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1.
  • Fall, Tove, 1979-, et al. (författare)
  • Reference Intervals for Fecal Calprotectin in Adults Using Two Different Extraction Methods in the Uppsala-SCAPIS Cohort
  • 2017
  • Ingår i: Clinical Laboratory. - 1433-6510. ; 63:9, s. 1493-1496
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Fecal calprotectin measurement is generally recommended to exclude inflammatory bowel disease (IBD) in patients with suspected IBD. A problem with the fecal calprotectin assays so far has been the rather long test-turnaround times. Recently a particle enhanced turbidimetric immunoassay (PETIA) for fecal calprotectin with assay times of approximately 10 minutes has been introduced on the European market. The aim of this study was to define reference intervals for adults with this new fecal calprotectin PETIA using two different extraction methods. Methods: Samples were collected from 382 healthy individuals from the Swedish CArdioPulmonary bioImage Study (SCAPIS) Uppsala cohort in the age range 50 - 65 years. 202 samples were processed with CALEX® Cap extraction device (BÜHLMANN, Schönenbuch, Switzerland) and 180 samples were extracted using weighed samples. The extracted samples were analyzed on a Mindray BS-380 using the fCal Turbo PETIA reagent (BÜHLMANN). Results: The calculated reference values for the Calex device were < 199 µg/g for the whole cohort, < 184 µg/g for females, and < 215 µg/g for males, while the corresponding values for weighed samples were < 153 µg/g for the whole cohort, < 141 µg/g for females, and < 215 µg/g for males. There were no significant statistical differences for calprotectin levels in males and females. Conclusions: The CALEX device yielded slightly higher calprotectin values. As there were no significant gender differences, the study indicates gender independent reference intervals of < 199 µg/g feces for the CALEX device and < 153 µg/g feces for weighed samples in patients in the 50 - 65 year age range.
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2.
  • Fall, Tove, 1979-, et al. (författare)
  • Reference Intervals for Fecal Calprotectin in Pregnant Women Using a Particle Enhanced Turbidimetric Assay
  • 2019
  • Ingår i: Clinical Laboratory. - 1433-6510. ; 65:7, s. 1293-1297
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Fecal calprotectin is widely used as a marker for inflammatory bowel diseases (IBD). IBD often affects women during their reproductive years, but there are no established reference intervals during pregnancy. The aim of the present study was to define reference values during pregnancy and in the postpartum period to allow comparisons between patient results and reference values.METHODS: Fecal samples were collected from 84 healthy females during pregnancy week 26 to 28 and a second sample was collected six months after delivery. The samples were weighed, extracted, and centrifugated to remove debris. The extracted samples were then analyzed on a chemistry analyzer using a particle enhanced turbidimetric immunoassay reagent.RESULTS: The calculated reference interval during pregnancy was < 127 μg/g (90% confidence interval, 90 - 164 μg/g) and the corresponding reference interval during the postpartum period was < 143 μg/g (60 - 226 μg/g). There were no significant statistical differences between F-calprotectin values analyzed at the two sampling times.CONCLUSIONS: The reference values are slightly higher than the cutoff values of 50 - 100 μg/g often used as General cutoff for fecal calprotectin.
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4.
  • Feldreich, T., et al. (författare)
  • Urinary osteopontin predicts incident chronic kidney disease, while plasma osteopontin predicts cardiovascular death in elderly men
  • 2017
  • Ingår i: CardioRenal Medicine. - : S. Karger AG. - 1664-3828 .- 1664-5502. ; 7:3, s. 245-254
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Objectives: The matricellular protein osteopontin is involved in the pathogenesis of both kidney and cardiovascular disease. However, whether circulating and urinary osteopontin levels are associated with the risk of these diseases is less studied.Design, Setting, Participants, and Measurements: A community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men [ULSAM]; n = 741; mean age: 77 years) was used to study the associations between plasma and urinary osteopontin, incident chronic kidney disease, and the risk of cardiovascular death during a median of 8 years of follow-up.Results: There was no significant cross-sectional correlation between plasma and urinary osteopontin (Spearman ρ = 0.07, p = 0.13). Higher urinary osteopontin, but not plasma osteopontin, was associated with incident chronic kidney disease in multivariable models adjusted for age, cardiovascular risk factors, baseline glomerular filtration rate, urinary albumin/creatinine ratio, and the inflammatory markers interleukin 6 and high-sensitivity C-reactive protein (odds ratio for 1 standard deviation [SD] of urinary osteopontin, 1.42, 95% CI 1.00-2.02, p = 0.048). Conversely, plasma osteopontin, but not urinary osteopontin, was independently associated with cardiovascular death (multivariable hazard ratio per SD increase, 1.35, 95% CI 1.14-1.58, p < 0.001, and 1.00, 95% CI 0.79-1.26, p = 0.99, respectively). The addition of plasma osteopontin to a model with established cardiovascular risk factors significantly increased the C-statistics for the prediction of cardiovascular death (p < 0.002).Conclusions: Higher urinary osteopontin specifically predicts incident chronic kidney disease, while plasma osteopontin specifically predicts cardiovascular death. Our data put forward osteopontin as an important factor in the detrimental interplay between the kidney and the cardiovascular system. The clinical implications, and why plasma and urinary osteopontin mirror different pathologies, remain to be established.
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5.
  • Fellström, Bengt, 1947-, et al. (författare)
  • Associations Between Apolipoprotein A1, High-Density Lipoprotein Cholesterol, and Urinary Cytokine Levels in Elderly Males and Females
  • 2019
  • Ingår i: Journal of Interferon and Cytokine Research. - : Mary Ann Liebert Inc. - 1079-9907 .- 1557-7465. ; 40:2, s. 71-74
  • Tidskriftsartikel (refereegranskat)abstract
    • There exists a close relationship between cardiovascular diseases and chronic kidney disease. Apolipoprotein A1 and high-density lipoprotein (HDL) cholesterol are widely used as cardiovascular risk markers but they also have anti-inflammatory properties. The aim of this study was to investigate any associations between HDL levels and cytokine levels in urine. We randomly selected 90 urine samples from the Prospective Investigation of the Vasculature in Uppsala Seniors Study (41 males and 49 females). The samples were analyzed with 2 multiplex assays, Multiplex Inflammation I and Cardiovascular II kits (Olink Bioscience, Uppsala, Sweden). We analyzed the correlations between 158 cytokines in urine with apolipoprotein A1, HDL cholesterol, apolipoprotein B, and low-density lipoprotein cholesterol. There were strong correlations for apolipoprotein A1 and HDL cholesterol with individual cytokines. After adjustment for multiplicity testing, there were 33 significant correlations between apolipoprotein A1 and cytokine levels and 14 of these were also significantly correlated with HDL cholesterol. The strongest associations were observed for IL-1α, SPON2, RAGE, PAR-1, TRAIL-R2, IL-4RA, TNFRSF11A, and SCF. A total of 28 out of 33 correlations were negative, indicating a negative relationship between apolipoprotein A1 and urinary cytokines. The study shows a negative correlation between apolipoprotein A1 and HDL cholesterol and urinary cytokine levels. The finding is in agreement with the anti-inflammatory properties of HDL.
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6.
  • Helmersson, Johanna, et al. (författare)
  • Lower creatinine concentration values and lower inter-laboratory variation among Swedish hospital laboratories in 2014 compared to 1996 : results from the Equalis external quality assessment program
  • 2019
  • Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 57:6, s. 838-844
  • Tidskriftsartikel (refereegranskat)abstract
    • Background:Creatinine measurement for estimation of glomerular filtration rate (GFR) is a frequently used laboratory test. Differences in analytic creatinine methods have caused large inter-laboratory variation. International and national standardization efforts have been made in the last decade.Methods:This study describes the results of the standardization efforts in Sweden by summarizing data for creatinine concentration in blood plasma in the Equalis quality assessment program during 1996-2014.Results:Non-compensated Jaffe methods dominated in 1996-2001 (91 of 103 laboratories; 90%) and were then gradually replaced by either compensated Jaffe methods or enzymatic creatinine methods. In 2014 a majority of Swedish hospital laboratories (139 of 159; 87%) used enzymatic methods. The reported mean creatinine value by the Swedish laboratories was about 10 mu mol/L higher than the isotope dilution mass spectrometry (IDMS) assured reference value in 2003, but consistent with the reference value from 2009 to 2014. The inter-laboratory CV was 7%-9% for creatinine values until 2007, and thereafter gradually decreased to about 4%-5% in 2014.Conclusions:The introduction of enzymatic methods in Swedish laboratories has contributed to achieving a low inter-laboratory variation. Also, the reported values are lower for enzymatic methods compared to Jaffe methods, and the values obtained with enzymatic methods were consistent with IDMS certified values established at reference laboratories. Thus, many Swedish hospital laboratories reported 10 mu mol/L lower, and more true, creatinine concentrations in 2012 than in 2003, which may cause bias in longitudinal studies.
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7.
  • Helmersson, Johanna, et al. (författare)
  • Reference values for 34 frequently used laboratory tests in 80-year-old men and women
  • 2016
  • Ingår i: Maturitas. - : Elsevier BV. - 0378-5122 .- 1873-4111. ; 92, s. 97-101
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Reference values are usually based on blood samples from healthy individuals in the age range 20-50 years. Most patients seeking health care are older than this reference population. Many reference intervals are age dependent and there is thus a need to have appropriate reference intervals also for elderly individuals.METHODS: We analyzed a group of frequently used laboratory tests in an 80-year-old population (n=531, 266 females and 265 males). The 2.5th and 97.5th percentiles for these markers were calculated according to the International Federation of Clinical Chemistry guidelines on the statistical treatment of reference values.RESULTS: Reference values are reported for serum alanine transaminase (ALT), albumin, alkaline phosphatase, pancreatic amylase, apolipoprotein A1, apolipoprotein B, apolipoprotein B/apolipoprotein A1 ratio, aspartate aminotransferase (AST), AST/ALT ratio, bilirubin, calcium, calprotectin, cholesterol, HDL-cholesterol, creatinine kinase (CK), creatinine, creatinine estimated GFR, C-reactive protein, cystatin C, cystatin C estimated GFR, gamma-glutamyltransferase (GGT), iron, iron saturation, lactate dehydrogenase (LDH), magnesium, phosphate, transferrin, triglycerides, urate, urea, zinc, hemoglobin, platelet count and white blood cell count. The upper reference limit for creatinine and urea was significantly increased while the lower limit for iron and albumin was decreased in this elderly population in comparison with the population in the Nordic Reference Interval Project (NORIP).CONCLUSIONS: Reference values calculated from the whole population and a subpopulation without cardiovascular disease showed strong concordance. Several of the reference interval limits were outside the 90% confidence interval of NORIP.
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8.
  • Helmersson-Karlqvist, Johanna, et al. (författare)
  • Cystatin C-based glomerular filtration rate associates more closely with mortality than creatinine-based or combined glomerular filtration rate equations in unselected patients
  • 2016
  • Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 23:15, s. 1649-1657
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Decreased glomerular filtration rate (GFR) is an important cardiovascular risk factor, but estimated GFR (eGFR) may differ depending on whether it is based on creatinine or cystatin C. A combined creatinine/cystatin C equation has recently been shown to best estimate GFR; however, the benefits of using the combined equation for risk prediction in routine clinical care have been less studied. This study compares mortality risk prediction by eGFR using the combined creatinine/cystatin C equation (CKD-EPI), a sole creatinine equation (CKD-EPI) and a sole cystatin C equation (CAPA), respectively, using assays that are traceable to international calibrators.METHODS AND RESULTS: All patients analysed for both creatinine and cystatin C from the same blood sample tube (n = 13,054) during 2005-2007 in Uppsala University Hospital Laboratory were divided into eGFR risk categories>60, 30-60 and <30 mL/min/1.73 m(2) by each eGFR equation. During follow-up (median 4.6 years), 4398 participants died, of which 1396 deaths were due to cardiovascular causes. Reduced eGFR was significantly associated with death as assessed by all eGFR equations. The net reclassification improvement (NRI) for the combination equation compared with the sole creatinine equation was 0.10 (p < 0.001) for all-cause mortality and 0.08 (p < 0.001) for cardiovascular mortality, indicating improved reclassification. In contrast, NRI for the combination equation, compared with the sole cystatin C equation, was -0.06 (p < 0.001) for all-cause mortality and -0.02 (p = 0.032) for cardiovascular mortality, indicating a worsened reclassification.CONCLUSIONS: In routine clinical care, cystatin C-based eGFR was more closely associated with mortality compared with both creatinine-based eGFR and creatinine/cystatin C-based eGFR.
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9.
  • Helmersson-Karlqvist, Johanna, et al. (författare)
  • Evaluation of Nova StatStrip and FreeStyle Precision Pro blood ketone tests using 3-hydroxybutyrate doped samples
  • 2019
  • Ingår i: Journal of clinical laboratory analysis (Print). - : John Wiley & Sons. - 0887-8013 .- 1098-2825. ; 33:4
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background The most clinically useful blood ketone in the diagnosis, management, and recovery of diabetes ketoacidosis in both adults and children is 3-hydroxybutyrate. In the absence of laboratory routine methods, several point-of-care methods are in use, but very few clinical evaluations are published. Methods This study evaluates linearity and reproducibility of two handheld point-of-care meters for blood 3-hydroxybutyrate measurement for hospital use, Nova StatStrip, and FreeStyle Precision Pro. Whole blood from healthy volunteers was spiked with different concentrations of a 3-hydroxybutyrate solution and tested on the point-of-care instruments. The results were compared with plasma 3-hydroxybutyrate that was analyzed with a laboratory enzymatic end point spectrophotometric reference method. Results Blood 3-hydroxybutyrate on StatStrip was linear with the reference method up to approximately 4 mmol/L, and FreeStyle was linear up to 6 mmol/L. At higher concentrations, the point-of-care instruments gave falsely too low results, especially the StatStrip meter. The FreeStyle meter had better precision and less bias than StatStrip. Conclusion In the acute setting of diabetes ketoacidosis, blood 3-hydroxybutyrate in the higher ranges should be interpreted with caution as the point-of-care meters are less accurate there.
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10.
  • Helmersson-Karlqvist, Johanna, et al. (författare)
  • Prostaglandin F2α formation is associated with mortality in a Swedish community-based cohort of older males
  • 2015
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 36:4, s. 238-243
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: An increasing number of clinical studies highlight the importance of the inflammatory mediator prostaglandin F2α (PGF2α). Prostaglandin F2α activity has been suggested to play pivotal roles in the development of cardiovascular diseases and cancer. However, whether systemic PGF2α concentrations may signal mortality is unknown. The aim was to evaluate in vivo PGF2α formation, by measuring urinary 15-keto-dihydro-PGF2α, and mortality risk in a community setting.METHODS AND RESULTS: Urinary 15-keto-dihydro-PGF2α was measured in a Swedish population of 670 men (aged 77-78 years) and the participants were followed up for a median of 9.7 years (383 died, among them 156 of cardiovascular causes and 102 of cancer). In Cox regression models, urinary 15-keto-dihydro-PGF2α was significantly associated with cardiovascular mortality [multivariate hazard ratio (HR) for 1 SD increase of urinary 15-keto-dihydro-PGF2α: 1.18; 95% CI:1.04-1.34; P = 0.01) independent of established cardiovascular risk factors including C-reactive protein. Urinary 15-keto-dihydro-PGF2α was also independently associated with total mortality (multivariate HR for 1 SD increase of urinary 15-keto-dihydro-PGF2α: 1.11; 95% CI: 1.01-1.21; P = 0.03). The combination of 15-keto-dihydro-PGF2α concentrations above the median and high serum high-sensitive C-reactive protein (>3 mg/L) was independently associated with a two-fold increased risk of cancer and total mortality (P = 0.02 and P < 0.001, respectively).CONCLUSION: This is the first study to show that the inflammatory mediator PGF2α was independently associated with mortality and specifically cardiovascular mortality 10 years later. The results are in line with the emerging evidence of the importance of the inflammatory mediator PGF2α in fatal cardiovascular disease.
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11.
  • Helmersson-Karlqvist, Johanna, et al. (författare)
  • The Roche Immunoturbidimetric Albumin Method on Cobas c 501 Gives Higher Values Than the Abbott and Roche BCP Methods When Analyzing Patient Plasma Samples
  • 2016
  • Ingår i: Journal of clinical laboratory analysis (Print). - : Wiley. - 0887-8013 .- 1098-2825. ; 30:5, s. 677-681
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Serum/plasma albumin is an important and widely used laboratory marker and it is important that we measure albumin correctly without bias. We had indications that the immunoturbidimetric method on Cobas c 501 and the bromocresol purple (BCP) method on Architect 16000 differed, so we decided to study these methods more closely.METHOD: A total of 1,951 patient requests with albumin measured with both the Architect BCP and Cobas immunoturbidimetric methods were extracted from the laboratory system. A comparison with fresh plasma samples was also performed that included immunoturbidimetric and BCP methods on Cobas c 501 and analysis of the international protein calibrator ERM-DA470k/IFCC.RESULTS: The median difference between the Abbott BCP and Roche immunoturbidimetric methods was 3.3 g/l and the Roche method overestimated ERM-DA470k/IFCC by 2.2 g/l. The Roche immunoturbidimetric method gave higher values than the Roche BCP method: y = 1.111x - 0.739, R² = 0.971.CONCLUSION: The Roche immunoturbidimetric albumin method gives clearly higher values than the Abbott and Roche BCP methods when analyzing fresh patient samples. The differences between the two methods were similar at normal and low albumin levels.
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12.
  • Helmersson-Karlqvist, Johanna, et al. (författare)
  • Urinary KIM-1, but not urinary cystatin C, should be corrected for urinary creatinine
  • 2016
  • Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 49:15, s. 1164-1166
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: The interest for tubular damage markers such as urinary cystatin C (U-CystC) and kidney injury molecule-1 (U-KIM-1) grows, especially for the diagnosis of acute kidney injury. The trend to measure proteins in spot urine samples instead of 24-h urine collections calls for adjustment of urine dilution with urinary creatinine (UCr). However, it is not known whether UCr adjustment provides a more true value of basal U-CystC and U-KIM-1 levels than absolute values.DESIGN & METHODS: This study examines the rationale for UCr correction for U-CystC and U-KIM-1 by exploring the linear relations between U-CystC and U-KIM-1 and UCr, respectively, and the biological day to day variation of absolute concentrations and UCr adjusted values of the two biomarkers.RESULTS: Both U-CystC and U-KIM-1 concentrations correlated positively with UCr (R=0.37, P<0.001 and R=0.62, P<0.001, respectively) in 378 participants in a community cohort, which indicated a rationale for adjustment with UCr. However, U-CystC/Cr ratio associated negatively with UCr (R=- 0.31, P<0.001), which could indicate a certain amount of 'over-adjustment'. Morning urine collected for 10 consecutive days from 13 healthy volunteers showed a biological day to day variation of 82% for U-CystC, 75% for U-cystC/Cr ratio, 70% for U-KIM-1 and 46% for U-KIM-1/Cr ratio.CONCLUSIONS: This study supports the use of U-KIM-1/Cr ratio in clinical population studies. Data supporting the use of U-CysC/U-Cr ratio were less convincing and the possible confounding of UCr has to be acknowledged in clinical settings.
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13.
  • Khezri, Banafsheh Seyyed, et al. (författare)
  • Seasonal variability of NT-proBNP in Swedish primary care patients
  • 2017
  • Ingår i: Chronobiology International. - : Taylor & Francis. - 0742-0528 .- 1525-6073. ; 34:10, s. 1473-1477
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to determine if there is a seasonal variation in the widely used heart failure marker NT-proBNP. The study included all primary care requests for NT-proBNP in the county of Uppsala, Sweden, between January 2007 and December 2015. For seasonal variation, the NT-proBNP results for individual months were compared. The NT-proBNP values were highest in July to September, but there was also a minor peak in December-January. In conclusion, a seasonal periodicity for NT-proBNP was demonstrated in primary care patients. The data could be useful for practitioners for evaluation of NT-proBNP results and monitoring of patients with heart failure.
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14.
  • Peura, Sari, et al. (författare)
  • Normal values for calprotectin in stool samples of infants from the population-based longitudinal born into life study
  • 2018
  • Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - Stockholm : Taylor & Francis Group. - 0036-5513 .- 1502-7686. ; 78:1-2, s. 120-124
  • Tidskriftsartikel (refereegranskat)abstract
    • Faecal calprotectin is a protein used as a diagnostic marker for inflammatory bowel diseases. We determined upper limits for normal calprotectin values for neonatal, 6, 12 and 24 months old children using a turbidimetric immunoassay in a cohort of Swedish children. The advantage of the method is that opposite to previously used enzyme-linked immunosorbent assay (ELISA) method, it enables measuring single samples, and thus, shortens the analysis time significantly. There were 72 samples (41.7% female) collected neonatally, 63 samples (34.9% female) at 6 months, 60 samples (40.0% female) at 12 months and 51 samples (43.1% female) at 24 months. The upper limits for normal values were 233, 615, 136 and 57 µg mg-1 for infants aged 0, 6, 12 and 24 months, respectively.
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15.
  • Ridefelt, Peter, et al. (författare)
  • Albumin adjustment of total calcium does not improve the estimation of calcium status
  • 2017
  • Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 77:6, s. 442-447
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There is a longstanding controversy as to whether plasma measurements of total calcium should be adjusted for albumin concentration, and if so which formulas are the most appropriate.Methods: Ionised calcium, total calcium and albumin results, analysed at the same time at Uppsala University Hospital Laboratory between February 2005 and June 2013, were retrieved from a laboratory information system. The dataset included results from 20,003 patients. Total calcium was albumin-modified by a locally derived formula, based on 3106 patients from the dataset, and formulas from the literature. The agreement between the reference method ionised calcium and unadjusted total calcium and the seven different albumin-modifying calcium formulas, respectively, were compared with intra-class correlation coefficients (ICC).Results: Total calcium showed substantial agreement to ionised calcium, ICC 0.85 (95% CI 0.84-0.86) for the whole validation cohort. Albumin-modified calcium by different formulas showed significantly less or equal agreement, however the locally determined formula performed better than formulas taken from the literature. Also, total calcium classified the patient as hypo-normo- or hypercalcemic right in 82% of the patients. The albumin-modified calcium did not classify patients significantly better except in the subgroup hypoalbuminemia (<30g/L) where the local formula classified the patients slightly better than total calcium.Conclusions: Albumin modification of total calcium determinations is unlikely to add valuable information, and this practice should be abandoned. Ionised calcium should be used more frequently when aberrant results for total calcium are followed up, or in patients with known hypoalbuminemia.
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16.
  • Tonkonogi, Aleksandra, et al. (författare)
  • Associations between urinary kidney injury biomarkers and cardiovascular mortality risk in elderly men with diabetes
  • 2016
  • Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 121:3, s. 174-178
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: Three urinary biomarkers, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and cystatin C, have been suggested as clinically relevant highly specific biomarkers of acute kidney tubular damage. Yet, the utility of these biomarkers in the prognostication of diabetic nephropathy has been less studied. Therefore, we aimed to investigate the longitudinal association between these urinary biomarkers and cardiovascular mortality in patients with diabetes.METHODS: The study sample consisted of participants with diabetes in the community-based Uppsala Longitudinal Study of Adult Men (n = 91; mean age 77.8 years). During follow-up (median 8.3 years, interval 0.7-13.4 years), 33 participants died of cardiovascular causes.RESULTS: In a multivariable Cox regression model adjusting for age, glomerular filtration rate, and urinary albumin/creatinine ratio, higher urinary KIM-1/creatinine was associated with an increased risk for cardiovascular mortality (HR per SD increase 1.51, 95% confidence intervals 1.03-2.24, P = 0.03). Neither urinary NGAL/creatinine nor urinary cystatin C/creatinine were independently associated with an increased cardiovascular mortality risk.CONCLUSION: In elderly men with diabetes, higher urinary KIM-1/creatinine was associated with an increased long-term risk of cardiovascular mortality independently of established markers of diabetic nephropathy. Our data provide support for kidney tubular damage as an important aspect of diabetic nephropathy that merits further investigation.
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17.
  • Waikar, Sushrut S, et al. (författare)
  • Relationship of proximal tubular injury to chronic kidney disease as assessed by urinary kidney injury molecule-1 in five cohort studies
  • 2016
  • Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 31:9, s. 1460-1470
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The primary biomarkers used to define CKD are serum creatinine and albuminuria. These biomarkers have directed focus on the filtration and barrier functions of the kidney glomerulus even though albuminuria results from tubule dysfunction as well. Given that proximal tubules make up ∼90% of kidney cortical mass, we evaluated whether a sensitive and specific marker of proximal tubule injury, urinary kidney injury molecule-1 (KIM-1), is elevated in individuals with CKD or with risk factors for CKD.METHODS: We measured urinary KIM-1 in participants of five cohort studies from the USA and Sweden. Participants had a wide range of kidney function and were racially and ethnically diverse. Multivariable linear regression models were used to test the association of urinary KIM-1 with demographic, clinical and laboratory values.RESULTS: In pooled, multivariable-adjusted analyses, log-transformed, creatinine-normalized urinary KIM-1 levels were higher in those with lower eGFR {β = -0.03 per 10 mL/min/1.73 m(2) [95% confidence interval (CI) -0.05 to -0.02]} and greater albuminuria [β = 0.16 per unit of log albumin:creatinine ratio (95% CI 0.15-0.17)]. Urinary KIM-1 levels were higher in current smokers, lower in blacks than nonblacks and lower in users versus nonusers of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.CONCLUSION: Proximal tubule injury appears to be an integral and measurable element of multiple stages of CKD.
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18.
  • Åkerblom, Axel, et al. (författare)
  • Comparison between cystatin C and creatinine estimated GFR in cardiology patients
  • 2015
  • Ingår i: Cardiorenal medicine. - : S. Karger AG. - 1664-5502 .- 1664-3828. ; 5:4, s. 289-296
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Estimation of the glomerular filtration rate (GFR) is essential for identification, evaluation and risk prediction in patients with kidney disease. Estimated GFR (eGFR) is also needed for the correct dosing of drugs eliminated by the kidneys and to identify high-risk individuals in whom coronary angiography or other procedures may lead to kidney failure. Both cystatin C and creatinine are used for the determination of GFR, and we aimed to investigate if eGFR by the two methods differ in cardiology patients. Methods: We compared cystatin C and creatinine (CKD-EPI) eGFR calculated from the same request from a cardiology outpatient unit (n = 2,716), a cardiology ward (n = 980), a coronary care unit (n = 1,464), and an advanced coronary care unit (n = 518) in an observational, cross-sectional study. Results: The median creatinine eGFR results are approximately 10 ml/min/1.73 m2 higher than the median cystatin C eGFR that is up to 90 ml/min/1.73 m2, irrespective of the level of care. Creatinine eGFR resulted in a less advanced eGFR category in the majority of patients with a cystatin C eGFR <60 ml/min/1.73 m2.Conclusions: Our study demonstrates a difference between creatinine and cystatin C eGFR in cardiology patients. It is important to be aware of which marker is used for the reported eGFR to minimize erroneous interpretations of the test results, as this could lead to under- or overmedication. Further studies are needed to determine the best method of estimating the GFR in cardiology units.
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19.
  • Åkerblom, Axel, et al. (författare)
  • Seasonal variations of urate in a Swedish adult population
  • 2017
  • Ingår i: Clinical Rheumatology. - : Springer Science and Business Media LLC. - 0770-3198 .- 1434-9949. ; 36:7, s. 1595-1598
  • Tidskriftsartikel (refereegranskat)abstract
    • Seasonality in the incidence and prevalence of gout has previously been reported but the cause of this seasonality in gout is not explained. The aim of this study was to evaluate possible seasonal variations of urate in a large unselected Swedish adult population. We analyzed 170,915 urate test results from patients at a tertiary care hospital between 2000 and 2016. The results were divided according to sex and sampling month of the year. The median urate values were overall higher in males compared to females and both males and females had peak urate concentrations in the summer months (June-August). There is a seasonal pattern for urate concentrations in a large Swedish population similar to the previously reported seasonality for gout. This may be clinically important and could contribute to the circannual variation of gout. The seasonal pattern should be recognized when evaluating patient results both in clinical practice and in research studies.
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20.
  • Åkerfeldt, Torbjörn, et al. (författare)
  • Postsurgical Acute Phase Reaction is Associated with Decreased Levels of Circulating Myostatin
  • 2015
  • Ingår i: Inflammation. - : Springer Science and Business Media LLC. - 0360-3997 .- 1573-2576. ; 38:4, s. 1727-1730
  • Tidskriftsartikel (refereegranskat)abstract
    • Muscle strength is of importance for postsurgical rehabilitation. Myostatin is a growth factor that regulates the size of muscles and could thus influence muscle mass and function in the postsurgical period. The aim of the present study was to study the changes in myostatin levels during the postsurgical inflammatory period. Myostatin was analysed in serum samples from two elective surgery groups, orthopaedic surgery (n = 24) and coronary bypass patients (n = 21). The samples were collected prior to surgery and 4 and 30 days after surgery. In the orthopaedic group, the median myostatin levels decreased from 3582 ng/L prior to surgery to 774 ng/L at day 4 (p < 0.001) and to 2016 ng/L at day 30 (p < 0.001). Median CRP increased from 2.35 mg/L preoperatively to 117 mg/L at day 4 and decreased to 5.5 mg/L at day 30 in the same group. The coronary bypass group showed a similar pattern with a decrease in myostatin from 4212 ng/L to 2574 ng/L at day 4 (p < 0.001) and to 2808 ng/L at day 30 (p = 0.002). Median CRP increased from 1.80 mg/L preoperatively to 136 mg/L at day 4 and returned to 6.12 mg/L at day 30 in the coronary bypass group. There was a significant decrease in myostatin concentrations both in the early and late postsurgical period. The lowest myostatin concentration time point coincided with the highest CRP concentration time point.
  •  
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