| 1. |
- Andersson, Axel G, et al.
(författare)
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Large difference but high correlation between creatinine and cystatin C estimated glomerular filtration rate in Mesoamerican sugarcane cutters.
- 2022
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Ingår i: Occupational and environmental medicine. - : BMJ. - 1470-7926 .- 1351-0711. ; 79:7, s. 497-502
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Tidskriftsartikel (refereegranskat)abstract
- To explore the relationship between creatinine and cystatin C based estimated glomerular filtration rate (eGFR) in actively working sugarcane cutters.This cohort study included 458 sugarcane cutters from Nicaragua and El Salvador. Serum samples were taken before and at end of harvest seasons and analysed for creatinine and cystatin C. Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas were used to calculate eGFRs based on creatinine (eGFRcr), cystatin C (eGFRcys) and both creatinine and cystatin C (eGFRcrcys) at each time point. Bland-Altman plots and paired t-tests were used to compare the difference between eGFRcr and eGFRcys, and the difference in eGFRs between before and at end of the harvest seasons.The mean eGFRcr was higher than eGFRcys in both cohorts; absolute difference 22mL/min/1.73 m2 (95%CI 21 to 23) in Nicaragua and 13mL/min/1.73 m2 (95%CI 11 to 15) in El Salvador. Correlations between eGFRcr and eGFRcys were high, with r=0.69, 0.77 and 0.67 in Nicaragua at pre-harvest, end-harvest and cross-harvest, and r=0.89, 0.89 and 0.49 in El Salvador.Creatinine increases among heat-stressed workers reflect reduced glomerular filtration as estimated using eGFRcys, a marker independent of muscle mass and metabolism. The discrepancy between eGFRcr and eGFRcys may indicate reduced glomerular filtration of larger molecules and/or systemic bias in CKD-EPI performance in this population.
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| 2. |
- Björk, Jonas, et al.
(författare)
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Accuracy of GFR estimating equations combining standardized cystatin C and creatinine assays: a cross-sectional study in Sweden
- 2015
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 53:3, s. 403-414
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Tidskriftsartikel (refereegranskat)abstract
- Background: The recently established international cystatin C calibrator makes it possible to develop non-laboratory specific glomerular filtration rate (GFR) estimating (eGFR) equations. This study compares the performance of the arithmetic mean of the revised Lund-Malmo creatinine and CAPA cystatin C equations (MEAN(LM-REV+CAPA)), the arithmetic mean of the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) creatinine and cystatin C equations (MEAN(CKD-EPI)), and the composite CKD-EPI equation (CKD-EPICREA+CYSC) with the corresponding single marker equations using internationally standardized calibrators for both cystatin C and creatinine. Methods: The study included 1200 examinations in 1112 adult Swedish patients referred for measurement of GFR (mGFR) 2008-2010 by plasma clearance of iohexol (median 51 mL/min/1.73 m(2)). Bias, precision (interquartile range, IQR) and accuracy (percentage of estimates +/- 30% of mGFR; P-30) were compared. Results: Combined marker equations were unbiased and had higher precision and accuracy than single marker equations. Overall results of MEAN(LM-REV+CAPA)/MEAN(CKD-EPI)/CKD-EPICREA+CYSC were: median bias -2.2%/-0.5%/-1.6%, IQR 9.2/9.2/8.8 mL/min/1.73 m(2), and P-30 91.3%/91.0%/91.1%. The P-30 figures were about 7-14 -percentage points higher than the single marker equations. The combined equations also had a more stable performance across mGFR, age and BMI intervals, generally with P-30 >= 90% and never <80%. Combined equations reached P-30 of 95% when the difference between eGFR(CREA) and eGFR(CYSC) was <10% but decreased to 82% at a difference of >= 40%. Conclusions: Combining cystatin C and creatinine assays improves GFR estimations with P-30 >= 90% in adults. Reporting estimates of both single and combined marker equations in clinical settings makes it possible to assess the validity of the combined equation based on the agreement between the single marker equations.
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| 3. |
- Dardashti, Alain, et al.
(författare)
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Shrunken Pore Syndrome is associated with a sharp rise in mortality in patients undergoing elective coronary artery bypass grafting.
- 2016
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 76:1, s. 74-81
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Tidskriftsartikel (refereegranskat)abstract
- Shrunken Pore Syndrome was recently suggested for the pathophysiologic state in patients characterized by an estimation of their glomerular filtration rate (GFR) based upon cystatin C, which is lower or equal to 60% of their estimated GFR based upon creatinine, i.e. when eGFRcystatin C ≤ 60% of eGFRcreatinine. Not only the cystatin C level, but also the levels of other low molecular mass proteins are increased in this condition. The preoperative plasma levels of cystatin C and creatinine were measured in 1638 patients undergoing elective coronary artery bypass grafting. eGFRcystatin C and eGFRcreatinine were calculated using two pairs of estimating equations, CAPA and LMrev, and CKD-EPIcystatin C and CKD-EPIcreatinine, respectively. The Shrunken Pore Syndrome was present in 2.1% of the patients as defined by the CAPA and LMrev equations and in 5.7% of the patients as defined by the CKD-EPIcystatin C and CKD-EPIcreatinine equations. The patients were studied over a median follow-up time of 3.5 years (2.0-5.0 years) and the mortality determined. Shrunken Pore Syndrome defined by both pairs of equations was a strong, independent, predictor of long-term mortality as evaluated by Cox analysis and as illustrated by Kaplan-Meier curves. Increased mortality was observed also for the subgroups of patients with GFR above or below 60 mL/min/1.73 m(2). Changing the cut-off level from 60 to 70% for the CAPA and LMrev equations increased the number of patients with Shrunken Pore Syndrome to 6.5%, still displaying increased mortality.
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| 4. |
- Nyman, Ulf, et al.
(författare)
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The revised Lund-Malmo GFR estimating equation outperforms MDRD and CKD-EPI across GFR, age and BMI intervals in a large Swedish population
- 2014
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 52:6, s. 815-824
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Tidskriftsartikel (refereegranskat)abstract
- Background: The performance of creatinine-based glomerular filtration rate (GFR) estimating equations may vary in subgroups defined by GFR, age and body mass index (BMI). This study compares the performance of the Modification of Diet in Renal Disease (MDRD) study and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations with the revised Lund-Malmo equation (LM Revised), a new equation that can be expected to handle changes in GFR across the life span more accurately. Methods: The study included 3495 examinations in 2847 adult Swedish patients referred for measurement of GFR (mGFR) 2008-2010 by plasma clearance of iohexol (median 52 mL/min/1.73 m(2)). Bias, precision [interquartile range (IQR)] and accuracy [percentage of estimates +/- 10% (P-10) and +/- 30% (P-30) of mGFR] were compared. Results: The overall results of LM Revised/MDRD/CKD-EPI were: median bias 2%/8%/11%, IQR 12/14/14 mL/min/1.73 m(2), P-10 40%/35%/35% and P-30 84%/75%/76%. LM Revised was the most stable equation in terms of bias, precision and accuracy across mGFR, age and BMI intervals irrespective of gender. MDRD and CKD-EPI overestimated mGFR in patients with decreased kidney function, young adults and elderly. All three equations overestimated mGFR and had low accuracy in patients with BMI <20 kg/m(2), most pronounced among men. Conclusions: In settings similar to the investigated cohort LM Revised should be preferred to MDRD and CKD-EPI due to its higher accuracy and more stable performance across GFR, age and BMI intervals.
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| 5. |
- Pottel, Hans, et al.
(författare)
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Standardization of serum creatinine is essential for accurate use of unbiased estimated GFR equations : evidence from three cohorts matched on renal function
- 2022
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Ingår i: Clinical Kidney Journal. - : Oxford University Press. - 2048-8505 .- 2048-8513. ; 15:12, s. 2258-2265
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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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| 6. |
- Björck, Lars, et al.
(författare)
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Bacterial growth inhibited by a synthetic inhibitor based upon the structure of a human proteinase inhibitor
- 1989
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 337:6205, s. 385-386
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Tidskriftsartikel (refereegranskat)abstract
- Cysteine proteinases are important not only in the intracellular catabolism of peptides and proteins1 and in the processing of prohormones and proenzymes2,3, but also in the penetration of normal human tissue by malignant cells4 and possibly microorganisms5, including viruses. Cystatin C is a human cysteine proteinase inhibitor present in extracellular fluids6. We have synthesized peptide derivatives mimicking the proposed proteinase-binding centre of cystatin C7 and find that they irreversibly inhibit cysteine proteinases. Several bacteria produce proteinases, so we tested a tripeptide derivative (Z-LVG-CHN2) for in vitro anti-bacterial activity against a large number of bacterial strains belonging to thirteen different species. It was found to inhibit specifically the growth of all strains of group A streptococci. The susceptibility of these human pathogens to the peptide was compared with that to well-established anti-streptococcal antibiotics such as tetracy-cline and bacitracin. Moreover, the peptide was active in vivo against group A streptococci: mice injected with lethal doses of these bacteria were cured by a single injection of Z-LVG-CHN2. The cysteine proteinase produced by group A streptococci was isolated and found to be inhibited by Z-LVG-CHN2; moreover, excess proteinase relieved the growth inhibition caused by the peptide derivative, suggesting that the antibacterial activity of Z-LVG-CHN2 is due to inhibition of this cysteine proteinase. This strategy of blocking proteinases with peptide derivatives that mimic naturally occurring inhibitors could be useful in the construction of new agents against other microorganisms, including viruses.
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| 7. |
- Ranheimer Östner, Gustav, et al.
(författare)
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Stabilization, Characterization and Selective Removal of Cystatin C Amyloid Oligomers.
- 2013
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 288:23, s. 16438-16450
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Tidskriftsartikel (refereegranskat)abstract
- The pathophysiological process in amyloid disorders usually involves the transformation of a functional monomeric protein via potentially toxic oligomers into amyloid fibrils. The structure and properties of the intermediary oligomers have been difficult to study due to their instability and dynamic equilibrium with smaller and larger species. In hereditary cystatin C amyloid angiopathy, a cystatin C variant is deposited in arterial walls and cause brain hemorrhage in young adults. In the present investigation, we use redox experiments of monomeric cystatin C, stabilized against domain swapping by an intramolecular disulfide bond, to generate stable oligomers (dimers, trimers, tetramers, decamers and high molecular weight oligomers). These oligomers were characterized concerning size by gel filtration, polyacrylamide gel electrophoresis and mass spectrometry, concerning shape by electron and atomic force microscopy, and, concerning function, by assays of their capacity to inhibit proteases. The results showed the oligomers to be highly ordered, domainswapped assemblies of cystatin C and that the oligomers could not build larger oligomers, or fibrils, without domain swapping. The stabilized oligomers were used to induce antibody formation in rabbits. After immunosorption, using immobilized monomeric cystatin C, and elution from columns with immobilized cystatin C oligomers, oligomer-specific antibodies were obtained. These could be used to selectively remove cystatin C dimers from biological fluids containing both dimers and monomers.
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| 8. |
- Björk, Jonas, et al.
(författare)
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GFR estimation based on standardized creatinine and cystatin C : A European multicenter analysis in older adults
- 2018
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter GmbH. - 1437-4331 .- 1434-6621. ; 56:3, s. 422-435
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Tidskriftsartikel (refereegranskat)abstract
- Although recommended by the Kidney Disease Improving Global Outcomes, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPICR) creatinine equation was not targeted to estimate glomerular filtration rate (eGFR) among older adults. The Berlin Initiative Study (BIS1CR) equation was specifically developed in older adults, and the Lund-Malmö revised (LMRCR) and the Full Age Spectrum (FASCR) equations have shown promising results in older adults. Our aim was to validate these four creatinine equations, including addition of cystatin C in a large multicenter cohort of Europeans ≥70 years. A total of 3226 individuals (2638 with cystatin C) underwent GFR measurement (mGFR; median, 44 mL/min/1.73 m2) using plasma iohexol clearance. Bias, precision (interquartile range [IQR]), accuracy (percent of estimates ±30% of mGFR, P30), eGFR accuracy diagrams and probability diagrams to classify mGFR<45 mL/min/1.73 m2 were compared. The overall results of BIS1CR/CKD-EPICR/FASCR/LMRCR were as follows: median bias, 1.7/3.6/0.6/-0.7 mL/min/1.73 m2; IQR, 11.6/12.3/11.1/10.5 mL/min/1.73 m2; and P30, 77.5%/76.4%/80.9%/83.5% (significantly higher for LMR, p<0.001). Substandard P30 (<75%) was noted for all equations at mGFR<30 mL/min/1.73 m2, and at body mass index values <20 and ≥35 kg/m2. LMRCR had the most stable performance across mGFR subgroups. Only LMRCR and FASCR had a relatively constant small bias across eGFR levels. Probability diagrams exhibited wide eGFR intervals for all equations where mGFR<45 could not be confidently ruled in or out. Adding cystatin C improved P30 accuracy to 85.7/86.8/85.7/88.7 for BIS2CR+CYS/CKD-EPICR+CYS/FASCR+CYS/MEANLMR+CAPA. LMRCR and FASCR seem to be attractive alternatives to CKD-EPICR in estimating GFR by creatinine-based equations in older Europeans. Addition of cystatin C leads to important improvement in estimation performance.
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| 9. |
- Grubb, Anders, et al.
(författare)
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Abnormal Metabolism of γ-Trace Alkaline Microprotein : The Basic Defect in Hereditary Cerebral Hemorrhage with Amyloidosis
- 1984
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 311:24, s. 1547-1549
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Tidskriftsartikel (refereegranskat)abstract
- ALTHOUGH the total incidence of cerebral hemorrhage is high, comparatively few reports concerning the familial occurrence of this disease have been published.1,2 In 1935 Arnason described 10 families with a high incidence of cerebral hemorrhage and concluded that a hereditary form of the disease was present in these families.3 Further clinicopathological investigations of the disease revealed an autosomal dominant inheritance and a connection between the disease and a special form of amyloidosis confined to the cerebral vasculature.4 This type of cerebral hemorrhage is therefore generally referred to as hereditary cerebral hemorrhage with amyloidosis. Recently, the fibrillar components of the amyloid.
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| 10. |
- Grubb, Anders, et al.
(författare)
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First certified reference material for cystatin C in human serum ERM-DA471/IFCC.
- 2010
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Ingår i: Clinical Chemistry and Laboratory Medicine. - 1434-6621. ; 48:11, s. 1619-1621
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Tidskriftsartikel (refereegranskat)abstract
- The IFCC Working Group for the Standardisation of Cystatin C (WG-SCC), in collaboration with the Institute for Reference Materials and Measurements (IRMM), announces the availability of the new certified reference material ERM-DA471/IFCC. The material was characterised using a pure protein primary reference preparation (PRP) as calibrant. The PRP was prepared from recombinant cystatin C, and its concentration measured using dry mass determination. The characterisation of ERM-DA471/IFCC was performed by particle enhanced immuno-nephelometry, particle enhanced immuno-turbidimetry, and enzyme amplified single radial immuno-diffusion. The certified cystatin C mass concentration in ERM-DA471/IFCC, if reconstituted according to the specified procedure, is 5.48 mg/L, the expanded uncertainty (k=2) being 0.15 mg/L.
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