| 1. |
- Basu, Samar, et al.
(author)
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Cytokine-mediated inflammation is independently associated with insulin sensitivity measured by the euglycemic insulin clamp in a community-based cohort of elderly men
- 2011
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In: International Journal of Clinical and Experimental Medicine. - : E-Century Publishing. - 1940-5901. ; 4:2, s. 164-168
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Journal article (peer-reviewed)abstract
- Both clinical and experimental studies suggest a close relation between an inflammatory state and insulin resistance. We investigated the association between cytokine-mediated inflammation (high sensitivity C reactive protein [hsCRP] and interleukin [IL] 6) and insulin sensitivity (insulin-mediated glucose disposal rate, assessed by the euglycemic insulin clamp) in a community-based cohort, with subgroup analyses of normal weight individuals without diabetes mellitus and metabolic syndrome (NCEP). hsCRP and IL- 6 were inversely associated with insulin sensitivity (multivariable-adjusted regression coefficient for 1-SD increase of hsCRP -0.12 (-0.21-(-0.03), p=0.01) and of IL-6 - 0.11 (-0.21-(-0.02), p=0.01) in models adjusting for age and components of the metabolic syndrome (systolic and diastolic blood pressure, antihypertensive drugs, HDL-cholesterol, triglycerides, fasting plasma glucose, waist circumference). The multivariable-adjusted association between hsCRP, IL-6 and insulin sensitivity were of a similar magnitude in normal weight individuals without diabetes and without the metabolic syndrome. Our data show that cytokine -mediated subclinical inflammation is independently associated with decreased insulin sensitivity also in apparently metabolically healthy normal weight individuals, indicating that the interplay between inflammatory processes and insulin resistance is present already in the early stages of the development of glucometabolic disease. (IJCEM1012002).
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| 2. |
- Carlsson, Axel C, et al.
(author)
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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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In: Diabetes Research and Clinical Practice. - : Elsevier. - 0168-8227 .- 1872-8227. ; 103:3, s. 516-21
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Journal article (peer-reviewed)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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| 3. |
- Carlsson, Axel C, et al.
(author)
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Soluble TNF receptors and kidney dysfunction in the elderly
- 2014
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In: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 25:6, s. 1313-1320
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Journal article (peer-reviewed)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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| 4. |
- Carlsson, Axel C, et al.
(author)
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Urinary kidney injury molecule 1 and incidence of heart failure in elderly men
- 2013
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In: European Journal of Heart Failure. - : Oxford University Press. - 1388-9842 .- 1879-0844. ; 15:4, s. 447-446
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Journal article (peer-reviewed)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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| 5. |
- Carlsson, Axel C, et al.
(author)
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Urinary kidney injury molecule-1 and the risk of cardiovascular mortality in elderly men
- 2014
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In: American Society of Nephrology. Clinical Journal. - 1555-9041 .- 1555-905X. ; 9:8, s. 1393-1401
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Journal article (peer-reviewed)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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| 6. |
- Garcia-Rodriguez, Cruz E., et al.
(author)
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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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In: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 16:12, s. 1401-1406
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Journal article (peer-reviewed)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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| 7. |
- Garcia-Rodriguez, Cruz E., et al.
(author)
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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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In: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 15:11, s. 2819-2823
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Journal article (peer-reviewed)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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| 8. |
- Helmersson-Karlqvist, Johanna, et al.
(author)
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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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In: International Journal of Clinical and Experimental Medicine. - 1940-5901. ; 5:2, s. 145-153
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Journal article (peer-reviewed)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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| 9. |
- Helmersson-Karlqvist, Johanna, et al.
(author)
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Cytokine mediated inflammation is involved in the early stages of kidney damage and dysfunction
- 2011
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In: XIII Svenska Kardiovaskulära vårmötet. - Örebro.
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Conference paper (other academic/artistic)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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| 10. |
- Helmersson-Karlqvist, Johanna, et al.
(author)
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Day-to-day variation of urinary NGAL and rational for creatinine correction
- 2013
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In: Clinical Biochemistry. - : Elsevier. - 0009-9120 .- 1873-2933. ; 46:1-2, s. 70-72
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Journal article (peer-reviewed)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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| 11. |
- Helmersson-Karlqvist, Johanna, et al.
(author)
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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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In: Prostaglandins, Leukotrienes and Essential Fatty Acids. - : Elsevier BV. - 0952-3278 .- 1532-2823. ; 86:1-2, s. 35-38
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Journal article (peer-reviewed)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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| 12. |
- Helmersson-Karlqvist, Johanna, et al.
(author)
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Evaluation of the Alere D-dimer test for point of care testing
- 2014
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In: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 0929-5305 .- 1573-742X. ; 38:2, s. 250-252
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Journal article (peer-reviewed)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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| 13. |
- Helmersson-Karlqvist, Johanna, et al.
(author)
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Increased urinary cystatin C indicated higher risk of cardiovascular death in a community cohort
- 2014
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In: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 234:1, s. 108-113
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Journal article (peer-reviewed)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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| 14. |
- Helmersson-Karlqvist, Johanna, et al.
(author)
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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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In: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 50:6, s. 1115-1119
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Journal article (peer-reviewed)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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| 15. |
- Helmersson-Karlqvist, Johanna, et al.
(author)
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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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In: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 46:16-17, s. 1761-1763
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Journal article (peer-reviewed)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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| 16. |
- Helmersson-Karlqvist, Johanna, et al.
(author)
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Urinary neutrophil gelatinase-associated lipocalin (NGAL) is associated with mortality in a community-based cohort of older Swedish men
- 2013
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In: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 227:2, s. 408-413
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Journal article (peer-reviewed)abstract
- Objective: Neutrophil gelatinase-associated lipocalin (NGAL) indicates tubular kidney damage, neutrophil activation and possibly atherogenesis, however the prospective association between urinary NGAL (u-NGAL) and cardiovascular death in the community is not known.Methods: This study evaluates the association between urinary and serum NGAL and mortality in a Swedish population of 597 men aged 78 years. During the study (median follow-up 8.1 years) 261 men died, 90 of cardiovascular causes.Results: U-NGAL was associated with increased all-cause and cardiovascular mortality (HR 2.0 for quartile 4 vs. quartile 1, 95% CI 1.0-4.0, P < 0.05) in Cox regression models independently of cardiovascular risk factors, CRP and cystatin C estimated glomerular filtration rate (eGFR(CysC)) but not urinary Albumin (u-Alb). A combination of low eGFR(CysC) (<= 60 mL/min), high u-Alb (>= 3 mg/mmol Cr) and high u-NGAL (>= 1.19 mu g/mmol Cr) was associated with a 9-fold increased cardiovascular mortality (P < 0.001) and a 3-fold increased all-cause mortality (P < 0.001). Serum NGAL was associated with increased all-cause mortality risk independent of other cardiovascular risk factors (HR 1.4 for quartile 4 vs. 1, 95% CI 1.0-1.9, P < 0.05) but not after adjustment with CRP, eGFR(CysC) or u-Alb.Conclusion: This community study is the first to show that the tubular kidney biomarker u-NGAL associated with increased cardiovascular and all-cause mortality independent of cardiovascular risk factors and glomerular filtration. Additional research is needed to evaluate the utility of NGAL in clinical practice. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
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| 17. |
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| 18. |
- Jobs, Elisabeth, et al.
(author)
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Serum cathepsin S is associated with serum C-reactive protein and interleukin-6 independently of obesity in elderly men
- 2010
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 95:9, s. 4460-4464
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Cathepsin S has been suggested provide a mechanistic link between obesity and atherosclerosis, possibly mediated via adipose tissue-derived inflammation. Previous data have shown an association between circulating cathepsin S and inflammatory markers in the obese, but to date, community-based reports are lacking. Accordingly, we aimed to investigate the association between serum levels of cathepsin S and markers of cytokine-mediated inflammation in a community-based sample, with prespecified subgroup analyses in nonobese participants. METHODS: Serum cathepsin S, C-reactive protein (CRP), and IL-6 were measured in a community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men; mean age 71 years, n = 991). CRP and IL-6 were also measured at a reexamination after 7 yr. RESULTS: After adjustment for age, body mass index, fasting plasma glucose, diabetes treatment, systolic blood pressure, diastolic blood pressure, hypertension treatment, serum cholesterol, serum high-density lipoprotein cholesterol, prior cardiovascular disease, smoking, and leisure time physical activity, higher cathepsin S was associated with higher CRP (regression coefficient for 1 sd increase, 0.13; 95% confidence interval 0.07-0.19; P < 0.001) and higher serum IL-6 (regression coefficient for 1 sd increase, 0.08; 95% confidence interval 0.01-0.14; P = 0.02). These associations remained similar in normal-weight participants (body mass index <25 kg/m(2), n = 375). In longitudinal analyses, higher cathepsin S at baseline was associated with higher serum CRP and IL-6 after 7 yr. CONCLUSIONS: These results provide additional evidence for the interplay between cathepsin S and inflammatory activity and suggest that this association is present also in normal-weight individuals in the community.
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| 19. |
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| 20. |
- Khezri, Banafsheh, et al.
(author)
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Estimation of the possible economic effects of a sequential testing strategy with NT-proBNP before echocardiography in primary care
- 2014
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In: Clinical Laboratory. - 1433-6510. ; 60:7-8, s. 881-886
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Journal article (peer-reviewed)abstract
- BACKGROUND:The object of the study was to estimate the possible economic effects of a sequential testing strategy with NT-proBNP from a primary care payer perspective.METHODS:The study data were collected from primary care physicians in the County of Uppland from 2005 through 2012. Two different cut-off levels were used for negative NT-proBNP in the rule-out test: 300 and 400 pg/mL. The cost-effectiveness of the testing strategy was estimated through the short-term cost avoidance and reduction in demand for echocardiographies.RESULTS:The female patients were slightly older than the males. Based on the data from 2012, the estimated costs for NT-proBNP tests and echocardiographies per county were reduced by EUR 300000/100000 inhabitants with the 300 pg/mL cut-off and EUR 350000/100000 inhabitants with the 400 pg/mL.CONCLUSIONS:The use of NT-proBNP as a rule-out test in a sequential testing strategy reduced the cost for diagnostic work-up of primary care patients with suspected heart failure.
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| 21. |
- Larsson, Anders, et al.
(author)
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Pentraxin 3 Values During Normal Pregnancy
- 2011
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In: Inflammation. - : Springer Science and Business Media LLC. - 0360-3997 .- 1573-2576. ; 34:5, s. 448-451
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Journal article (peer-reviewed)abstract
- Pentraxin 3 (PTX3) is an inflammatory molecule that has been reported to be a promising early biomarker for subsequent preeclampsia. The levels of PTX3 vary during pregnancy and it is thus a need to establish reference intervals during normal pregnancy. Repeated blood samples were collected from 52 healthy pregnant females. The samples were divided according to collection time into the following groups: week 7-17, week 17-24, week 24-28, week 28-31, week 31-34, week 34-38, before delivery and after delivery. The samples were analyzed for PTX3 with a sandwich ELISA and the 2.5 and 97.5 percentiles for each sample period was calculated. There was a continuous increase of serum PTX3 as pregnancy progressed. The increase was most evident after week 31 with the highest levels just before delivery.
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| 22. |
- Miles, Elizabeth A, et al.
(author)
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The Salmon in Pregnancy Study : study design, subject characteristics, maternal fish and marine n-3 fatty acid intake, and marine n-3 fatty acid status in maternal and umbilical cord blood
- 2011
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In: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 94:6, s. 1986S-1992S
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Journal article (peer-reviewed)abstract
- BACKGROUND: Oily fish provides marine n-3 (omega-3) fatty acids that are considered to be important in the growth, development, and health of the fetus and newborn infant. OBJECTIVES: The objectives were to increase salmon consumption among pregnant women and to determine the effect on maternal and umbilical cord plasma marine n-3 fatty acid content. DESIGN: Women (n = 123) with low habitual consumption of oily fish were randomly assigned to continue their habitual diet or were provided with 2 portions of farmed salmon/wk to include in their diet from week 20 of pregnancy until delivery. RESULTS: Median weekly consumption frequency of study salmon in the salmon group was 1.94 portions, and total fish consumption frequency was 2.11 portions/wk in the salmon group and 0.47 portions/wk in the control group (P < 0.001). Intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from the diet, from seafood, and from oily fish were higher in the salmon group (all P < 0.001). Percentages of EPA and DHA in plasma phosphatidylcholine decreased during pregnancy in the control group (P for trend = 0.029 and 0.008, respectively), whereas they increased in the salmon group (P for trend for both < 0.001). EPA and DHA percentages were higher in maternal plasma phosphatidylcholine at weeks 34 and 38 of pregnancy and in umbilical cord plasma phosphatidylcholine in the salmon group (P < 0.001 for all). CONCLUSION: If pregnant women, who do not regularly eat oily fish, eat 2 portions of salmon/wk, they will increase their intake of EPA and DHA, achieving the recommended minimum intake; and they will increase their and their fetus' status of EPA and DHA. This trial was registered at clinicaltrials.gov as NCT00801502.
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| 23. |
- Nerpin, Elisabet, et al.
(author)
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Association between glomerular filtration rate and endothelial function in an elderly community cohort
- 2012
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In: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 224:1, s. 242-246
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Journal article (peer-reviewed)abstract
- BACKGROUND: Endothelial dysfunction is prevalent among individuals with chronic kidney disease. However, the association between glomerular filtration rate and endothelial function in the community is unclear and needs to be investigated in the general population.METHODS: In the community-based Prospective Investigation of the Vasculature of Uppsala Seniors study (PIVUS, n = 952, mean age 70, women 49.3%), we investigated cross-sectional associations between estimated cystatin C-based glomerular filtration rate (eGFR), and 3 measures representing different aspects of endothelial function (endothelial-dependent vasodilation [EDV], endothelial independent vasodilatation [EIDV], and flow-mediated dilatation [FMD]). We also performed pre-specified sub-group analyses in participants with normal eGFR (>60 ml/min/1.73 m(2)).RESULTS: In the whole cohort, 10 ml/min/1.73 m(2) higher eGFR was associated with 3% higher EDV (p = 0.001) and 2% higher EIDV (p = 0.007), adjusted for age and sex. The associations were attenuated and no longer statistically significant after adjusting for established cardiovascular risk factors. In participants with eGFR >60 ml/min/1.73 m(2), 10 ml higher eGFR was associated with 2% higher EDV (p = 0.04) after adjusting for sex and age. eGFR was not associated to FMD in any model or sub-sample.CONCLUSION: This community-based study suggests that eGFR is associated with endothelial function also in persons with normal kidney function, but that this association is largely explained by confounding by established cardiovascular risk factors. Thus, our data do not support the notion of a direct causal interplay between renal and vascular function prior to the development of CKD.
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| 24. |
- Nerpin, Elisabet, et al.
(author)
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Inflammation, oxidative stress, glomerular filtration rate, and albuminuria in elderly men : a cross-sectional study
- 2012
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In: BMC research notes. - : BioMed Central. - 1756-0500. ; 5:1, s. 537-
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Journal article (peer-reviewed)abstract
- BACKGROUND: The role of inflammation and oxidative stress in mild renal impairment in the elderly is not well studied. Accordingly, we aimed at investigating the associations between estimated glomerular filtration rate (eGFR), albumin/creatinine ratio (ACR), and markers of different inflammatory pathways and oxidative stress in a community based cohort of elderly men. FINDINGS: Cystatin C-based GFR, ACR, and biomarkers of cytokine-mediated inflammation (interleukin-6, high-sensitivity C-reactive protein[CRP], serum amyloid A[SAA]), cyclooxygenase-mediated inflammation (urinary prostaglandin F2alpha [PGF2alpha]), and oxidative stress (urinary F2 isoprostanes) were assessed in the Uppsala Longitudinal Study of Adult Men(n = 647, mean age 77 years). RESULTS: In linear regression models adjusting for age, BMI, smoking, blood pressure, LDL-cholesterol, HDL-cholesterol, triglycerides, and treatment with statins, ACE-inhibitors, ASA, and anti-inflammatory agents, eGFR was inversely associated with CRP, interleukin-6, and SAA (beta-coefficient -0.13 to -0.19, p < 0.001 for all), and positively associated with urinary F2-isoprostanes (beta-coefficient 0.09, p = 0.02). In line with this, ACR was positively associated with CRP, interleukin-6, and SAA (beta- coefficient 0.09-0.12, p < 0.02 for all), and negatively associated with urinary F2-isoprostanes (beta-coefficient -0.12, p = 0.002). The associations were similar but with lower regression coefficients in a sub-sample with normal eGFR (>60 ml/min/1.73 m2, n = 514), with the exception that F2-isoprostane and SAA were no longer associated with eGFR. CONCLUSION: Our data indicate that cytokine-mediated inflammation is involved in the early stages of impaired kidney function in the elderly, but that cyclooxygenase-mediated inflammation does not play a role at this stage. The unexpected association between higher eGFR/lower albuminuria and increased F2-isoprostanes in urine merits further studies.
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| 25. |
- Ridefelt, Peter, et al.
(author)
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Increased plasma glucose levels after change of recommendation from NaF to citrate blood collection tubes
- 2014
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In: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 47:7-8, s. 625-628
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Journal article (peer-reviewed)abstract
- Objectives: To evaluate changes in plasma glucose measurements in an unselected patient population after a change of recommendation from NaF to citrate blood collection vacuum tubes. Design and methods: Glucose (n = 460 751) and HbA1c (n = 55 190) determinations during a period of approximately three years before and after the tube change were extracted from a laboratory information system. Results: Median values for plasma glucose determinations increased from 6.03 before to 6.28 mmol/L after the tube change. The proportion of glucose determinations above the WHO limit for impaired fasting glucose (6.1 mmol/L) and the medical decision limit for diabetes (7.0 mmol/L) increased from 48.1 to 55.4% after the change. Conclusions: The change from NaF to citrate tubes caused higher glucose values, and consequently more glucose determinations above the decision limit for diabetes.
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