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51.
  • Pottel, Hans, et al. (författare)
  • Development and Validation of a Modified Full Age Spectrum Creatinine-Based Equation to Estimate Glomerular Filtration Rate : A Cross-sectional Analysis of Pooled Data
  • 2021
  • Ingår i: Annals of Internal Medicine. - : American College of Physicians. - 0003-4819 .- 1539-3704. ; 174:2, s. 183-191
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The Chronic Kidney Disease in Children Study (CKiD) equation for children and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for adults are recommended serum creatinine (SCr)-based calculations for estimating glomerular filtration rate (GFR). However, these equations, as well as their combination, have limitations, notably the problem of implausible changes in GFR during the transition from adolescence to adulthood and overestimation of GFR in young adults. The full age spectrum (FAS) equation addresses these issues but overestimates GFR when SCr levels are low.OBJECTIVE: To develop and validate a modified FAS SCr-based equation combining design features of the FAS and CKD-EPI equations.DESIGN: Cross-sectional analysis with separate pooled data sets for development and validation.SETTING:  = 13) with measured GFR available.PATIENTS: 11 251 participants in 7 studies (development and internal validation data sets) and 8378 participants in 6 studies (external validation data set).MEASUREMENTS: Clearance of an exogenous marker (reference method), SCr level, age, sex, and height were used to develop a new equation to estimate GFR.RESULTS: ] in adults) across the FAS (2 to 90 years) and SCr range (40 to 490 µmol/L [0.45 to 5.54 mg/dL]) and with fewer estimation errors exceeding 30% (6.5% [CI, 3.8% to 9.1%] in children and 3.1% [CI, 2.5% to 3.6%] in adults) compared with the CKiD and CKD-EPI equations.LIMITATION: No Black patients were included.CONCLUSION: The new EKFC equation shows improved accuracy and precision compared with commonly used equations for estimating GFR from SCr levels.PRIMARY FUNDING SOURCE: Swedish Research Council (Vetenskapsrådet).
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52.
  • Pottel, Hans, et al. (författare)
  • Standardization of serum creatinine is essential for accurate use of unbiased estimated GFR equations : evidence from three cohorts matched on renal function
  • 2022
  • Ingår i: Clinical Kidney Journal. - : Oxford University Press. - 2048-8505 .- 2048-8513. ; 15:12, s. 2258-2265
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Differences in the performance of estimated glomerular filtration rate (eGFR) equations have been attributed to the mathematical form of the equations and to differences between patient demographics and measurement methods. We evaluated differences in serum creatinine (SCr) and eGFR in cohorts matched for age, sex, body mass index (BMI) and measured GFR (mGFR).Methods: White North Americans from Minnesota (n = 1093) and the Chronic Renal Insufficiency Cohort (CRIC) (n = 1548) and White subjects from the European Kidney Function Consortium (EKFC) cohort (n = 7727) were matched for demographic patient characteristics (sex, age +/- 3 years, BMI +/- 2.5 kg/m(2)) and renal function (mGFR +/- 3 ml/min/1.73 m(2)). SCr was measured with isotope dilution mass spectrometry (IDMS)-traceable assays in the Minnesota and EKFC cohorts and with non-standardized SCr assays recalculated to IDMS in the CRIC. The Minnesota cohort and CRIC shared a common method to measure GFR (renal clearance of iothalamate), while the EKFC cohort used a variety of exogenous markers and methods, all with recognized sufficient accuracy. We compared the SCr levels and eGFR predictions [for Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and EKFC equations] of patients fulfilling these matching criteria.Results: For 305 matched individuals, mean SCr (mg/dL) was not different between the Minnesota and EKFC cohorts (females 0.83 +/- 0.20 versus 0.86 +/- 0.23, males 1.06 +/- 0.23 versus 1.12 +/- 0.37; P > .05) but significantly different from the CRIC [females 1.13 +/- 0.23 (P < .0001), males 1.42 +/- 0.31 (P < .0001)]. The CKD-EPI equations performed better than the EKFC equation in the CRIC, while the opposite was true in the Minnesota and EKFC cohorts.Conclusion: Significant differences in SCr concentrations between the Minnesota and EKFC cohorts versus CRIC were observed in subjects with the same level of mGFR and equal demographic characteristics and can be explained by the difference in SCr calibration.Lay Summary: Standardization of serum creatinine (SCr) measurement is fundamental for estimating glomerular filtration rate (GFR). We used data with GFR measured by a reference method from three cohorts: Chronic Renal Insufficiency Cohort (CRIC, n = 1548), Minnesota cohort (n = 1093) and European Kidney Function Consortium cohort (EKFC; n = 7727). In the EKFC and Minnesota cohorts, SCr was measured by standardized methods, although SCr 'calibration' was more debatable in the CRIC. GFR was measured by the same method in the CRIC and Minnesota cohort. Then we matched 305 White subjects for sex, measured GFR (+/- 3 ml/min/1.73 m(2)), age (+/- 3 years) and body mass index (+/- 2.5 kg/m(2)). From these matched subjects we showed that the association between SCr and measured GFR was quite similar between subjects from the Minnesota and EKFC cohorts, but different between the CRIC and EKFC cohort and between the Minnesota cohort and CRIC. These differences lead to discrepancies in the analysis of the performance of different creatinine-based equations.
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53.
  • Svenungsson, Elisabet, et al. (författare)
  • Complement deposition, C4d, on platelets is associated with vascular events in systemic lupus erythematosus
  • 2020
  • Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 59:11, s. 3264-3274
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. Complement components, including C4d, can be found on activated platelets, a process associated with vascular disease in SLE. We investigated whether platelet C4d (PC4d) adds additional value to traditional and known lupus-associated risk factors when identifying SLE patients with vascular disease. Methods. This cross-sectional study included 308 well-characterized SLE patients and 308 matched general population controls. PC4d deposition was analysed using flow cytometry. Values >95% of controls were considered as PC4d positive (+). aPL were determined by Luminex, and the LA test was performed by DRVVT. History of vascular disease (composite and as separate outcomes) was defined at inclusion. Results. SLE patients had increased PC4d deposition as compared with population controls (50 vs 5%, P < 0.0001). PC4d+ positively associated with any vascular events, and separately with venous and cerebrovascular events, and also with all investigated aPL profiles. The association for any vascular event remained statistically significant after adjustment for traditional and SLE-associated risk factors (odds ratio: 2.3, 95% CI: 1.3, 4.3, P = 0.008). Compared with patients negative for both PC4d and LA, patients with double positivity were more likely to have vascular disease (odds ratio: 12.3, 95% CI: 5.4, 29.3; attributable proportion due to interaction 0.8, 95% CI: 0.4, 1.1) Conclusion. PC4d+ is associated with vascular events in SLE, independently of traditional and SLE-associated risk factors. Concurrent presence of PC4d and LA seem to interact to further increase the odds for vascular events. Prospective studies should examine whether the aPL/PC4d combination can improve prediction of vascular events in SLE and/or APS.
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54.
  • Wollmer, Martin, et al. (författare)
  • Plasma calprotectin in the emergency department : a potential clinical biomarker for patients with infectious diseases
  • 2021
  • Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Taylor & Francis. - 0036-5513 .- 1502-7686. ; 81:7, s. 593-597
  • Tidskriftsartikel (refereegranskat)abstract
    • Increased levels of plasma calprotectin are reported in patients with infectious diseases. However, the clinical usefulness of calprotectin as a biomarker to identify patients with infectious diseases in the emergency department (ED) setting has not been investigated. To study the ability of calprotectin to discriminate patients with acute infectious diseases and dyspnea from patients with other causes of acute dyspnea in the ED setting. Patients aged ≥18 years seeking ED during daytime on weekdays between March 2013 and July 2018, with acute dyspnea, were included. Participants (n = 1287) were triaged according to Medical Emergency Triage and Treatment System-Adult score (METTS-A) or Rapid Emergency Triage and Treatment System (RETTS), and blood samples were collected. The association between calprotectin and other markers of infectious diseases, i.e. biomarkers (CRP, leucocytes) and body temperature, was studied. The predictive value of calprotectin for the outcome of acute infection was evaluated with receiver operating characteristic (ROC) analysis. Univariate cross-sectional regression showed significant associations between calprotectin and leucocytes, CRP and body temperature. Patients with severe infections including pneumonia (n = 119) had significantly higher concentrations of calprotectin compared to patients with heart failure (n = 162) or chronic obstructive pulmonary disease (n = 183). When tested for the outcome of acute infection (n = 109), the area under the ROC curve (AUROC) was for CRP 0.83 and for calprotectin 0.78. Plasma calprotectin identifies infectious diseases in ED patients with acute dyspnea, and the clinical usefulness of Calprotectin in the ED has to be further studied.
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55.
  • Wändell, Per, et al. (författare)
  • The association between BMI and 90-day mortality in patients with and without diabetes seeking care at the emergency department.
  • 2021
  • Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 126
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The impact of body mass index (BMI) on mortality varies with age and disease states. The aim of this research study was to analyse the associations between BMI categories and short- and long-term mortality in patients with or without diabetes seeking care at the emergency department (ED) with acute dyspnoea.Population and methods: Patients aged ≥18 years at ED during daytime on weekdays from March 2013 to July 2018 were included. Participants were triaged according to the Medical Emergency Triage and Treatment System-Adult score (METTS-A), and blood samples were collected. Totally, 1,710 patients were enrolled, with missing values in 113, leaving 1,597 patients, 291 with diabetes and 1,306 without diabetes. The association between BMI and short-term (90-day) and long-term (mean follow-up time 2.1 years) mortality was estimated by Cox regression with normal BMI (18.5-24.9) as referent category, with adjustment for age, sex, METTS-A scoring, glomerular filtration rate, smoking habits and cardiovascular comorbidity in a fully adjusted model. The Bonferroni correction was also used.Results: Regarding long-term mortality, patients with diabetes and BMI category ≥30 kg/m2 had a fully adjusted Hazard Ratio (HR) of 0.40 (95% confidence interval [CI]: 0.23-0.69), significant after the Bonferroni correction. Amongst patients without diabetes, those with underweight had an increased risk but only of borderline significance, whilst risks in those with overweight or obesity did not differ from reference.Regarding short-term mortality, risks did not differ from reference amongst patients with or without diabetes.Conclusions: We found divergent long-term mortality risks in patients with and without diabetes, with lower risk in obese patients (BMI ≥ 30 kg/m2) with diabetes, but no increased risk for patients without diabetes and overweight (BMI: 25-29.9 kg/m2) and obesity.
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56.
  • Wändell, Per, et al. (författare)
  • The C-reactive protein Albumin ratio was not consistently associated with cardiovascular and all-cause mortality in two community-based cohorts of 70-year-olds.
  • 2023
  • Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - 0036-5513 .- 1502-7686. ; , s. 1-5
  • Tidskriftsartikel (refereegranskat)abstract
    • C-reactive protein (CRP)/Albumin ratio (CAR) seems to mirror disease severity and prognosis in several acute disorders particularly in elderly patients, which we aimed to study. As method we use a prospective study design; the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 912, women 50%; mean age 70 years, baseline 2001 and 2004, median follow-up 15.0 years, end of follow-up 2019) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 924 mean age 71 years, baseline 1991-1995, median follow-up 15.6 years, end of follow-up 2016). Serum samples were used for analyses of CRP and Albumin. Cox regression analyses were performed for cardiovascular and all-cause mortality in models adjusting for several factors (age; physical activity; Interleukin-6; cardiovascular (CVD) risk factors: smoking, BMI level, systolic blood pressure, LDL-cholesterol, and diabetes), with 95% confidence interval (CI). When adjusting for age and CVD risk factors, CAR was significantly associated with cardiovascular mortality for meta-analyzed results from PIVUS and ULSAM, HR 1.09 (95% 1.01-1.18), but neither in PIVUS (HR 1.14, 95% CI 0.99-1.31) nor in ULSAM (1.07, 95% CI 0.98-1.17). Additionally, CAR was significantly associated with all-cause mortality in ULSAM 1.31 (95% CI 1.12-1.54) but not in PIVUS HRs 1.01 (95% 0.089-1.15). The predictive value of CAR was similar to CRP alone in PIVUS and ULSAM and slightly better than albumin for the prediction of CVD-mortality in ULSAM. In conclusion, CAR was not consistently associated with cardiovascular and all-cause mortality in the two cohorts. The prognostic value of CAR for long-term CVD-mortality was similar to CRP.
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57.
  • Wändell, P., et al. (författare)
  • TNFR1 is associated with short-term mortality in patients with diabetes and acute dyspnea seeking care at the emergency department
  • 2020
  • Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 57:10, s. 1145-1150
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Circulating levels of TNF alpha receptor 1 (TNFR1) and 2 (TNFR2) are associated with increased long-term mortality and impaired kidney function.AIM: To study association between circulating levels of TNFR1 and TNFR2 and short-term mortality in patients with diabetes and dyspnea.POPULATION AND METHODS: Patients aged ≥ 18 years seeking at emergency department (ED) during daytime on weekdays between December 2013 and July 2018, with diabetes and acute dyspnea, identified at the triage process, were included. Participants (n = 291) were triaged according to Medical Emergency Triage and Treatment System-Adult score, and blood samples were collected. Association between TNFR1 and TNFR2, respectively, and 90-day mortality were estimated by Cox regression models adjusted for age, sex, BMI, creatinine and CRP.RESULTS: Univariate models showed significant associations between TNFR1 and TNFR2, respectively, and CRP, age and creatinine. TNFR1 and TNFR2 tended to be elevated in patients with the highest triage level, compared to patients with lower triage levels (ns). In longitudinal analyses, TNFR1 but not TNFR2 was associated with increased short-term mortality, HR adjusted for age, BMI and creatinine 1.43 (95% CI 1.07-1.91), but not in the model also adjusted for CRP, HR 1.29 (95% CI 0.94-1.77). In secondary analysis for quartile 4 versus quartiles 1-3 of TNFR1, corresponding HRs were 2.46 (95% CI 1.27-5.15) and 2.21 (95% CI 1.07-2.56).CONCLUSIONS: We found a trend for the association between circulating TNFR1 levels and short-term mortality in patients with diabetes and acute dyspnea at the ED, possibly suggesting an inflammatory pathway for the association.
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60.
  • Helmersson, Johanna, et al. (författare)
  • Cystatin C predicts long term mortality better than creatinine in a nationwide study of intensive care patients
  • 2021
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 5882-
  • Tidskriftsartikel (refereegranskat)abstract
    • Decreased glomerular filtration rate (GFR) is linked to poor survival. The predictive value of creatinine estimated GFR (eGFR) and cystatin C eGFR in critically ill patients may differ substantially, but has been less studied. This study compares long-term mortality risk prediction by eGFR using a creatinine equation (CKD-EPI), a cystatin C equation (CAPA) and a combined creatinine/cystatin C equation (CKD-EPI), in 22,488 patients treated in intensive care at three University Hospitals in Sweden, between 2004 and 2015. Patients were analysed for both creatinine and cystatin C on the same blood sample tube at admission, using accredited laboratory methods. During follow-up (median 5.1 years) 8401 (37%) patients died. Reduced eGFR was significantly associated with death by all eGFR-equations in Cox regression models. However, patients reclassified to a lower GFR-category by using the cystatin C-based equation, as compared to the creatinine-based equation, had significantly higher mortality risk compared to the referent patients not reclassified. The cystatin C equation increased C-statistics for death prediction (p < 0.001 vs. creatinine, p = 0.013 vs. combined equation). In conclusion, this data favours the sole cystatin C equation rather than the creatinine or combined equations when estimating GFR for risk prediction purposes in critically ill patients.
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