of 1300 persons with or without diagnosis, but with normal mGFR, the all-cause mortality of SPS was markedly increased (HR 4.1, 95% CI 2.6-6.5). In a sub-cohort of 567 persons with normal mGFR and no diagnosis, the all-cause mortality of SPS was even more increased (HR 7.3, 95% CI 2.3-23). The prevalence of SPS in the total cohort was 23% and in the sub-cohorts 17 and 12%, respectively. As SPS is associated with a high mortality, occurs in the absence of reduced mGFR and albuminuria, it expands the spectrum of kidney disorders.
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| 25. |
- Öberg, Carl M., et al.
(author)
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Potential relationship between eGFRcystatin C /eGFRcreatinine -ratio and glomerular basement membrane thickness in diabetic kidney disease
- 2021
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In: Physiological Reports. - : Wiley. - 2051-817X.
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Journal article (peer-reviewed)abstract
- Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease and renal replacement therapy worldwide. A pathophysiological hallmark of DKD is glomeru- lar basal membrane (GBM) thickening, whereas this feature is absent in minimal change disease (MCD). According to fundamental transport physiological principles, a thicker GBM will impede the diffusion of middle-molecules such as cystatin C, potentially leading to a lower estimated GFR (eGFR) from cystatin C compared to that of creatinine. Here we test the hypothesis that thickening of the glomerular filter leads to an increased diffusion length, and lower clearance, of cystatin C. Twenty- nine patients with a kidney biopsy diagnosis of either DKD (n = 17) or MCD (n = 12) were retrospectively included in the study. GBM thickness was measured at 20 sepa- rate locations in the biopsy specimen and plasma levels of cystatin C and creatinine were retrieved from health records. A modified two-pore model was used to simulate the effects of a thicker GBM on glomerular water and solute transport. The mean age of the patients was 52 years, and 38% were women. The mean eGFRcystatin C/ eGFRcreatinine-ratio was 74% in DKD compared to 98% in MCD (p < 0.001). Average GBM thickness was strongly inversely correlated to the eGFRcystatin C/eGFRcreatinine- ratio (Pearson's r = −0.61, p < 0.01). Two-pore modeling predicted a eGFRcystatin C/ eGFRcreatinine-ratio of 78% in DKD. We provide clinical and theoretical evidence sug- gesting that thickening of the glomerular filter, increasing the diffusion length of cys- tatin C, lowers the eGFRcystatin C/eGFRcreatinine-ratio in DKD.
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| 26. |
- Alpkvist, Erik, et al.
(author)
-
Simulation of nitrification of municipal wastewater in moving-bed biofilm process : approach based on a 2D continuum model for growth and detachment
- 2007
-
In: Water Science and Technology. - : Biriwa Education Services. - 0273-1223 .- 1996-9732. ; 55:8-9, s. 247-255
-
Journal article (peer-reviewed)abstract
- This paper presents a complete mathematical model of a Moving Bed biofilm process for waste-water treatment, in particular for the nitrification process. The model is based on a bottom up approach adopting a multidimensional model for the biofilm growth and metabolism and a global mass balance model for the whole reactor. The model shows that oxygen is limiting the amount of biomass involved in the nitrification process. Furthermore, it suggests the existence of an optimal amount biomass for an optimal reactor turnover rate. Studies of two specific new suspended carriers show that the model output is dependable on the geometry of the carrier, and to a satisfactory extent agreeable with measurements.
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| 27. |
- Andersson, Bodil T., et al.
(author)
-
Development and psychometric evaluation of the radiographers’ competence scale
- 2012
-
In: Open Journal of Nursing. - : Scientific Research Publishing, Inc.. - 2162-5336 .- 2162-5344. ; 2:2, s. 85-96
-
Journal article (peer-reviewed)abstract
- Assessing the competence of registered radiographers’ clinical work is of great importance because of the recent change in nursing focus and rapid technological development. Self-assessment assists radiographers to validate and improve clinical practice by identifying their strengths as well as areas that may need to be developed. The aim of the study was to develop and psychometrically test a specially designed instrument, the Radiographers Competence Scale (RCS). A cross sectional survey was conducted comprising 406 randomly selected radiographers all over Sweden. The study consisted of two phases; the development of the instrument and evaluation of its psychometric properties. The first phase included three steps: 1) construction of the RCS; 2) pilot testing of face and content validity; and 3) creation of a web-based 54-item questionnaire for testing the instrument. The second phase comprised psychometric evaluation of construct validity, internal consistency reliability and item reduction. The analysis reduced the initial 54 items of the RCS to 28 items. A logical two-factor solution was identified explaining 53.8% of the total variance. The first factor labelled “Nurse initiated care” explained 31.7% of the total variance. Factor 2 labelled “Technical and radiographic processes” explained 22.1% of the total variance. The scale had good internal consistency reliability, with a Cronbach’s alpha of 0.87. The RCS is a short, easy to administer scale for capturing radiographers’ competence levels and the frequency of using their competence. The scale was found to be valid and reliable. The self-assessment RCS can be used in management, patient safety and quality improvement to enhance the radiographic process.
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| 28. |
- Andersson, Bodil T.
(author)
-
Radiographers’ Professional Competence : Development of a context-specific instrument
- 2012
-
Doctoral thesis (other academic/artistic)abstract
- Aims: The overall aim of this thesis was to explore and describe radiographers‟ professional competence based on patients‟ and radiographers‟ experiences and to develop a context-specific instrument to assess the level and frequency of use of radiographers‟ professional competence.Methods: The design was inductive and deductive. Both qualitative and quantitative methods were used. The data collection methods comprised interviews (Studies I-II) and questionnaires (Studies III-IV). The subjects were patients in study I and radiographers in studies II-IV. In study I, 17 patients were interviewed about their experiences of the encounter during radiographic examinations and treatment. The interviews were analysed using qualitative content analysis. In study II, 14 radiographers were interviewed to identify radiographers‟ areas of competence. The critical incident technique was chosen to analyse the interviews. Studies III and IV were based on a national cross-sectional survey of 406 randomly selected radiographers. Study III consisted of two phases; designing the Radiographer Competence Scale (RCS) and evaluation of its psychometric properties. A 42-item questionnaire was developed and validated by a pilot test (n=16) resulting in the addition of 12 items. Thus the final RCS comprised a 54-item questionnaire, which after psychometric tests was reduced to 28 items. In study IV, the 28-item questionnaire served as data. The level of competencies was rated on a 10-point scale, while their use was rated on a six-point scale.Results: In study I, the female patients‟ comprehensive understanding was expressed as feelings of vulnerability. The encounters were described as empowering, empathetic, mechanical and neglectful, depending on the radiographers‟ skills and attitudes. Study II revealed two main areas of professional competence, direct patient-related and indirect patient-related. The first focused on competencies in the care provided in close proximity to the patient and the second on competencies used in the activities of the surrounding environment. Each of the two main areas was divided into four categories and 31 sub-categories that either facilitated or hindered good nursing care. In study III the analysis condensed the 54-item questionnaire in two steps, firstly by removing 12 items and secondly a further 14 items, resulting in the final 28-item RCS questionnaire. Several factor analyses were performed and a two factor-solution emerged, labelled; “Nurse initiated care” and “Technical and radiographic processes”. The psychometric tests had good construct validity and homogeneity. The result of study IV demonstrated that most competencies in the RCS received high ratings both in terms of level and frequency of use. Competencies e.g. „Adequately informing the patient‟, „Adapting the examination to the patient‟s prerequisites and needs‟ and „Producing accurate and correct images‟ were rated the highest while „Identifying and encountering the patient in a state of shock‟ and „Participating in quality improvement regarding patient safety and care‟ received the lowest ratings. The total score of each of the two dimensions had a low but significant correlation with age and years in present position. The competence level correlated with age and years in present position in both dimensions but not with the use of competencies in the “Nurse initiated care” dimension.Conclusion: This thesis has shown that professional competence is important in the encounter between patient and radiographer. It has also demonstrated that radiographers‟ self-rated professional competence is based on nursing, technological and radiographic knowledge. From a radiographer‟s perspective, „Nurse initiated care‟ and „Technical and Radiographic processes‟ are two core dimensions of Radiographer Competence Scale. The 28-item questionnaire regarding level and frequency of use of competence is feasible to use to measure radiographers‟ professional competence.
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| 29. |
- Andersson, Bodil T., et al.
(author)
-
Radiographers' self-assessed level and use of competencies : a national survey
- 2012
-
In: Insights into Imaging. - : Springer Science and Business Media LLC. - 1869-4101. ; 3:6, s. 635-645
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: To describe radiographers' self-assessed level and use of competencies as well as how sociodemographic and situational factors are associated with these competencies, particularly related to work experience.METHODS: A cross-sectional design was employed. Radiographers (n = 406) completed the self-administered 28-item questionnaire encompassing two dimensions: 'Nurse-initiated care' and 'Technical and radiographic processes'. The level of competencies was rated on a 10-point scale and the frequency of use on a 6-point scale.RESULTS: Most competencies received high ratings both in terms of level and frequency of use. In 'Nurse-initiated care' the competency 'Adequately informing the patient' was rated the highest, while 'Identifying and encountering the patient in a state of shock' and 'Participating in quality improvement regarding patient safety and care' received the lowest ratings. In 'Technical and radiographic processes' the highest rated competencies were 'Adapting the examination to the patient's prerequisites and needs' and 'Producing accurate and correct images'. The lowest frequency of use was 'Preliminary assessment of images'.CONCLUSION: The main findings underline the radiographers' high competency in both 'Nurse-initiated care' and 'Technical and radiographic processes'. The lower rated competencies emphasise the importance of continuous professional education and quality improvement.MAIN MESSAGES :• Assessing radiographers' clinical competencies is fundamental for ensuring professional standards.• Most competencies received high ratings both in the nursing and in the radiographic dimensions.• The highest rated competencies focussed on information and adaptability to the patients needs.• The lowest rated competencies focussed on encountering the patient in shock and image assessments.• Age, years in present position and work place only explained a relatively small part of competency.
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| 30. |
- Bao, Xue, et al.
(author)
-
Complement C3 and incident hospitalization due to chronic kidney disease : a population-based cohort study
- 2019
-
In: BMC Nephrology. - : Springer Science and Business Media LLC. - 1471-2369. ; 20
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Circulating C3 has been associated with diabetes and hypertension, which are the leading causes of chronic kidney disease (CKD). C3 activation is considered to contribute to several renal diseases. Here we examined whether elevated C3 concentration is associated with hospitalization due to CKD in the general population, and whether this relationship is mediated by factors such as diabetes and hypertension. METHODS: Baseline plasma C3 was quantified in 4552 participants, without previous hospital admission due to CKD, from the Malmö Diet and Cancer cohort study. Incidence of first hospitalization due to CKD (main diagnosis) was investigated in relation to C3 levels using Cox proportional hazards regression models after a mean follow-up of 19.2 ± 4.16 years. Traditional risk factors of CKD including diabetes, blood pressure, C-reactive protein and baseline renal function were considered in adjustments and sensitivity analyses. RESULTS: During the follow-up period, 94 subjects were admitted to hospital due to CKD. After multivariate adjustment, the hazard ratios (95% confidence interval) for hospitalization from CKD across quartiles of C3 were 1.00 (reference), 1.68 (0.69, 4.13), 2.71 (1.15, 6.39), and 3.16 (1.36, 7.34) (p for trend = 0.003). Results were generally consistent across different sensitivity analyses. CONCLUSIONS: These findings indicate that C3 is associated with incidence of first hospitalization due to CKD in the general population. The observed relationship cannot be entirely attributed to hyperglycemia and hypertension.
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| 31. |
- Bao, Xue, et al.
(author)
-
Growth differentiation factor-15 and incident chronic kidney disease : a population-based cohort study
- 2021
-
In: BMC Nephrology. - : Springer Science and Business Media LLC. - 1471-2369. ; 22:1
-
Journal article (peer-reviewed)abstract
- Background: The relationship between growth differentiation factor 15 (GDF-15) and the development of chronic kidney disease (CKD) is still unclear. We sought to examine whether plasma GDF-15 was related to incident CKD and kidney function decline using a large prospective cohort study. Methods: 4318 participants of the Malmö Diet and Cancer Study-Cardiovascular Cohort were examined in 1991-1994. Incidence of CKD was followed prospectively by linkage with national patient registers. Estimated glomerular filtration rate (eGFR) was available for all participants at baseline, and was re-measured in a subgroup of 2744 subjects after 16.6 ± 1.49 years. Incidence of CKD was examined in relation to GDF-15 using Cox regression analysis. Logistic regression was used to examine the association of GDF-15 with eGFR change and eGFR-based CKD. Models were carefully corrected for potential confounders including baseline eGFR, N-terminal pro-B-type natriuretic peptide, and competing risk from death. Results: 165 patients developed CKD after 19.2 ± 4.04 years of follow-up. The adjusted hazard ratio (95% confidence interval, CI) for CKD in 4th versus 1st quartile of GDF-15 was 2.37 (1.33, 4.24) (p for trend < 0.01). Each per 1 standard deviation increase in GDF-15 was associated with a decline in eGFR of − 0.97 mL/min/1.73 m2 (95% CI, − 1.49 ~ − 0.45; p < 0.001). GDF-15 was also significantly associated eGFR-based CKD in 2713 subjects with baseline eGFR ≥60 mL/min/1.73 m2. Conclusions: GDF-15 predicted incidence of CKD and eGFR decline in the general population, independent of a wide range of potential risk factors and competing risk of death.
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| 32. |
- Bennet, Louise, et al.
(author)
-
Adult-onset diabetes in Middle Eastern immigrants to Sweden : Novel subgroups and diabetic complications—The All New Diabetes in Scania cohort diabetic complications and ethnicity
- 2021
-
In: Diabetes/Metabolism Research and Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 37:6
-
Journal article (peer-reviewed)abstract
- Background: Middle Eastern immigrants to Europe represent a high risk population for type 2 diabetes. We compared prevalence of novel subgroups and assessed risk of diabetic macro- and microvascular complications between diabetes patients of Middle Eastern and European origin. Methods: This study included newly diagnosed diabetes patients born in Sweden (N = 10641) or Iraq (N = 286), previously included in the All New Diabetes in Scania cohort. The study was conducted between January 2008 and August 2016. Patients were followed to April 2017. Incidence rates in diabetic macro- and microvascular complications were assessed using cox-regression adjusting for the confounding effect of age at onset, sex, anthropometrics, glomerular filtration rate (eGFR) and HbA1c. Findings: In Iraqi immigrants versus native Swedes, severe insulin-deficient diabetes was almost twice as common (27.9 vs. 16.2% p < 0.001) but severe insulin-resistant diabetes was less prevalent. Patients born in Iraq had higher risk of coronary events (hazard ratio [HR] 1.84, 95% CI 1.06–3.12) but considerably lower risk of chronic kidney disease (CKD) than Swedes (HR 0.19; 0.05–0.76). The lower risk in Iraqi immigrants was partially attributed to better eGFR. Genetic risk scores (GRS) showed more genetic variants associated with poor insulin secretion but lower risk of insulin resistance in the Iraqi than native Swedish group. Interpretation: People with diabetes, born in the Middle East present with a more insulin-deficient phenotype and genotype than native Swedes. They have a higher risk of coronary events but lower risk of CKD. Ethnic differences should be considered in the preventive work towards diabetes and its complications.
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| 33. |
- Bruun, Laila, et al.
(author)
-
Assessment of intra-individual variation in prostate-specific antigen levels in a biennial randomized prostate cancer screening program in Sweden.
- 2005
-
In: Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 65:3, s. 216-221
-
Journal article (peer-reviewed)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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| 34. |
- Bruun, Laila, et al.
(author)
-
Increase in percent free prostate-specific antigen in men with chronic kidney disease.
- 2009
-
In: 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
-
Journal article (peer-reviewed)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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| 35. |
- Bruun, Laila, et al.
(author)
-
Percent-free prostate specific antigen is elevated in men on haemodialysis or peritoneal dialysis treatment.
- 2003
-
In: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 1460-2385. ; 18:3, s. 598-602
-
Journal article (peer-reviewed)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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| 36. |
- Bruun, Laila, et al.
(author)
-
Rapid elimination by glomerular filtration of free prostate specific antigen and human kallikrein 2 after renal transplantation.
- 2004
-
In: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 171:4, s. 1432-1435
-
Journal article (peer-reviewed)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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| 37. |
- Buchebner, David, et al.
(author)
-
Longitudinal Assessment of PTH in Community-Dwelling Older Women-Elevations Are Not Associated With Mortality
- 2017
-
In: Journal of the Endocrine Society. - : The Endocrine Society. - 2472-1972. ; 1:6, s. 615-624
-
Journal article (peer-reviewed)abstract
- Context: In older women, the magnitude of elevated parathyroid hormone (PTH) and its consequence is unclear.Objective: To describe normal PTH profiles over time and the association with mortality.Design and Participants: There were 1044 community-dwelling women in the Malmö Osteoporosis Prospective Risk Assessment cohort (OPRA) who attended baseline (age 75 years). Follow-ups were attended by 715 (age 80 years) and 382 (age 85 years).Main Outcome Measures: PTH, estimated glomerular filtration rate (eGFR), 25-hydroxyvitamin D (25OHD) and mortality.Results: At age 75 years, PTH levels for most (n = 877, 88%) were within the normal reference range (NRR) (i.e., <6.9 pmol/L). Longitudinally, between ages 75 and 80 years, PTH increased in 60% of all women (n = 390) but increases of up to 50% above baseline values (64%; n=250) still resulted in PTH levels within the NRR. These women had lower 25OHD levels (74 vs 83 nmol/L, P = 0.001). Only when increases were >50% was PTH elevated beyond the NRR (mean 7.1 ± 3.3). Here, a pronounced decline in eGFR (56 vs 61 mL/min/1.73 m2, P = 0.002) was found, despite no further changes in 25OHD. Extending the observational period until age 85 years gave similar results. Baseline PTH levels above NRR were associated with mortality (hazard ratio, 1.4; 95% confidence interval (CI), 1.1-1.8; P = 0.007), although not after adjustment for covariates (P = 0.082).Conclusions: Most women remained within normal PTH ranges despite large increases of up to 50%. PTH elevated above normal is not independently associated with mortality; impaired kidney function and low 25OHD status may be more prognostic in the very old.
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| 38. |
- Christensson, Anders, et al.
(author)
-
Aortic Stiffness Can be Predicted From Different eGFR Formulas With Long Follow-Up in the Malmö Diet Cancer Study
-
In: Angiology. - 0003-3197. ; , s. 1-9
-
Journal article (peer-reviewed)abstract
- We studied the impact of estimated glomerular filtration rate (eGFR) based on either creatinine or cystatin C, or in combination, on vascular aging (aortic stiffness) and central hemodynamics (central systolic blood pressure) in a Swedish urban population with median 17 years of follow-up. Participants (n = 5049) from the population-based Malmö Diet and Cancer Study that underwent baseline examination and later participated in the prospective cardiovascular arm were selected. Of these, 2064 with measured carotid-femoral pulse wave velocity (cfPWV) and central blood pressure at follow-up were enrolled. eGFR was calculated using cystatin C (eGFRCYS) and creatinine (eGFRCR) equations: Caucasian, Asian, pediatric, and adult cohorts (CAPA), the Lund-Malmö revised (LMrev), and the European Kidney Function Consortium (EKFC) equations. Lower adjusted eGFRCR, but not eGFRCYS, were independently associated with higher cfPWV (P < .001, respectively). eGFR <60 mL/min/1.73 m2 determined higher cfPWV except when using the EKFC equation. Conversely, CAPA/LMrev and CAPA/EKFC ratios were not associated with aortic stiffness. Lower eGFRCR is associated with higher future aortic stiffness independently of age, sex, heart rate, mean blood pressure, body mass index, and antihypertensive treatment. The ratio of eGFRCYS and eGFRCR equations could not predict aortic stiffness at all.
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| 39. |
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| 40. |
- Christensson, Anders, et al.
(author)
-
Association of cancer with moderately impaired renal function at baseline in a large, representative, population-based cohort followed for up to 30 years.
- 2013
-
In: International Journal of Cancer. - : Wiley. - 0020-7136. ; 133:6, s. 1452-1458
-
Journal article (peer-reviewed)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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| 41. |
- CHRISTENSSON, Anders, et al.
(author)
-
Complex formation between protein C inhibitor and prostate‐specific antigen in vitro and in human semen
- 1994
-
In: European Journal of Biochemistry. - : Wiley. - 0014-2956 .- 1432-1033. ; 220:1, s. 45-53
-
Journal article (peer-reviewed)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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| 42. |
- Christensson, Anders, et al.
(author)
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Estimation of the Age-Dependent Decline of Glomerular Filtration Rate from Formulas Based on Creatinine and Cystatin C in the General Elderly Population.
- 2011
-
In: Nephron Clinical Practice. - : S. Karger AG. - 1660-2110. ; 117:1, s. 40-50
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Journal article (peer-reviewed)abstract
- Background/Aims: To evaluate the performance of estimation formulas for glomerular filtration rate (GFR) based on creatinine and cystatin C in elderly. Methods: This study includes 2,931 men and women comprising nine age cohorts (60-93 years) from a longitudinal population-based project in Sweden. The participants were divided into four age groups. GFR was estimated from four formulas: the Modification of Diet in Renal Disease (MDRD), CKD-EPI and Cockroft-Gault (CG) based on creatinine and one based on cystatin C (eGFR-CysC). CG was also adjusted for body surface area (BSA) to CG/BSA. Results: CG, CG/BSA and eGFR-CysC yielded significantly lower GFR values compared to MDRD and CKD-EPI in the oldest persons (>80 years). A low GFR (<30 ml/min/1.73 m(2)) was demonstrated with MDRD in 3.3% (80-89 years) and in 6.3% (>90 years). With CG/BSA it was 8.0% (80-89 years) and 27.2% (>90 years), and with eGFR-CysC it was 12.1% (80-89 years) and 27% (>90 years), respectively. The individual formulas showed different eGFR in the four age cohorts and also different slopes by increasing age. CG/BSA and eGFR-CysC both show steeper declines than MDRD and CKD-EPI. Conclusion: Age-associated decline of renal function is common in elderly and increases immensely after the age of 80 years. More than 25% of the oldest demonstrate eGFR <30 ml/min/1.73 m(2). CG and eGFR-CysC yielded the highest prevalence of decline and MDRD the lowest.
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| 43. |
- Christensson, Anders, et al.
(author)
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Family History of Myocardial Infarction Increases Risk of Renal Dysfunction in Middle Age.
- 2014
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In: American Journal of Nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 39:2, s. 85-91
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Journal article (peer-reviewed)abstract
- Background/Aims: Chronic kidney disease (CKD) is common in the general population, may lead to end-stage renal disease, and is most frequently found among males. Familial clustering of kidney diseases has been observed. We aimed to study a potential association between the family history of myocardial infarction (MI) and renal dysfunction. Methods: 22,297 males and 10,828 females, aged 33-60 years, from a population-based cohort study were studied. Estimated glomerular filtration rate (eGFR) was assessed by the CKD-EPI creatinine equation. Every participant filled in a self-administered questionnaire including family history. Heredity for MI was defined as mother or father having had MI and/or died from MI, and/or brother or sister having had MI. Binary logistic regression and multiple linear regression were used in the analyses. Results: Multiple linear regression revealed a significantly increased risk of renal dysfunction in those with a positive heredity for MI (the whole cohort p = 0.01, males p = 0.000, females p = 0.169). Binary logistic regression showed that males with heredity for MI with a mean age of 43 years have a 2 times higher risk (p = 0.02) of belonging to the group with GFR <45 ml/min/1.73 m(2) compared to those without heredity. For the whole cohort the increased risk was 1.6 times (p = 0.07). There was no significant association for females (p = 0.88). Conclusion: These findings demonstrate that a familial burden of MI is associated with renal dysfunction, in men, already in middle age. Genetic variants may underlie predisposition to CKD in those with heredity for MI. © 2014 S. Karger AG, Basel.
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| 44. |
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| 45. |
- Christensson, Anders, et al.
(author)
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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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In: BJU International. - 1464-4096. ; 107, s. 1769-1774
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Journal article (peer-reviewed)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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| 46. |
- Christensson, Anders
(author)
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Repeatability of FRIM-MAB fire risk index method for multistorey apartment buildings
- 2002
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Reports (other academic/artistic)abstract
- Som en del i utvecklingen av indexmetoden har repeterbarheten hos metoden studerats. Fem ingenjörer har använt indexmetoden för att bedöma fyra olika byggnader. Resultaten presenteras i denna rapport. Dessutom ges förslag till hur metoden kan förbättras bl a genom att nya hjälptexter förs in i metodbeskrivningen.
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| 47. |
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| 48. |
- Christensson, Bertil, et al.
(author)
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Interferon-alpha and ribavirin treatment of hepatitis C in children with malignancy in remission
- 2000
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In: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1537-6591 .- 1058-4838. ; 30:3, s. 585-586
-
Journal article (peer-reviewed)abstract
- Twenty-eight cases of hepatitis C virus (HCV) infection were identified in children in a pediatric oncology ward during 2 nosocomial outbreaks. HCV infection spontaneously cleared in 6 patients (21%). Eleven patients with persistent HCV viremia who had malignant diseases in remission after treatment were given a 48-week course of combined therapy with interferon-alpha (5x106 U 3 times weekly) and oral ribavirin (15 mg/kg/d). Seven (64%) of the 11 patients had sustained virological responses 6 and 12 months after cessation of therapy. Side effects were common but generally were mild or moderate.
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| 49. |
- Christensson, Camilla, et al.
(author)
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Safety of inhaled budesonide: clinical manifestations of systemic corticosteroid-related adverse effects.
- 2008
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In: Drug Safety. - 1179-1942. ; 31:11, s. 965-988
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Journal article (peer-reviewed)abstract
- Inhaled corticosteroid (ICS) therapy is central to the long-term management of asthma and is extensively used in the management of chronic obstructive pulmonary disease (COPD). While administration via inhalation limits systemic exposure compared with oral or injected corticosteroids and, therefore, the risk of systemic corticosteroid-related adverse effects, concerns over the long-term safety of ICS persist. The assessment of the long-term effects of ICS therapy requires considerable research effort over years or even decades. Surrogate markers/predictors for clinical endpoints such as adrenal crisis, reduced final height and fractures have been identified for use in relatively short-term studies. However, the predictive value of such markers remains questionable.Inhaled budesonide has been available since the early 1980s and there is a considerable evidence base investigating the safety of this agent. To assess the long-term safety of inhaled budesonide therapy in terms of the actual incidence of the clinical endpoints adrenal crisis/insufficiency, reduced final height, fractures and pregnancy complications, we undertook a review of the scientific literature. The external databases BIOSIS, Cochrane Central Register of Controlled Trials, Current Contents, EMBASE, International Pharmaceutical Abstracts and MEDLINE were searched, in addition to AstraZeneca's internal product literature database Planet, up to 29 February 2008. Only original articles of epidemiological studies, national surveys, clinical trials and case reports concerning inhaled budesonide were included.Eight surveys of adrenal crisis were found. The only survey with specified criteria for diagnosis involved 2912 paediatricians and endocrinologists and revealed 33 patients with adrenal crisis associated with ICS therapy; only one patient used budesonide (in co-treatment with fluticasone propionate). In addition, 14 case reports of adrenal crisis in budesonide-treated patients were found. In only two of these, budesonide was used at recommended doses and in the absence of interacting medication.Three retrospective studies and one prospective study assessing final height were found. None of them showed any reduced final height in patients receiving inhaled budesonide during childhood or adolescence.Seventeen epidemiological studies investigating the risk of fractures were found. When adjusting for confounding factors, they did not provide any unequivocal data for an increased fracture risk with budesonide. Four prospective placebo-controlled clinical trials of 2-6 years duration with inhaled budesonide in patients with asthma or COPD were found. None of the studies identified any association between inhaled budesonide and increased risk for fractures.Four studies using data from the Swedish birth and health registries showed there was no increased risk for congenital malformations, cardiovascular defects, decreased gestational age, birth weight or birth length among infants born to women using inhaled budesonide during pregnancy compared with the general population. This was confirmed by five observational studies in Australia, Canada, Hungary, Japan and the US. Similarly, one randomized clinical trial comparing pregnancy outcomes among asthma patients receiving inhaled budesonide or placebo did not demonstrate any difference in outcome of pregnancy.In summary, based on 25 years of experience with different doses and in different populations, inhaled budesonide therapy only in very rare cases appears to be associated with an increased risk of adrenal crisis, reduction in final height, increases in the number of fractures or complications during pregnancy.
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| 50. |
- Christensson, S. Anders, 1953-
(author)
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Representations for military decision making
- 2015
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In: 2015 Third World Conference on Complex Systems (WCCS). - Maroccan. ; , s. 52-52
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Conference paper (peer-reviewed)abstract
- Present--‐day warfare often involves planning and execution of operations in complex environments. In order to support military decision making in such environments I argue that the military situation must be represented by six categories of representations. In current practice only two categories are employed. The six categories should be linked to representations of the operational plan and the planning process. By combining the different categories of representations, military decision makers will gain a better understanding of operational areas that hold complex system behaviour.
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