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Nerpin, E., Olivieri, M., Gislason, T., Olin, A. C., Nielsen, R., Johannessen, A., . . . Malinovschi, A. (2019). Determinants of fractional exhaled nitric oxide in healthy men and women from the European Community Respiratory Health Survey III. Clinical and Experimental Allergy, 49(7), 969-979
Open this publication in new window or tab >>Determinants of fractional exhaled nitric oxide in healthy men and women from the European Community Respiratory Health Survey III
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2019 (English)In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 49, no 7, p. 969-979Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: The fractional exhaled nitric oxide (FE NO) is a marker for type 2 inflammation used in diagnostics and management of asthma. In order to use FE NO as a reliable biomarker, it is important to investigate factors that influence FE NO in healthy individuals. Men have higher levels of FE NO than women, but it is unclear whether determinants of FE NO differ by sex.

OBJECTIVE: To identify determinants of FE NO in men and women without lung diseases.

METHOD: FE NO was validly measured in 3,881 healthy subjects that had answered the main questionnaire of the European Community Respiratory Health Survey III without airways or lung disease RESULTS: Exhaled NO levels were 21.3% higher in men compared with women p<0.001. Being in the upper age quartile (60.3-67.6 years) men had 19.2 ppb (95% CI: 18.3, 20.2) higher FE NO than subjects in the lowest age quartile (39.7-48.3 years) p=0.02. Women in the two highest age quartiles (54.6-60.2 and 60.3-67.6 years) had 15.4 ppb (14.7, 16.2), p=0.03 and 16.4 ppb (15.6, 17.1), p=<0.001 higher FE NO, compared with the lowest age quartile. Height was related to 8% higher FE NO level in men (p<0.001) and 5% higher FE NO levels in women (p=0.008). Men who smoked had 37% lower FE NO levels and women had 30% lower levels compared with never-smokers (p<0.001 for both). Men and women sensitized to both grass and perennial allergens had higher FE NO levels compared with non-sensitized subjects 26% and 29%, p<0.001 for both.

CONCLUSION & CLINICAL RELEVANCE: FE NO levels were higher in men than women. Similar effects of current smoking, height, and IgE sensitization were found in both sexes. FE NO started increasing at lower age in women than in men, suggesting that interpretation of FE NO levels in adults aged over 50 years should take into account age and sex. 

Keywords
FENO, IgE sensitization, healthy population, smoking
National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-29858 (URN)10.1111/cea.13394 (DOI)000474610200004 ()30934155 (PubMedID)2-s2.0-85064513946 (Scopus ID)
Available from: 2019-04-05 Created: 2019-04-05 Last updated: 2019-07-29Bibliographically approved
Nerpin, E., Joao, F. A., Alving, K., Jansson, C. & Malinovschi, A. (2018). Blood cell counts and C-reactive protein inrelation to lung function in NHANES 2007-2010. In: : . Paper presented at ERS 2018 Paris International Congress, Madrid 28 Sept - 2 October.
Open this publication in new window or tab >>Blood cell counts and C-reactive protein inrelation to lung function in NHANES 2007-2010
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2018 (English)Conference paper, Oral presentation with published abstract (Other academic)
Abstract [en]

Background:

Low-grade systemic inflammation is associated with impaired lung function. Few studies have examined if C-reactive protein (CRP), blood eosinophil (B-Eos), and blood neutrophil (B-Neu) counts offer additive information in relation to lung function. The aim of this study was to analyse associations between CRP, BEos, and B-Neu and effects on lung function, with special regards to additive information.

Methods:

Cross-sectional study on 7,753 participants, 20-80 years of age, in the National Health and Nutrition Examination Survey. Gender-based tertiles for CRP, B-Eos, and B-Neu were analyzed in relation to forced expiratory volume in 1 second (FEV1 % predicted), forced vital capacity (FVC % predicted), and FEV1/FVC ratio.

Results:

CRP, B-Eos, and B-Neu were inversely related to FEV1 and FVC. Only B-Eos and B-Neu were inversely related to FEV1/FVC ratio. Further, lower lung function was found with increased number of elevated

inflammatory markers in the highest tertile (one, two or three vs. non elevated) for FEV1 (% predicted): β-coefficients (95% CI) -2.20(-2.98, -1.41), -4.43 (-5.39, -3.45), and -6.43(-8.07, -4.79), all P=0.001; FVC (% predicted): -1.70 (-2.42, -0.98), -3.17 (-4.06, -2.29), and -5.34 (-6.85, -3.84), all P=0.001.

Conclusion:

CRP, B-Eos, and B-Neu offer independent and additive information in relation to lower FEV1 and FVC in the general population. This indicates that a combination of biomarkers yields more information than the biomarkers assessed individually. The mechanisms appear to be different, as B-Neu and B-Eos seem to relate more closely to obstructive impairment, e.g., lower FEV1/FVC ratio, which was not found for CRP.

Keywords
Inflammation, Epidemiology, Spirometry
National Category
Basic Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-28923 (URN)
Conference
ERS 2018 Paris International Congress, Madrid 28 Sept - 2 October
Available from: 2018-11-25 Created: 2018-11-25 Last updated: 2018-11-26Bibliographically approved
Nerpin, E., Jarvis, D., Olivieri, M., Gislason, T., Olin, A., Jansson, C. & Malinovschi, A. (2018). Different relation between exhaled nitric oxide and lung function with regard to current smoking. In: : . Paper presented at ERS 2018 Paris International Congress, Madrid 28 Sept - 2 Oct..
Open this publication in new window or tab >>Different relation between exhaled nitric oxide and lung function with regard to current smoking
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2018 (English)Conference paper, Oral presentation with published abstract (Other academic)
Abstract [en]

Background: Exhaled nitric oxide (FeNO) is a non-invasive marker of airway inflammation. Smokingreduces FeNO by 30-60%. Weak positive relation between lung function and FeNO has been inconsistently described. This has not been separately for smokers. Therefore we investigated the relation between lung function and FeNO with regard to smoking.

Methods: FeNO and lung function post-bronchodilation (BD) were measured in 4813 subjects from the European Community Respiratory Health Survey III. GLI reference values were used. Smoking habits were self-reported.

Results: Current smokers with FEV1 <lower limit of normal (LLN) had lower FeNO levels (ppb, geometric mean (95%CI)) than subjects with FEV1 ≥LLN: 10.1 (9.1, 11.1) vs 11.7 (11.3, 12.2), p=0.005, while the opposite was found in non-smokers: 20.0 (18.4, 21.6) vs 18.5 (18.2, 18.8), p=0.03. This interaction with current smoking was significant both before and after adjustments for study centres, age, BMI and gender (p=0.001 and p=0.004). Current smokers with FEV1/FVC <LLN had lower FeNO than current smokers with FEV1/FVC ≥LLN: 10.5 (9.4, 11.6) vs 11.6 (11.2, 12.1), p=0.04, and the opposite was found in non-smokers: 20.8 (19.1, 22.7) vs 18.4 (18.1, 18.8), p<0.001. There was a significant interaction with current smoking both in unadjusted and adjusted models (both p<0.001).

Conclusion: Higher FeNO relates with lower FEV1 and FEV1/FVC-ratio among non-smoking individuals, suggesting that the obstruction is related with airways inflammation. In current smokers, higher FeNO relates with better preserved lung function and this finding warrants further studies to understand the underlying mechanisms. Presented on behalf of ECRHS III (www.ecrhs.org)

National Category
Basic Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-28924 (URN)
Conference
ERS 2018 Paris International Congress, Madrid 28 Sept - 2 Oct.
Available from: 2018-11-25 Created: 2018-11-25 Last updated: 2018-11-26Bibliographically approved
Nerpin, E., Jacinto, T., Fonseca, J. A., Alving, K., Janson, C. & Malinovschi, A. (2018). Systemic inflammatory markers in relation to lung function in NHANES. 2007–2010. Respiratory Medicine, 142, 94-100
Open this publication in new window or tab >>Systemic inflammatory markers in relation to lung function in NHANES. 2007–2010
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2018 (English)In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 142, p. 94-100Article in journal (Refereed) Published
Abstract [en]

Background Low-grade systemic inflammation, mainly assessed by C-reactive protein (CRP), has been associated with impaired lung function. Few studies have studied if CRP, blood eosinophils, and blood neutrophils offer additive information in relation to lung function. Objectives To analyse associations between lung function and CRP, blood eosinophils, and blood neutrophils, with special regard to additive information of combining the inflammatory markers. Methods Cross-sectional study on 7753 participants, 20–80 years of age, in the National Health and Nutrition Examination Survey. Gender-based tertiles for CRP, blood eosinophils, and blood neutrophils were analysed in relation to the following lung function parameters: forced expiratory volume in 1 s (FEV1% predicted), forced vital capacity (FVC % predicted), and FEV1/FVC ratio. Results CRP, blood eosinophils, and blood neutrophils levels were inversely related to FEV1 and FVC. Only blood eosinophils and blood neutrophils were inversely related to FEV1/FVC ratio. Further, lower lung function was found with increased number of elevated inflammatory markers in the highest tertile (one, two or three vs. non elevated) for FEV1 (β-coeff., −2.20, −4.43, and −6.43, p < 0.001) and FVC (β-coeff., −1.70, −3.15 and −5.33, p < 0.001), respectively. Conclusions & clinical relevance CRP, blood eosinophils, and blood neutrophils offer independent and additive information in relation to lower FEV1 and FVC in the general population. This indicates that a combination of biomarkers yields more information than the biomarkers assessed individually.

Keywords
Inflammation, CRP, Blood eosinophils, Blood neutrophils
National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-28458 (URN)10.1016/j.rmed.2018.07.011 (DOI)000443001500015 ()30170809 (PubMedID)2-s2.0-85051648358 (Scopus ID)
Available from: 2018-09-03 Created: 2018-09-03 Last updated: 2018-09-13Bibliographically approved
Brück, K., Jager, K. J., Dounousi, E., Kainz, A., Nitsch, D., Ärnlöv, J., . . . Ferraro, P. M. (2015). Methodology used in studies reporting chronic kidney disease prevalence: a systematic literature review. Nephrology, Dialysis and Transplantation, 30(Supp. 4), iv6-iv16
Open this publication in new window or tab >>Methodology used in studies reporting chronic kidney disease prevalence: a systematic literature review
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2015 (English)In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 30, no Supp. 4, p. iv6-iv16Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Many publications report the prevalence of chronic kidney disease (CKD) in the general population. Comparisons across studies are hampered as CKD prevalence estimations are influenced by study population characteristics and laboratory methods.

METHODS: For this systematic review, two researchers independently searched PubMed, MEDLINE and EMBASE to identify all original research articles that were published between 1 January 2003 and 1 November 2014 reporting the prevalence of CKD in the European adult general population. Data on study methodology and reporting of CKD prevalence results were independently extracted by two researchers.

RESULTS: We identified 82 eligible publications and included 48 publications of individual studies for the data extraction. There was considerable variation in population sample selection. The majority of studies did not report the sampling frame used, and the response ranged from 10 to 87%. With regard to the assessment of kidney function, 67% used a Jaffe assay, whereas 13% used the enzymatic assay for creatinine determination. Isotope dilution mass spectrometry calibration was used in 29%. The CKD-EPI (52%) and MDRD (75%) equations were most often used to estimate glomerular filtration rate (GFR). CKD was defined as estimated GFR (eGFR) <60 mL/min/1.73 m(2) in 92% of studies. Urinary markers of CKD were assessed in 60% of the studies. CKD prevalence was reported by sex and age strata in 54 and 50% of the studies, respectively. In publications with a primary objective of reporting CKD prevalence, 39% reported a 95% confidence interval.

CONCLUSIONS: The findings from this systematic review showed considerable variation in methods for sampling the general population and assessment of kidney function across studies reporting CKD prevalence. These results are utilized to provide recommendations to help optimize both the design and the reporting of future CKD prevalence studies, which will enhance comparability of study results.

National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-18989 (URN)10.1093/ndt/gfv131 (DOI)26209739 (PubMedID)
Available from: 2015-08-12 Created: 2015-08-12 Last updated: 2017-12-04Bibliographically approved
Jobs, E., Adamsson, V., Larsson, A., Jobs, M., Nerpin, E., Ingelsson, E., . . . Risérus, U. (2014). Influence of a prudent diet on circulating cathepsin S in humans. Nutrition Journal, 13(84)
Open this publication in new window or tab >>Influence of a prudent diet on circulating cathepsin S in humans
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2014 (English)In: Nutrition Journal, ISSN 1475-2891, E-ISSN 1475-2891, Vol. 13, no 84Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Increased circulating cathepsin S levels have been linked to increased risk of cardiometabolic diseases and cancer. However, whether cathepsin S is a modifiable risk factor is unclear. We aimed to investigate the effects of a prudent diet on plasma cathepsin S levels in healthy individuals.

FINDINGS: Explorative analyses of a randomized study were performed in 88 normal to slightly overweight and hyperlipidemic men and women (aged 25 to 65) that were randomly assigned to ad libitum prudent diet, i.e. healthy Nordic diet (ND) or a control group (habitual Western diet) for 6 weeks. Whereas all foods in the ND were provided, the control group was advised to consume their habitual diet throughout the study. The ND was in line with dietary recommendations, e.g. low in saturated fats, sugars and salt, but high in plant-based foods rich in fibre and unsaturated fats.The ND significantly decreased cathepsin S levels (from 20.1 (+/-4.0 SD) to 19.7 μg/L (+/-4.3 SD)) compared with control group (from 18.2 (+/-2.9 SD) to 19.1 μg/L (+/-3.8 SD)). This difference remained after adjusting for sex and change in insulin sensitivity (P = 0.03), and near significant after adjusting for baseline cathepsin S levels (P = 0.06), but not for change in weight or LDL-C. Changes in cathepsin S levels were directly correlated with change in LDL-C.

CONCLUSIONS: Compared with a habitual control diet, a provided ad libitum healthy Nordic diet decreased cathepsin S levels in healthy individuals, possibly mediated by weight loss or lowered LDL-C. These differences between groups in cathepsin S were however not robust and therefore need further investigation.

Place, publisher, year, edition, pages
BioMed Central, 2014
Keywords
Nordic prudent diet; Cathepsin S; Weight loss; Cardiometabolic risk factors
National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-15286 (URN)10.1186/1475-2891-13-84 (DOI)000341112000001 ()25128296 (PubMedID)
Available from: 2014-09-09 Created: 2014-09-09 Last updated: 2017-12-05Bibliographically approved
Nerpin, E., Ingelsson, E., Riserus, U., Sundström, J., Andren, B., Jobs, E., . . . Ärnlöv, J. (2014). The association between glomerular filtration rate and left ventricular function in two independent community-based cohorts of elderly. Nephrology, Dialysis and Transplantation, 29(11), 2069-2074
Open this publication in new window or tab >>The association between glomerular filtration rate and left ventricular function in two independent community-based cohorts of elderly
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2014 (English)In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 29, no 11, p. 2069-2074Article in journal (Refereed) Published
Abstract [en]

The cardiorenal syndrome, the detrimental bi-directional interplay between symptomatic heart failure and chronic kidney disease, is a major clinical challenge. Nonetheless, it is unknown if this interplay begins already at an asymptomatic stage. Therefore we investigated whether the glomerular filtration rate (GFR) is associated with left ventricular function in participants free from clinical heart failure and with a left ventricular ejection fraction (LVEF) > 40% and with pre-specified sub-group analyses in individuals with a GFR > 60 mL/min/m(2). Two independent community-based cohorts were used; the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 911; 50% women; mean age: 70 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 538; mean age: 71 years). We investigated cross-sectional association between cystatin C-based GFR (estimated glomerular function [eGFR]) and systolic (LVEF), diastolic- (isovolumic relaxation time [IVRT]) and global left ventricular function (myocardial performance index [MPI]) determined by echocardiography. In both PIVUS and ULSAM, higher eGFR was significantly associated with higher LVEF (P = 0.004 [PIVUS] and P = 0.005 [ULSAM]). In PIVUS, higher eGFR was significantly associated with lower IVRT (P = 0.001) and MPI (P = 0.006), in age- and sex-adjusted models. After further adjustment for cardiovascular risk factors, the association between higher eGFR and higher LVEF was still statistically significant (P = 0.008 [PIVUS] and P = 0.02 [ULSAM]). In PIVUS, the age- and sex-adjusted association between eGFR and left ventricular function was similar in participants with eGFR > 60 mL/min/m(2). Our data suggest that the interplay between kidney and heart function begins prior to the development of symptomatic heart failure and kidney disease.

National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-13504 (URN)10.1093/ndt/gfu199 (DOI)000344625400015 ()24916339 (PubMedID)
Available from: 2013-12-12 Created: 2013-12-12 Last updated: 2017-12-06Bibliographically approved
Nerpin, E. (2013). The kidney in different stages of the cardiovascular continuum. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
Open this publication in new window or tab >>The kidney in different stages of the cardiovascular continuum
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Patients with chronic kidney disease are at higher risk of developing cardiovascular disease. The complex, interaction between the kidney and the cardiovascular system is incompletely understood, particularly at the early stages of the cardiovascular continuum.

The overall aim of this thesis was to clarify novel aspects of the interplay between the kidney and the cardiovascular system at different stages of the cardiovascular continuum; from risk factors such as insulin resistance, inflammation and oxidative stress, via sub-clinical cardiovascular damage such as endothelial dysfunction and left ventricular dysfunction, to overt cardiovascular death.

This thesis is based on two community-based cohorts of elderly, Uppsala Longitudinal Study of Adult Men (ULSAM) and Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS).

The first study, show that higher insulin sensitivity, measured with euglycemic-hyperinsulinemic clamp technique was associated to improve estimated glomerular filtration rate (eGFR) in participants with normal fasting plasma glucose, normal glucose tolerance and normal eGFR. In longitudinal analyses, higher insulin sensitivity at baseline was associated with lower risk of impaired renal function during follow-up. In the second study, eGFR was inversely associated with different inflammatory markers (C-reactive protein, interleukin-6, serum amyloid A) and positively associated with a marker of oxidative stress (urinary F2-isoprostanes). In line with this, the urinary albumin/creatinine ratio was positively associated with these inflammatory markers, and negatively associated with oxidative stress.

In study three, higher eGFR was associated with better endothelial function as assessed by the invasive forearm model. Further, in study four, higher eGFR was significantly associated with higher left ventricular systolic function (ejection fraction). The 5th study of the thesis shows that higher urinary albumin excretion rate (UAER) and lower eGFR was independently associated with an increased risk for cardiovascular mortality. Analyses of global model fit, discrimination, calibration, and reclassification suggest that UAER and eGFR add relevant prognostic information beyond established cardiovascular risk factors in participants without prevalent cardiovascular disease.

Conclusion: this thesis show that the interaction between the kidney and the cardiovascular system plays an important role in the development of cardiovascular disease and that this interplay begins at an early asymptomatic stage of the disease process.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. p. 72
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206; 946 ; 946
Keywords
epidemiology, chronic kidney disease, cystatin C, glomerular filtration rate, albuminuria, euglycemic hyperinsulinemic clamp, insulin sensitivity, inflammation, oxidative stress, endothelial dysfunction and left ventricular dysfunction
National Category
Cardiac and Cardiovascular Systems Urology and Nephrology Gerontology, specialising in Medical and Health Sciences
Research subject
Health and Welfare, Nedsatt njurfunktion, insulinresistens, oxidativ stress och utvecklingen av hjärt-kärlsjukdomar
Identifiers
urn:nbn:se:du-13489 (URN)978-91-554-8792-8 (ISBN)
Public defence
2013-12-05, Universitetshuset Sal IX, Uppsala, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2013-12-12 Created: 2013-12-10 Last updated: 2018-01-11Bibliographically approved
Nerpin, E., Ingelsson, E., Risérus, U., Helmersson-Karlqvist, J., Sundström, J., Jobs, E., . . . Ärnlöv, J. (2012). Association between glomerular filtration rate and endothelial function in an elderly community cohort. Atherosclerosis, 224(1), 242-246
Open this publication in new window or tab >>Association between glomerular filtration rate and endothelial function in an elderly community cohort
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2012 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 224, no 1, p. 242-246Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Elsevier, 2012
Keywords
Chronic kidney disease; Endothelium-dependent vasodilatation; Endothelial dysfunction; Flow-mediated dilatation; Glomerular filtration rate; Epidemiology
National Category
Cardiac and Cardiovascular Systems
Research subject
Hälsa och välfärd
Identifiers
urn:nbn:se:du-10574 (URN)10.1016/j.atherosclerosis.2012.07.008 (DOI)000308078000038 ()22841608 (PubMedID)
Available from: 2012-08-22 Created: 2012-08-22 Last updated: 2017-12-07Bibliographically approved
Nerpin, E., Helmersson-Karlqvist, J., Riserus, U., Sundström, J., Larsson, A., Jobs, E., . . . Ärnlöv, J. (2012). Inflammation, oxidative stress, glomerular filtration rate, and albuminuria in elderly men: a cross-sectional study. BMC research notes, 5(1), 537
Open this publication in new window or tab >>Inflammation, oxidative stress, glomerular filtration rate, and albuminuria in elderly men: a cross-sectional study
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2012 (English)In: BMC research notes, ISSN 1756-0500, Vol. 5, no 1, p. 537-Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
BioMed Central, 2012
Keywords
Inflammation; Oxidative stress; Glomerular filtration rate and albuminuria
National Category
Urology and Nephrology
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-11503 (URN)10.1186/1756-0500-5-537 (DOI)23016573 (PubMedID)
Note

Open access

Available from: 2012-12-19 Created: 2012-12-19 Last updated: 2016-05-31Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-3880-2132

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