| 1. |
- Grubb, Anders, et al.
(författare)
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Simple Cystatin C-Based Prediction Equations for Glomerular Filtration Rate Compared with the Modification of Diet in Renal Disease Prediction Equation for Adults and the Schwartz and the Counahan-Barratt Prediction Equations for Children.
- 2005
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 51:8, s. 1420-1431
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Serum creatinine is the most commonly used marker for estimation of glomerular filtration rate (GFR). To compensate for its drawbacks as a GFR marker, several prediction equations including several parameters are being used, with the Modification of Diet in Renal Disease (MDRD), Schwartz, and Counahan-Barratt equations being the ones most widely accepted for estimation of relative GFR in mL x min(-1) x (1.73 m(2))(-1). The present study analyzes whether these GFR prediction equations for adults and children might be replaced by simple prediction equations based on plasma concentrations of cystatin C.METHODS: Data from 536 patients (0.3-93 years), consecutively referred for determination of GFR by an invasive gold standard procedure, were used for the analysis. Calculations of bias (median percentage of error), correlation (adjusted R(2)), and percentage of estimates within 30% and 50% of measured GFR were used in the comparisons.RESULTS: A cystatin C-based prediction equation using only concentration in mg/L and a prepubertal factor: GFR [mL x min(-1) x (1.73 m(2))(-1)] = 84.69 x cystatin C (mg/L)(-1.680) x 1.384 (if a child <14 years) assessed GFR equally well or better than the simplified MDRD, the Schwartz, and the Counahan-Barratt prediction equations for the adult (> or =18 years) and juvenile groups of the investigated cohort. Age did not influence the cystatin C-based prediction equation for adults, whereas gender did, but with a factor close to unity (0.948 for females).CONCLUSION: A GFR prediction equation based solely on cystatin C (in mg/L) and a prepubertal factor might replace the simplified MDRD prediction equation for adults and the Schwartz and Counahan-Barratt prediction equations for children.
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| 2. |
- Lindström, Veronica, et al.
(författare)
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Different elimination patterns of beta-trace protein, beta(2)-microglobulin and cystatin C in haemodialysis, haemodiafiltration and haemofiltration.
- 2008
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 68, s. 685-691
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Low molecular mass proteins (LMMP) are putative uraemic toxins, but their elimination is negligible in standard haemodialysis (HD). In this study, we used beta(2)-microglobulin, cystatin C and beta-trace protein, which differ in molecular mass and charge, to characterize the elimination patterns of three different dialysis modalities. Material and methods. Plasma samples were obtained at the start, 30 min after the start, at the end of the dialysis treatment and 30 min after termination of the dialysis session. Seventeen patients were treated with low-flux HD, 13 with post-dilution haemodiafiltration (HDF) and 8 with pre-dilution haemofiltration (HF). The changes in concentrations of the three LMMPs were monitored and expressed as percentages of the concentrations at the start of treatments. Results. Conventional HD with low-flux membranes showed a high elimination of small molecules (urea and creatinine), but did not reduce the levels of the three LMMPs studied. During HDF and HF, there was a significant decrease in the plasma levels of cystatin C (to 28 % and 44 %, respectively) (p<0.001) and of beta(2)-microglobulin (to 23 % and 33 %, respectively) (p<0.001). However, the level of beta-trace protein was significantly reduced (to 65 %) only after HDF. Conclusions . The three dialysis modalities showed significantly different elimination patterns for the LMMPs studied. Elimination of beta-trace protein was lower than those of cystatin C and beta(2)-microglobulin both in HDF and HF. beta-trace protein was only moderately eliminated by HDF and not at all by HF, and may be a useful marker in the evaluation of different convective therapies.
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| 3. |
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| 4. |
- Bakoush, Omran, et al.
(författare)
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Inaccuracy of GFR predictions by plasma cystatin C in patients without kidney dysfunction and in advanced kidney disease.
- 2008
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Ingår i: Clinical Nephrology. - 0301-0430. ; 69:5, s. 331-338
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In clinical practice there is need for a simple and reliable test for determination of impaired renal function. With reductions in GFR, the plasma cystatin C concentration (C, mg/l) will increase earlier than serum creatinine, and it is generally agreed that plasma cystatin C is only little affected by body weight, age or sex. However, some reports indicate that cystatin C may be influenced not only by GFR, but also by malignancy, inflammation and high doses of corticosteroids. The aim of the present study was to investigate how plasma cystatin C predicts GFR in distinct subcategories of patients with various disorders as well as in organ transplant patients. METHODS: Plasma cystatin C was measured in 536 patients (age range 0.3-96 years, 262 females, 274 males), consecutively referred to our hospital for determination of GFR by iohexol clearance. Correlations of log GFR vs. log cystatin C were used to compare plasma cystatin C and measured GFR for the following categories: individuals with no known kidney disease (No-KD), malignant patients with (mostly) normal GFR, solid organ-transplanted patients, and patients with native chronic kidney disease (CKD). RESULTS: In patients with normal kidney function and cystatin C level GFR>30 ml/min(-1) (1.73 m2)(-1)) or solid organ transplantation (GFR=84.55 C(1.7666) and GFR=83.95(C-1.5968), respectively). CONCLUSION: Therefore, for these categories, a common equation for all patients with increased cystatin C, irrespective of cause of renal impairment, could be used, namely that presented by Grubb et al. [2005] (GFR=83.93(C-1.676)). However, at marked reductions of renal function (GFR<30 or cystatin C>2), i.e. for CKD Stages 4 and 5, the Grubb prediction equation is less accurate. Based on our data, we suggest the equation GFR=50.52 C(-1.26) for this category of patients.
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| 5. |
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| 6. |
- Bengtsson, Eva, et al.
(författare)
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Lack of the Cysteine-Protease Inhibitor Cystatin C Promotes Atherosclerosis in Apolipoprotein E-Deficient Mice.
- 2005
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1524-4636. ; 25:10, s. 2151-2156
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Tidskriftsartikel (refereegranskat)abstract
- Objective - Degradation of extracellular matrix plays an important role in growth and destabilization of atherosclerotic plaques. Cystatin C, inhibitor of the collagen- and elastin-degrading cysteine proteases of the cathepsin family, is produced by virtually all cell types. It is present in the normal artery wall but severely reduced in human atherosclerotic lesions. Methods and Results - To determine the functional role of cystatin C in atherosclerosis, we crossed cystatin C - deficient ( cysC(-/-)) mice with apolipoprotein E - deficient ( apoE(-/-)) mice. After 25 weeks of atherogenic diet, mice lacking apoE and cystatin C (cysC(-/-) apoE(-/-)) had larger subvalvular plaques compared with cysC(+/+) apoE(-/-) mice (766 000 +/- 20 000 mu m(2) per section versus 662 000 +/- 19 000 mu m(2) per section; P = 0.001), suggesting an atheroprotective role of cystatin C. The plaques from cysC(-/-) apoE(-/-) mice were characterized by increased total macrophage content. To determine which cellular source is important for the antiatherosclerotic effect of cystatin C, we performed bone marrow transplantations. ApoE(-/-) mice were transplanted with either cysC(-/-) apoE(+/+) or cysC(+/+) apoE(-/-) bone marrow. No significant differences in plaque area, macrophage, collagen, or lipid content of subvalvular lesions between the 2 groups were detected. Conclusions - The result suggests that the protective role of cystatin C in atherosclerosis is dependent primarily on its expression in nonhematopoietic cell types.
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| 7. |
- Björk, Jonas, et al.
(författare)
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Prediction of relative glomerular filtration rate in adults: New improved equations based on Swedish Caucasians and standardized plasma-creatinine assays.
- 2007
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 67:7, s. 678-695
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate newly developed equations predicting relative glomerular filtration rate(GFR) in adult Swedish Caucasians and to compare with the Modification of Diet in Renal Disease(MDRD) and Mayo Clinic equations using enzymatic and zero-calibrated plasma creatinine assays. MATERIAL AND METHODS: GFR was measured with iohexol clearance adjusted to 1.73 m(2). One population sample (n=436/Lund) was used to derive an equation based on plasma-creatinine/age/gender, and a second with the addition of lean body mass (LBM). Both equations were validated in a separate sample (n=414/Malmö). The coefficients of the equations were eventually fine-tuned using all 850 patients and yielding Lund-Malmö equations without (LM) and with LBM-term (LM(LBM)).Their performance was compared with the MDRD(CC) (conventional creatinine calibration), MDRD(IDMS) (isotope dilution mass spectroscopy traceable calibration) and Mayo Clinic equations. RESULTS: The Lund equations performed similarly in both samples. In the combined set, the Mayo Clinic/MDRD(CC) resulted in +19.0/+10.2 % median bias, while bias for the other equations was < 10 %. LM(LBM) had the highest accuracy (86 % of estimates within 30 % of measured GFR), significantly (p < 0.001) better than for MDRD(IDMS) (80 %). In men with BMI < 20 kg/m(2), MDRD(IDMS)/LM had +46 %/+19 % median bias. MDRD(IDMS) also overestimated GFR by 22 %/14 % in men/women above 80 years of age. The LM(LBM) equation had < 10 % bias irrespective of BMI, age or GFR except for a 15 % negative bias at GFR > 90 mL/min/1.73 m(2). CONCLUSION: The newly developed Lund-Malmö equations for GFR estimation performed better than the MDRD(IDMS) and Mayo Clinic equations in a Swedish Caucasian sample. Inclusion of an LBM term improved performance markedly in certain subgroups.
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| 8. |
- Björk, Jonas, et al.
(författare)
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Variability in diagnostic accuracy can be estimated using simple population weighting.
- 2009
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Ingår i: Journal of Clinical Epidemiology. - : Elsevier BV. - 1878-5921 .- 0895-4356. ; 62:1, s. 54-57
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Diagnostic accuracy of a quantitative diagnostic test at a given numeric cutoff is dependent on the type of population (e.g., chronic, referrals, or screening) under investigation. Simple weighted averages calculated from a single study sample may be used to assess variability in accuracy in different types of populations. STUDY DESIGN AND SETTING: We evaluated the accuracy of the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation as a diagnostic test to separate stage 1 and 2 chronic kidney disease (>or=60 mL/min per 1.73 m(2)) from stage 3-5 (<60 mL/min per 1.73 m(2) requiring treatment to prevent progression) in a sample of 850 patients referred for determination of glomerular filtration rate (GFR). Using population weighting, we also estimated the accuracy of the MDRD equation when the GFR distribution typically found in screening situations was mimicked. RESULTS: Estimated diagnostic accuracy of the MDRD equation varied substantially for different population types (sensitivity range 82%-97%, specificity 67%-93%; figures include the original MDRD study). CONCLUSIONS: Reports of diagnostic accuracy should include estimates of the variability of diagnostic accuracy, using different real or tentative population distributions. Population weighting is a useful tool for this purpose.
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| 9. |
- Blirup, Soren, et al.
(författare)
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Standardization of Cystatin C: development of primary and secondary reference preparations.
- 2008
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 68:s241, s. 67-70
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Tidskriftsartikel (refereegranskat)abstract
- A Primary Reference Preparation has been produced using pure, recombinant, Cystatin C in a solvent of 0.1 mol/L KCl. Dry mass determination of the Primary Reference Preparation resulted in a Cystatin C concentration of 5.20 g/L. Agarose-electrophoresis and SDS-electrophoresis, as well as N-terminal sequencing, verified the purity, homogeneity and identity of Cystatin C in the Primary Reference Preparation. For the Secondary Reference Preparation, a serum pool was collected and stabilized. A pilot batch was made to verify the selected procedure and spiking with the pure, recombinant Cystatin C. The final Secondary Reference Preparation is now produced (4468 vials) and ready for value assignment and further characterization.
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| 10. |
- Bokarewa, Maria, 1963, et al.
(författare)
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Cystatin C binds serum amyloid A, downregulating its cytokine-generating properties
- 2007
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Ingår i: Journal of Rheumatology. - 0315-162X. ; 34:6, s. 1293-1301
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To assess the interaction between cystatin C (CysC) and serum amyloid A protein (SAA). Methods. Levels of CysC and SAA and antibodies against these proteins were assessed in the paired blood and synovial fluid (SF) samples of 90 patients with rheumatoid arthritis (RA). Age and sex matched individuals having normal iohexol clearance (n = 90) and SF following joint trauma (n = 40) were used as controls. In vitro experiments included assessment of interaction between CysC and SAA by ELISA and the influence of CysC on SAA functions. Results. A pilot screening for cystatins C, E, and F in blood and SF of patients with RA found CysC to be by far the predominant extracellular cystatin. Circulating CysC levels were significantly lower in patients with RA compared to the matched controls (0.81 +/- 0.03 vs 1.01 +/- 0.03 mg/l; p = 0.05). These low CysC levels could not be explained by the presence of anti-CysC antibodies in patients with RA. In contrast, concentrations of CysC that accumulated in the inflamed SF were significantly greater in patients with erosive RA (1.66 +/- 0.08 mg/l) compared to nonerosive RA (1.36 +/- 0.06 mg/l; p = 0.003) and controls (1.18 +/- 0.03 mg/l; p = 0.043). In vitro studies showed direct binding of CysC to SAA. CysC/SAA binding impaired proinflammatory effects of SAA, reducing its ability to trigger expression of proinflammatory cytokines. Conclusion. Our study shows a relative deficiency of circulating CysC during systemic inflammation in RA. Physical interaction between CysC and the acute-phase protein SAA (1) provides an explanation for CysC deficiency; and (2) suggests that CysC is regulating inflammatory responses. We hypothesize that decreased systemic CysC levels predispose to accelerated atherosclerosis and development of amyloidosis in patients with RA.
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