| 1. |
- Carlsson, Axel C, et al.
(författare)
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Kidney injury molecule (KIM)-1 is associated with insulin resistance : results from two community-based studies of elderly individuals
- 2014
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier. - 0168-8227 .- 1872-8227. ; 103:3, s. 516-21
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Insulin resistance has been shown to be closely associated with glomerular filtration rate and urinary albumin/creatinine ratio, even prior to the development of diabetes. Urinary kidney injury molecule 1 (KIM-1) is a novel, highly specific marker of kidney tubular damage. The role of insulin resistance in the development of kidney tubular damage is not previously reported. Thus, we aimed to investigate the associations between insulin sensitivity (assessed by HOMA) and urinary KIM-1.DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: Two community-based cohorts of elderly individuals were investigated: Prospective Investigation of the vasculature in Uppsala seniors (PIVUS, n=701; mean age 75 years, 52% women); and Uppsala Longitudinal Study of adult men (ULSAM, n=533; mean age 78 years).RESULTS: Lower insulin sensitivity was associated with higher urinary KIM-1 in both cohorts after adjustments for age, BMI, blood pressure, antihypertensive treatment, glomerular filtration rate, and urinary albumin-creatinine ratio (PIVUS: regression coefficient for 1-SD higher HOMA-IR 0.11, 95% CI 0.03-0.20, p=0.009, and ULSAM: 0.13, 95% CI 0.04-0.22, p=0.007). Results were similar in individuals without diabetes, with normal kidney function and normo-albuminuria.CONCLUSIONS: Our findings in elderly individuals support the notion that the interplay between an impaired glucose metabolism and renal tubular damage is evident even prior to the development of diabetes and overt kidney disease.
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| 2. |
- Carlsson, Axel C, et al.
(författare)
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Soluble TNF receptors and kidney dysfunction in the elderly
- 2014
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 25:6, s. 1313-1320
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Tidskriftsartikel (refereegranskat)abstract
- The importance of TNF-α and its soluble receptors (sTNFR1 and sTNFR2) in the development of kidney disease is being unraveled. Yet, community-based data regarding the role of sTNFRs are lacking. We assessed serum sTNFRs and aspects of kidney damage cross-sectionally in two independent community-based cohorts of elderly participants: Prospective Investigation of the Vasculature in Uppsala Seniors (n=815; mean age, 75 years; 51% women) and Uppsala Longitudinal Study of Adult Men (n=778; mean age, 78 years). Serum sTNFR1 correlated substantially with different aspects of kidney pathology in the Uppsala Longitudinal Study of Adult Men cohort (R=-0.52 for estimated GFR, R=0.22 for urinary albumin-to-creatinine ratio, and R=0.17 for urinary kidney injury molecule-1; P<0.001 for all), with similar correlations in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort. These associations remained significant after adjustment for age, sex, inflammatory markers, and cardiovascular risk factors and were also evident in participants without diabetes. Serum sTNFR2 was associated with all three markers in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort (P<0.001 for all). Our findings from two independent community-based cohorts confirm and extend results of previous studies supporting circulating sTNFRs as relevant biomarkers for kidney damage and dysfunction in elderly individuals, even in the absence of diabetes.
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| 3. |
- Carlsson, Axel C, et al.
(författare)
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Urinary kidney injury molecule 1 and incidence of heart failure in elderly men
- 2013
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Ingår i: European Journal of Heart Failure. - : Oxford University Press. - 1388-9842 .- 1879-0844. ; 15:4, s. 447-446
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: There is growing recognition of the clinical importance of cardiorenal syndrome-the bidirectional interplay between kidney and cardiac dysfunction. Yet, the role of kidney tubular damage in the development of heart failure is less studied. The objective of this study was to investigate whether urinary kidney injury molecule (KIM)-1, a specific marker of tubular damage, predisposes to an increased heart failure risk.METHODS AND RESULTS: This was a community-based cohort study [Uppsala Longitudinal study of Adult Men (ULSAM)] of 565, 77-year-old men free from heart failure at baseline. Heart failure hospitalizations were used as outcome. During follow-up (median 8.0 years), 73 participants were hospitalized for heart failure. In models adjusted for cardiovascular risk factors (age, systolic blood pressure, diabetes, smoking, body mass index, LDL/HDL ratio, antihypertensive treatment, lipid-lowering treatment, aspirin treatment, LV hypertrophy, and prevalent cardiovascular disease) and markers of kidney dysfunction and damage [cystatin C-based glomerular filtration rate (GFR) and urinary albumin/creatinine ratio], a higher urinary KIM-1/creatinine ratio was associated with higher risk for heart failure (hazard ratio upper vs. lower tertile, 1.81; 95% confidence interval 1.01-3.29; P < 0.05). Participants with a combination of low GFR (<60 mL/min/1.72 m(2)) and high KIM-1/creatinine (>128 ng/mmol) had a 3-fold increase in heart failure risk compared with participants with normal GFR and KIM-1 (P < 0.001).CONCLUSION: Our findings suggest that kidney tubular damage predisposes to an increased risk for heart failure in the community. Further studies are needed to clarify the causal role of KIM-1 in the development of heart failure, and to evaluate the clinical utility of urinary KIM-1 measurements.
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| 4. |
- Carlsson, Axel C, et al.
(författare)
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Urinary kidney injury molecule-1 and the risk of cardiovascular mortality in elderly men
- 2014
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Ingår i: American Society of Nephrology. Clinical Journal. - 1555-9041 .- 1555-905X. ; 9:8, s. 1393-1401
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Kidney injury molecule-1 (KIM-1) has been suggested as a clinically relevant highly specific biomarker of acute kidney tubular damage. However, community-based data on the association between urinary levels of KIM-1 and the risk for cardiovascular mortality are lacking. This study aimed to investigate the association between urinary KIM-1 and cardiovascular mortality.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a prospective study, using the community-based Uppsala Longitudinal Study of Adult Men (N=590; mean age 77 years; baseline period, 1997-2001; median follow-up 8.1 years; end of follow-up, 2008).RESULTS: During follow-up, 89 participants died of cardiovascular causes (incidence rate, 2.07 per 100 person-years at risk). Models were adjusted for cardiovascular risk factors (age, systolic BP, diabetes, smoking, body mass index, total cholesterol, HDL cholesterol, antihypertensive treatment, lipid-lowering treatment, aspirin treatment, and history of cardiovascular disease) and for markers of kidney dysfunction and damage (cystatin C-based eGFR and urinary albumin/creatinine ratio). Higher urinary KIM-1/creatinine (from 24-hour urine collections) was associated with a higher risk for cardiovascular mortality (hazard ratio per SD increase, 1.27; 95% confidence interval [95% CI], 1.05 to 1.54; P=0.01). Participants with a combination of high KIM-1/creatinine (upper quintile, ≥175 ng/mmol), low eGFR (≤60 ml/min per 1.73 m(2)), and microalbuminuria/macroalbuminuria (albumin/creatinine ratio≥3 g/mol) had a >8-fold increased risk compared with participants with low KIM-1/creatinine (<175 ng/mmol), normal eGFR (>60 ml/min per 1.73 m(2)), and normoalbuminuria (albumin/creatinine ratio<3 g/mol) (hazard ratio, 8.56; 95% CI, 4.17 to 17.56; P<0.001).CONCLUSIONS: These findings suggest that higher urinary KIM-1 may predispose to a higher risk of cardiovascular mortality independently of established cardiovascular risk factors, eGFR, and albuminuria. Additional studies are needed to further assess the utility of measuring KIM-1 in the clinical setting.
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| 5. |
- Fall, Tove, 1979-, et al.
(författare)
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Reference Intervals for Fecal Calprotectin in Adults Using Two Different Extraction Methods in the Uppsala-SCAPIS Cohort
- 2017
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Ingår i: Clinical Laboratory. - 1433-6510. ; 63:9, s. 1493-1496
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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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| 6. |
- Fall, Tove, 1979-, et al.
(författare)
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Reference Intervals for Fecal Calprotectin in Pregnant Women Using a Particle Enhanced Turbidimetric Assay
- 2019
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Ingår i: Clinical Laboratory. - 1433-6510. ; 65:7, s. 1293-1297
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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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| 7. |
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| 8. |
- Fellström, Bengt, 1947-, et al.
(författare)
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Albumin Urinary Excretion Is Associated with Increased Levels of Urinary Chemokines, Cytokines, and Growth Factors Levels in Humans
- 2021
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Ingår i: Biomolecules. - : MDPI. - 2218-273X. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to study the associations between urine albumin excretion, and a large number of urinary chemokines, cytokines, and growth factors in a normal population. We selected 90 urine samples from individuals without CVD, diabetes, stroke or kidney disease belonging to the Prospective Investigation of the Vasculature in Uppsala Seniors Study (41 males and 49 females, all aged 75 years). Urinary cytokine levels were analyzed with two multiplex assays (proximity extension assays) and the cytokine levels were correlated with urine albumin. After adjustment for sex, body mass index (BMI), estimated glomerular filtration rate (eGFR), smoking and multiplicity testing, 11 biomarkers remained significantly associated with urine albumin: thrombospondin 2, interleukin 6, interleukin 8, hepatocyte growth factor, matrix metalloproteinase-12 (MMP-12), C-X-C motif chemokine 9, tumor necrosis factor receptor superfamily member 11B, osteoprotegerin, growth-regulated alpha protein, C-X-C motif chemokine 6, oncostatin-M (OSM) and fatty acid-binding protein, intestinal, despite large differences in molecular weights. In this study, we found associations between urinary albumin and both small and large urine proteins. Additional studies are warranted to identify cytokine patterns and potential progression markers in various renal diseases.
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| 9. |
- Fellström, Bengt, 1947-, et al.
(författare)
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Associations Between Apolipoprotein A1, High-Density Lipoprotein Cholesterol, and Urinary Cytokine Levels in Elderly Males and Females
- 2019
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Ingår i: Journal of Interferon and Cytokine Research. - : Mary Ann Liebert Inc. - 1079-9907 .- 1557-7465. ; 40:2, s. 71-74
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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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| 10. |
- Garcia-Rodriguez, Cruz E., et al.
(författare)
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Does Consumption of Two Portions of Salmon Per Week Enhance the Antioxidant Defense System in Pregnant Women?
- 2012
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Ingår i: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 16:12, s. 1401-1406
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Tidskriftsartikel (refereegranskat)abstract
- Salmon is a rich source of marine n-3 fatty acids, which may increase oxidative stress and, in turn, could affect the antioxidant defense system in blood plasma and erythrocytes of pregnant women. The Salmon in Pregnancy Study provided two meals of salmon per week to pregnant women from week 20 of gestation; the control group maintained their habitual diet low in oily fish. Higher selenium and retinol plasma concentrations were observed after dietary salmon supplementation. Besides, a concomitant increase in selenium and glutathione concentration as well as glutathione peroxidase and reductase activities were detected as pregnancy progressed. However, tocopherols, retinol, beta-carotene, and coenzyme Q(10) decreased in late pregnancy. Collectively, our findings lead to the hypothesis that increased farmed salmon intake may increase antioxidant defenses during pregnancy.
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| 11. |
- Garcia-Rodriguez, Cruz E., et al.
(författare)
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Does Increased Intake of Salmon Increase Markers of Oxidative Stress in Pregnant Women? : The Salmon in Pregnancy Study
- 2011
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Ingår i: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 15:11, s. 2819-2823
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Tidskriftsartikel (refereegranskat)abstract
- The Salmon in Pregnancy Study provided two meals of salmon per week to pregnant women from week 20 of gestation; the control group maintained their habitual diet low in oily fish. Salmon is a rich source of marine n-3 fatty acids. Since marine n-3 fatty acids may increase oxidative stress, we investigated whether increased salmon consumption could affect markers of oxidative stress in mid and late pregnancy. Urinary 8-iso-prostaglandin F(2 alpha), urinary 8-hydroxy-2'-deoxyguanosine, and plasma lipid peroxide concentrations did not change from week 20 to 38 of pregnancy and were not altered by increased consumption of salmon. Thus, increased intake of salmon during pregnancy does not increase oxidative stress, as judged by the markers of oxidative damage to lipids and DNA measured herein.
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| 12. |
- Helmersson-Karlqvist, Johanna, et al.
(författare)
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24-Hour ambulatory blood pressure associates inversely with prostaglandin F-2 alpha, interleukin-6 and F-2-isoprostane formation in a Swedish population of older men
- 2012
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Ingår i: International Journal of Clinical and Experimental Medicine. - 1940-5901. ; 5:2, s. 145-153
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Tidskriftsartikel (refereegranskat)abstract
- Vasoconstrictive prostaglandins (PGs), such as PGF(2 alpha), F-2-isoprostanes, and systemic inflammation may be involved in the physiological regulation of blood pressure (BP) and the pathophysiology leading to hypertension. However, studies evaluating these parameters and BP in human populations are sparse. We analysed the cross-sectional associations between 24-hour ambulatory BP and urinary 15-keto-dihydro-PGF(2 alpha) (indicator of PG-mediated vasoconstriction and inflammation), plasma interleukin-6 (IL-6), C-reactive protein (CRP), serum amyloid A (SAA) and urinary F-2-isoprostanes (indicator of vasoconstriction and oxidative stress) in 619 men in a Swedish older population (Uppsala Longitudinal Study of Adult Men, age 78 years). Both systolic and diastolic 24-hour BP correlated inversely with concentrations of 15-keto-dihydro-PGF(2 alpha) (P < 0.01) and F-2-isoprostanes (P< 0.01) independent on other cardiovascular risk factors. Additionally, diastolic 24-hour BP inversely correlated with plasma IL-6 (P< 0.05) and 24-hour pulse pressure showed a positive linear correlation with IL-6, CRP and SAA. In conclusion, high BP is associated with decreased formation of vasoconstrictive PGF(2 alpha) and F-2-isoprostanes in this population of older men. These findings, although unlike our original hypothesis, might have an important physiological function which needs to be further evaluated.
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| 13. |
- Helmersson-Karlqvist, Johanna, et al.
(författare)
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Association of Test Results for 33 Frequently Used Laboratory Tests with Body Mass Index (BMI)
- 2020
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Ingår i: CLINICAL AND EXPERIMENTAL INVESTIGATIONS. - Lewes. ; 1:1, s. 2-4
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Tidskriftsartikel (refereegranskat)abstract
- Once considered a problem only for high-income countries, obesity rates are now rising worldwide. When evaluating test results from obese patients it is important to be aware of the effect of obesity on individual laboratory test results. The aim of the present study was to study the association between body mass index (BMI) and a group of frequently requested laboratory tests to evaluate which of these analytes that are affected by BMI. We analyzed the association between body mass index (BMI) and Alanine aminotransaminase (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, C-reactive protein, Cystatin C, Gamma-glutamyl transferase (GGT), Iron, Iron saturation, Lactate dehydrogenase (LDH), Magnesium, Phosphate, Transferrin, Triglycerides, Urate, Urea, Zink, Hemoglobin, Platelet count and White blood cell count in an 80-year old population (n=531, 266 females and 265 males). There were significant Spearman rank associations between BMI and laboratory test results for several of the studied markers in both females and males. The strongest associations with BMI were noted for ALT, Apolipoprotein A1, HDL-cholesterol, Hemoglobin, CRP, Cystatin C, Triglycerides and Urate. In conclusion, several of the most frequently used laboratory markers are significantly associated with BMI. To be able to correctly interpret a test result it is important to be aware of the effects of BMI on the test results.
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| 14. |
- Helmersson-Karlqvist, Johanna, et al.
(författare)
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Cystatin C-based glomerular filtration rate associates more closely with mortality than creatinine-based or combined glomerular filtration rate equations in unselected patients
- 2016
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Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 23:15, s. 1649-1657
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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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| 15. |
- Helmersson-Karlqvist, Johanna, et al.
(författare)
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Cytokine mediated inflammation is involved in the early stages of kidney damage and dysfunction
- 2011
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Ingår i: XIII Svenska Kardiovaskulära vårmötet. - Örebro.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Patients with severe chronic kidney disease (CKD) are characterized by increased inflammatory activity and higher oxidative stress, conditions that have been suggested to mediate the substantially increased risk for cardiovascular disease (CVD) in these patients. However, also individuals with mild signs of kidney damage and dysfunction have been shown to have an increased risk for CVD. Yet, data on the association between mild signs of kidney damage and dysfunction and markers of inflammation and oxidative stress in the community is scarce. Research Design and Methods: Accordingly, we investigated the cross-sectional associations between cystatin C based glomerular filtration rate (GFR), urinary albumin creatinine ratio (ACR), and markers of cytokine mediated inflammation (interleukin 6 [IL-6], high sensitivity C reactive protein [hsCRP], serum amyloid A [SAA]), cyclooxygenas-mediated inflammation (urinary prostaglandin F2-alpha [PGF2alpha]) and oxidative stress (urinary F2-isprostanes) in a sub-sample of a community based cohort (Uppsala Longitudinal Study of Adult Men, ULSAM, n=648, mean age 77 year) with normal eGFR (>60 ml/min/1.73m2 ) and normal ACR (<30 µmol/L) Results: In multivariable linear regression models adjusting for age, BMI, smoking, systolic and diastolic blood pressure, total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides and treatment with statin, ACE-inhibit-, ASA-, anti inflammation- , cortisone medication, eGFR was inversely associated with lower hsCRP (p<0.008), lower IL-6 (p<0.01), and ACR was positive associated with higher hsCRP (p=0.01), higher IL-6 (p=<0.004) and higher SAA (p=0.001). No significant association was seen between PGF2alpha, F2-isoprostanes and eGFR and ACR. Conclusion: Our community based data suggest that cytokine mediated inflammation is involved in the early stages of kidney damage and dysfunction, while cyclooxygenas-mediated inflammation and oxidative stress is not. Further studies are needed in order to evaluate to what extent cytokine mediated inflammation mediates the increased CVD risk seen in individuals with mild signs of kidney damage and dysfunction.
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| 16. |
- Helmersson-Karlqvist, Johanna, et al.
(författare)
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Day-to-day variation of urinary NGAL and rational for creatinine correction
- 2013
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Ingår i: Clinical Biochemistry. - : Elsevier. - 0009-9120 .- 1873-2933. ; 46:1-2, s. 70-72
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The number of clinical studies evaluating the new tubular biomarker urinary neutrophil gelatinase-associated lipocalin (U-NGAL) in urine are increasing. There is no consensus whether absolute U-NGAL concentrations or urinary NGAL/creatinine (U-NGAL/Cr) ratios should be used when chronic tubular dysfunction is studied. The aim was to study the biological variation of U-NGAL in healthy subjects and the rational for urinary creatinine (U-Cr) correction in two different study samples.DESIGN AND METHODS: To study biological variation of U-NGAL and U-NGAL/Cr ratio and the association between U-NGAL and U-Cr in healthy subjects 13 young males and females (median age 29years) collected morning urine in 10 consecutive days. Additionally, a random subsample of 400 males from a population-based cohort (aged 78years) collecting 24-hour urine during 1day was studied.RESULTS: The calculated biological variation for absolute U-NGAL was 27% and for U-NGAL/Cr ratio, 101%. Absolute U-NGAL increased linearly with U-Cr concentration (the theoretical basis for creatinine adjustment) in the older males (R=0.19, P<0.001) and with borderline significance in the young adults (R=0.16, P=0.08). The U-NGAL/Cr ratio was, however, negatively associated with creatinine in the older males (R=-0.14, P<0.01) and in the young adults (R=-0.16, P=0.07) indicating a slight "overadjustment."CONCLUSIONS: The study provides some support for the use of U-NGAL/Cr ratio but the rather large biological variation and risk of possible overadjustment need to be considered. Both absolute U-NGAL and U-NGAL/Cr ratios should be reported for the estimation of chronic tubular dysfunction.
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| 17. |
- Helmersson-Karlqvist, Johanna, et al.
(författare)
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Enhanced prostaglandin F(2α) formation in human pregnancy and the effect of increased oily fish intake : Results from the Salmon in Pregnancy Study
- 2012
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Ingår i: Prostaglandins, Leukotrienes and Essential Fatty Acids. - : Elsevier BV. - 0952-3278 .- 1532-2823. ; 86:1-2, s. 35-38
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Tidskriftsartikel (refereegranskat)abstract
- Oily fish intake during pregnancy may reduce the risk of allergic diseases in infancy possibly by shifts in the fatty acid balance and subsequent altered prostaglandin (PG) formation. This intervention is the first study to evaluate if increased oily fish intake affects in vivo PGF(2α) formation during pregnancy. British pregnant women were randomised to two portions of farmed salmon weekly (n=47), or maintenance of their normal diet low in fish (n=41), from pregnancy week 20 until parturition. The concentrations of eicosapentaenoic and docosahexaenoic acids in plasma phosphatidylcholine (PC) were higher and the concentration of arachidonic acid in plasma PC was lower in the salmon group than the control group at weeks 34 and 38 of pregnancy. PGF(2α) formation was evaluated by urinary measurement of 15-keto-dihydro-PGF(2α), a major PGF(2α) metabolite, at 20, 34 and 38 weeks. In both the salmon and control groups urinary 15-keto-dihydro-PGF(2α) concentrations increased significantly during pregnancy, which may be of physiological importance. Oily fish intervention altered fatty acid concentrations but did not affect urinary 15-keto-dihydro-PGF(2α) concentrations in pregnant women.
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| 18. |
- Helmersson-Karlqvist, Johanna, et al.
(författare)
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Evaluation of Nova StatStrip and FreeStyle Precision Pro blood ketone tests using 3-hydroxybutyrate doped samples
- 2019
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Ingår i: Journal of clinical laboratory analysis (Print). - : John Wiley & Sons. - 0887-8013 .- 1098-2825. ; 33:4
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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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| 19. |
- Helmersson-Karlqvist, Johanna, et al.
(författare)
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Evaluation of the Alere D-dimer test for point of care testing
- 2014
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 0929-5305 .- 1573-742X. ; 38:2, s. 250-252
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Tidskriftsartikel (refereegranskat)abstract
- The primary care regularly sees patients that have symptoms that could be due to thromboembolic diseases. It would be valuable to be able to rule out deep venous thrombosis or pulmonary embolism using Wells score and a negative D-dimer testing already at the primary care unit. This requires a validated D-dimer assay suitable for primary care use. We compared D-dimer results obtained with the new point of care analyzer Alere Triage(®) and the central hospital laboratory STA-R Evolution analyzer from the same patient samples (n = 102). We also calculated the total coefficient of variation (CV) for the Alere method. The two methods showed a good linear correlation (R(2) = 0.977) and a slope of 0.975. CV for the Alere D-dimer method was well below 10 %. The study shows that the Alere D-dimer assay and the central laboratory standard assay show similar results. We suggest that the Alere D-dimer assay could be used in primary care in combination with Wells score to reduce referrals to the emergency unit.
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| 20. |
- Helmersson-Karlqvist, Johanna, et al.
(författare)
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Increased urinary cystatin C indicated higher risk of cardiovascular death in a community cohort
- 2014
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 234:1, s. 108-113
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Urinary cystatin C (u-CysC) is a new biomarker for acute tubular kidney dysfunction and may also indicate chronic tubular dysfunction. Chronic kidney disease is an important cardiovascular risk factor, however it is not known if u-CysC is a risk marker for cardiovascular death.METHODS: The association between u-CysC and cardiovascular mortality was investigated in a Swedish community-based cohort of 604 men aged 78 years. During follow-up (mean 6.7 years), 203 participants died, of which 90 due to cardiovascular causes.RESULTS: High u-CysC (>0.029 mg/mmol Cr) was associated with a more than 2-fold risk of cardiovascular death (multivariable hazard ratio for quintile 5 vs. 1: 2.5, 95% CI 1.2-5.2, P < 0.05) in Cox regression models independent of cardiovascular risk factors, glomerular filtration rate (eGFR) and urinary Albumin. Participants with low eGFR (≤60 mL/min), albuminuria (≥3 mg/mmol Cr) and high u-CysC (>0.029 mg/mmol Cr) combined had a significantly higher cardiovascular mortality risk compared to participants with one or two of these biomarkers normal (hazard ratio 15, 95% CI: 6.7-36, P < 0.001, compared to all three biomarkers normal).CONCLUSIONS: This study is the first to show that increased concentrations of the tubular kidney biomarker u-CysC indicated risk of cardiovascular death independently of other cardiovascular risk factors, glomerular filtration and albuminuria. Additional research is needed to further establish the usefulness of u-CysC in clinical practice.
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| 21. |
- Helmersson-Karlqvist, Johanna, et al.
(författare)
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Prostaglandin F2α formation is associated with mortality in a Swedish community-based cohort of older males
- 2015
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 36:4, s. 238-243
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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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| 22. |
- Helmersson-Karlqvist, Johanna, et al.
(författare)
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Serum MMP-9 and TIMP-1 concentrations and MMP-9 activity during surgery-induced inflammation in humans
- 2012
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 50:6, s. 1115-1119
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Tidskriftsartikel (refereegranskat)abstract
- Background: Matrix metalloproteinase 9 (MMP-9) and the endogenous inhibitor to MMP-9, tissue inhibitor of metalloproteinase 1 (TIMP-1), have important roles in tissue remodelling and are implicated in a number of diseases related to inflammation. The time course in activation and formation of MMPs and TIMPs during an inflammatory reaction is not fully known. This study investigates MMP-9 and TIMP-1 concentrations and MMP-9 activity at different time points after major surgery when a state of noticeable inflammation is expected. Methods: Serum MMP-9 and TIMP-1 concentrations and MMP-9 activity were analysed preoperatively and 4 and 30 days postoperatively in patients undergoing elective surgery (coronary artery bypass n=21; orthopaedic surgery, n=29). Results: Serum TIMP-1 and MMP-9 activity increased significantly 4 days after surgery (p<0.05 and p<0.01, respectively) and decreased again 30 days after surgery (p<0.01, respectively, compared to 4 days after surgery). Serum MMP-9 increased significantly 4 days after surgery (p<0.05) and was still high 30 days after surgery (p<0.01 compared to before surgery). The calculated MMP-9/TIMP-1 ratio was increased 30 days after surgery compared to before surgery (p<0.01). Conclusions: The inflammatory state induced by elective surgery is associated with increased TIMP-1 response and MMP-9 activity in serum within a few days which may be of importance for the postoperative heeling process. The further increase in MMP-9 concentrations at day 30 postoperative did not result in increased MMP-9 activity. Serum MMP-9 concentrations or the calculated MMP-9/TIMP-1 ratio do not entirely represent MMP-9 activity during surgery-induced inflammation.
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| 23. |
- Helmersson-Karlqvist, Johanna, et al.
(författare)
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The age related association is more pronounced for cystatin C estimated GFR than for creatinine estimated GFR in primary care patients
- 2013
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 46:16-17, s. 1761-1763
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesThere is an age associated change in GFR but this association may be influenced by the method used. The aims of the present study were to assess the association between age and cystatin C and creatinine based glomerular filtration rate estimates in primary care patients, and to determine the proportion of patients with clinically important renal impairment.Materials and methods1552 samples with simultaneous requests for creatinine and cystatin C from 1552 primary care patients in the county of Uppsala, Sweden were analysed. MDRD, CKD-EPI and cystatin C equations were used to calculate glomerular filtration rate (GFR) and the associations between GFR and age were explored.ResultsThe yearly change in cystatin C estimated GFR was 1.24 mL/min/1.73 m2 while the corresponding decline for creatinine estimated GFR was 0.76 mL/min/1.73 m2 for MDRD and 0.99 mL/min/1.73 m2 for CKD-EPI.ConclusionsThe age related association with GFR estimates is smaller for creatinine estimates than for cystatin C estimates. This leads to differences in the number of patients with reduced eGFR detected with the three estimates and the patient treatment will depend on the estimate used. This is not coherent with a good patient care and we thus need to develop new eGFR equations with better agreement between the estimates.
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| 24. |
- Helmersson-Karlqvist, Johanna, et al.
(författare)
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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
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Ingår i: Journal of clinical laboratory analysis (Print). - : Wiley. - 0887-8013 .- 1098-2825. ; 30:5, s. 677-681
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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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| 25. |
- Helmersson-Karlqvist, Johanna, et al.
(författare)
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Urinary KIM-1, but not urinary cystatin C, should be corrected for urinary creatinine
- 2016
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 49:15, s. 1164-1166
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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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