| 1. |
- Noppe, Wim, et al.
(författare)
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Chromato-panning: an efficient new mode of identifying suitable ligands from phage display libraries
- 2009
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Ingår i: BMC Biotechnology. - : Springer Science and Business Media LLC. - 1472-6750. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Phage Display technology is a well established technique for high throughput screening of affinity ligands. Here we describe a new compact chromato-panning procedure for selection of suitable binders from a phage peptide display library. Results: Both phages and E. coli cells pass non-hindered through the interconnected pores of macroporous gel, so called cryogel. After coupling a ligand to a monolithic cryogel column, the phage library was applied on the column and non-bound phages were washed out. The selection of strong phage-binders was achieved already after the first panning cycle due to the efficient separation of phage-binders from phage-non-binders in chromatographic mode rather than in batch mode as in traditional biopanning procedures. E. coli cells were applied on the column for infection with the specifically bound phages. Conclusion: Chromato-panning allows combining several steps of the panning procedure resulting in 4-8 fold decrease of total time needed for phage selection.
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| 2. |
- Björk, Jonas, et al.
(författare)
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A novel method for creatinine adjustment makes the revised Lund-Malmö GFR estimating equation applicable in children
- 2020
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 80:6, s. 456-463
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to establish creatinine growth curves separately for males and females that can be used to adjust childhood levels of serum creatinine to corresponding adult levels. Linear regression with fractional polynomials of age as independent variable was used to construct creatinine growth curves for a reference cohort (n = 83,157 samples from Belgium and Sweden, age 2-40 years). Adjusted creatinine obtained from the growth curves was used to improve accuracy of estimated glomerular filtration rate (eGFR) based on the Lund-Malmö revised (LMR) equation in children. The LMR equation based on creatinine values adjusted to age 18 years was validated against measured GFR (mGFR) in a separate cohort of 4005 children from four different European countries. Validation metrics included median bias, precision, and accuracy expressed as percentage of estimates within ±30% (P30) of mGFR. Remarkable improvements in bias and accuracy were observed; P30 increased from 56% to 74% after creatinine adjustments in children with mGFR <75 mL/min/1.73 m2 (n = 932), while P30 was relatively unchanged (89-90%) at mGFR ≥75 mL/min/1.73 m2 (n = 3073). The suggested approach with adjusted creatinine makes LMR applicable in children irrespective of their renal function.
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| 3. |
- Björk, Jonas, et al.
(författare)
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Estimation of the glomerular filtration rate in children and young adults by means of the CKD-EPI equation with age-adjusted creatinine values
- 2021
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Ingår i: Kidney International. - : Elsevier BV. - 0085-2538. ; 99:4, s. 940-947
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Tidskriftsartikel (refereegranskat)abstract
- The CKD-EPI creatinine-based estimation equation for glomerular filtration rate (GFR) cannot be used in children, overestimates GFR in young adults, and its combination with the KDIGO recommended pediatric CKiD (Schwartz bedside) equation causes implausible increases in estimated GFR when switching from pediatric to adult care. By establishing sex-specific creatinine growth curves for children and young adults, creatinine levels of children and young adults below age 40 years were adjusted with 40 as assigned age and applied in the CKD-EPI equation. Validation was performed in 4005 children (2–17 years) and 3309 young adults (18–39 years) using metrics based on bias, precision, and accuracy including percentage of estimates within 30% (P30) of measured GFR (mGFR). Comparisons were made with the CKiD and Schwartz-Lyon equations in children. CKD-EPI with age-adjusted creatinine instead of actual age and creatinine led to extensive improvements in bias, precision, and accuracy at all ages, in both sexes and at all levels of mGFR. At mGFR below and above 75 mL/min/1.73m2, the P30 increased from 12% to 75% and 33% to 88% in children, respectively, and from 56% to 73% and 83% to 92% in young adults, respectively. In children adjusted CKD-EPI was more accurate than CKiD, especially above mGFR 75 mL/min/1.73m2 (P30 88% vs. 82%), while Schwartz-Lyon was more accurate than adjusted CKD-EPI at mGFR below 75 mL/min/1.73m2 (P30 81% vs. 75%). Thus, the proposed strategy based on age-adjusted creatinine in children and young adults makes the CKD-EPI equation applicable across the full spectrum of age and kidney function.
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| 4. |
- Björk, Jonas, et al.
(författare)
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Estimation of the glomerular filtration rate in children and young adults using the CKD-EPI equation with age-adjusted creatinine values
- 2021
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Ingår i: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 99:4, s. 940-947
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Tidskriftsartikel (refereegranskat)abstract
- The CKD-EPI creatinine-based estimation equation for glomerular filtration rate (GFR) cannot be used in children, overestimates GFR in young adults, and its combination with the KDIGO recommended pediatric CKiD (Schwartz bedside) equation causes implausible increases in estimated GFR when switching from pediatric to adult care. By establishing sex-specific creatinine growth curves for children and young adults, creatinine levels of children and young adults below age 40 years were adjusted with 40 as assigned age and applied in the CKD-EPI equation. Validation was performed in 4005 children (2-17 years) and 3309 young adults (18-39 years) using metrics based on bias, precision, and accuracy including percentage of estimates within 30% (P30) of measured GFR (mGFR). Comparisons were made with the CKiD and Schwartz-Lyon equations in children. CKD-EPI with age-adjusted creatinine instead of actual age and creatinine led to extensive improvements in bias, precision, and accuracy at all ages, in both sexes and at all levels of mGFR. At mGFR below and above 75 mL/min/1.73m2, the P30 increased from 12% to 75% and 33% to 88% in children, respectively, and from 56% to 73% and 83% to 92% in young adults, respectively. In children adjusted CKD-EPI was more accurate than CKiD, especially above mGFR 75 mL/min/1.73m2 (P30 88% vs. 82%), while Schwartz-Lyon was more accurate than adjusted CKD-EPI at mGFR below 75 mL/min/1.73m2 (P30 81% vs. 75%). Thus, the proposed strategy based on age-adjusted creatinine in children and young adults makes the CKD-EPI equation applicable across the full spectrum of age and kidney function.
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| 5. |
- Björk, Jonas, et al.
(författare)
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Prospects for improved glomerular filtration rate estimation based on creatinine—results from a transnational multicentre study
- 2020
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Ingår i: Clinical Kidney Journal. - : Oxford University Press (OUP). - 2048-8505 .- 2048-8513. ; 13:4, s. 674-683
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Tidskriftsartikel (refereegranskat)abstract
- Background The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation is routinely used to assess renal function but exhibits varying accuracy depending on patient characteristics and clinical presentation. The overall aim of the present study was to assess if and to what extent glomerular filtration rate (GFR) estimation based on creatinine can be improved.MethodsIn a cross-sectional analysis covering the years 2003–17, CKD-EPI was validated against measured GFR (mGFR; using various tracer methods) in patients with high likelihood of chronic kidney disease (CKD; five CKD cohorts, n = 8365) and in patients with low likelihood of CKD (six community cohorts, n = 6759). Comparisons were made with the Lund–Malmö revised equation (LMR) and the Full Age Spectrum equation.Results7In patients aged 18–39 years old, CKD-EPI overestimated GFR with 5.0–16 mL/min/1.73 m2 in median in both cohort types at mGFR levels <120 mL/min/1.73 m2. LMR had greater accuracy than CKD-EPI in the CKD cohorts (P30, the percentage of estimated GFR within 30% of mGFR, 83.5% versus 76.6%). CKD-EPI was generally the most accurate equation in the community cohorts, but all three equations reached P30 above the Kidney Disease Outcomes Quality Initiative benchmark of 90%.ConclusionsNone of the evaluated equations made optimal use of available data. Prospects for improved GFR estimation procedures based on creatinine exist, particularly in young adults and in settings where patients with suspected or manifest CKD are investigated.
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| 6. |
- Björk, Jonas, et al.
(författare)
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Validation of standardized creatinine and cystatin C GFR estimating equations in a large multicentre European cohort of children
- 2019
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Ingår i: Pediatric Nephrology. - : Springer Science and Business Media LLC. - 0931-041X .- 1432-198X.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Most validations of paediatric glomerular filtration rate (GFR) estimating equations using standardized creatinine (CR) and cystatin C (CYS) assays have comprised relatively small cohorts, which makes accuracy across subgroups of GFR, age, body mass index (BMI) and gender uncertain. To overcome this, a large cohort of children referred for GFR determination has been established from several European medical centres. Methods: Three thousand four hundred eight measurements of GFR (mGFR) using plasma clearance of exogenous substances were performed in 2218 children aged 2–17 years. Validated equations included Schwartz-2009CR/2012CR/CYS/CR+CYS, FASCR/CYS/CR+CYS, LMRCR, Schwartz-LyonCR, BergCYS, CAPACYS, CKD-EPICYS, AndersenCR+CYS and arithmetic means of the best single-marker equations in explorative analysis. Five metrics were used to compare the performance of the GFR equations: bias, precision and three accuracy measures including the percentage of GFR estimates (eGFR) within ± 10% (P10) and ± 30% (P30) of mGFR. Results: Three of the cystatin C equations, BergCYS, CAPACYS and CKD-EPICYS, exhibited low bias and generally satisfactory accuracy across all levels of mGFR; CKD-EPICYS had more stable performance across gender than the two other equations. Among creatinine equations, Schwartz-LyonCR had the best performance but was inaccurate at mGFR < 30 mL/min/1.73 m2 and in underweight patients. Arithmetic means of the best creatinine and cystatin C equations above improved bias compared to the existing composite creatinine+cystatin C equations. Conclusions: The present study strongly suggests that cystatin C should be the primary biomarker of choice when estimating GFR in children with decreased GFR. Arithmetic means of well-performing single-marker equations improve accuracy further at most mGFR levels and have practical advantages compared to composite equations.
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| 7. |
- Delanaye, Pierre, et al.
(författare)
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Age-adapted percentiles of measured glomerular filtration in healthy individuals : extrapolation to living kidney donors over 65 years.
- 2022
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter. - 1434-6621 .- 1437-4331. ; 60:3, s. 401-407
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Most data on glomerular filtration rate (GFR) originate from subjects <65 years old, complicating decision-making in elderly living kidney donors. In this retrospective multi-center study, we calculated percentiles of measured GFR (mGFR) in donors <65 years old and extrapolated these to donors ≥65 years old.METHODS: mGFR percentiles were calculated from a development cohort of French/Belgian living kidney donors <65 years (n=1,983), using quantiles modeled as cubic splines (two linear parts joining at 40 years). Percentiles were extrapolated and validated in an internal cohort of donors ≥65 years (n=147, France) and external cohort of donors and healthy subjects ≥65 years (n=329, Germany, Sweden, Norway, France, The Netherlands) by calculating percentages within the extrapolated 5th-95th percentile (P5-P95).RESULTS: Individuals in the development cohort had a higher mGFR (99.9 ± 16.4 vs. 86.4 ± 14 and 82.7 ± 15.5 mL/min/1.73 m2) compared to the individuals in the validation cohorts. In the internal validation cohort, none (0%) had mGFR below the extrapolated P5, 12 (8.2%) above P95 and 135 (91.8%) between P5-P95. In the external validation cohort, five subjects had mGFR below the extrapolated P5 (1.5%), 25 above P95 (7.6%) and 299 (90.9%) between P5-P95.CONCLUSIONS: We demonstrate that extrapolation of mGFR from younger donors is possible and might aid with decision-making in elderly donors.
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| 8. |
- Delanaye, Pierre, et al.
(författare)
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CKD : A Call for an Age-Adapted Definition
- 2019
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673. ; 30:10, s. 1785-1805
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Forskningsöversikt (refereegranskat)abstract
- Current criteria for the diagnosis of CKD in adults include persistent signs of kidney damage, such as increased urine albumin-to-creatinine ratio or a GFR below the threshold of 60 ml/min per 1.73 m2 This threshold has important caveats because it does not separate kidney disease from kidney aging, and therefore does not hold for all ages. In an extensive review of the literature, we found that GFR declines with healthy aging without any overt signs of compensation (such as elevated single-nephron GFR) or kidney damage. Older living kidney donors, who are carefully selected based on good health, have a lower predonation GFR compared with younger donors. Furthermore, the results from the large meta-analyses conducted by the CKD Prognosis Consortium and from numerous other studies indicate that the GFR threshold above which the risk of mortality is increased is not consistent across all ages. Among younger persons, mortality is increased at GFR <75 ml/min per 1.73 m2, whereas in elderly people it is increased at levels <45 ml/min per 1.73 m2 Therefore, we suggest that amending the CKD definition to include age-specific thresholds for GFR. The implications of an updated definition are far reaching. Having fewer healthy elderly individuals diagnosed with CKD could help reduce inappropriate care and its associated adverse effects. Global prevalence estimates for CKD would be substantially reduced. Also, using an age-specific threshold for younger persons might lead to earlier identification of CKD onset for such individuals, at a point when progressive kidney damage may still be preventable.
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| 9. |
- Delanaye, Pierre, et al.
(författare)
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Performance of creatinine-based equations to estimate glomerular filtration rate in White and Black populations in Europe, Brazil, and Africa.
- 2022
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Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A new Chronic Kidney Disease Epidemiology equation without race variable has been recently proposed (CKD-EPIAS). This equation has neither been validated outside USA nor compared to the new European Kidney Function Consortium (EKFC) and Lund-Malmö Revised (LMREV) equations, developed in European cohorts.METHODS: Standardized creatinine and measured glomerular filtration rate (GFR) from the European EKFC cohorts (n = 13 856 including 6031 individuals in the external validation cohort), from France, (n = 4429, including 964 Black Europeans), from Brazil (n = 100), and from Africa (n = 508) were used to test the performances of the equations. A matched analysis between White Europeans and Black Africans or Black Europeans was performed.RESULTS: In White Europeans (n = 9496), both the EKFC and LMREV equations outperformed CKD-EPIAS (bias of -0.6 and -3.2, respectively versus 5.0 mL/min/1.73m², and accuracy within 30% of 86.9 and 87.4, respectively versus 80.9%). In Black Europeans and Black Africans, the best performance was observed with the EKFC equation using a specific Q-value ( = concentration of serum creatinine in healthy males and females). These results were confirmed in matched analyses, which showed that serum creatinine concentrations were different in White Europeans, Black Europeans, and Black Africans for the same measured GFR, age, sex and body mass index. Creatinine differences were more relevant in males.CONCLUSION: In a European and African cohort, the performances of CKD-EPIAS remain suboptimal. The EKFC equation, using usual or dedicated, population-specific Q-values presents the best performance in the whole age range in the European and African populations included in this study.
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| 10. |
- Delanaye, Pierre, et al.
(författare)
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Performance of creatinine-based equations to estimate glomerular filtration rate with a methodology adapted to the context of drug dosage adjustment
- 2022
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Ingår i: British Journal of Clinical Pharmacology. - : Wiley-Blackwell Publishing Inc.. - 0306-5251 .- 1365-2125. ; 88:5, s. 2118-2127
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The Cockcroft-Gault (CG) creatinine-based equation is still used to estimate glomerular filtration rate (eGFR) for drug dosage adjustment. Incorrect eGFR may lead to hazardous over- or underdosing METHODS: In a cross-sectional analysis, CG was validated against measured GFR (mGFR) in 14,804 participants and compared with the Modification-of-Diet-in-Renal-Diseases (MDRD), Chronic-Kidney-Disease-Epidemiology (CKD-EPI), Lund-Malmö-Revised (LMR), and European-Kidney-Function-Consortium (EKFC) equations. Validation focused on bias, imprecision, and accuracy (percentage of estimates within ±30% of mGFR, P30), overall and stratified for mGFR, age, and body mass index at mGFR <60 mL/min, as well as classification in mGFR stages.RESULTS: The CG equation performed worse than the other equations, overall and in mGFR, age and BMI subgroups in terms of bias (systematic overestimation), imprecision and accuracy except for patients ≥65 years where bias and P30 were similar to MDRD and CKD-EPI, but worse than LMR and EKFC. In subjects with mGFR<60 mL/min and at BMI [18.5-25[kg/m2 , all equations performed similarly and for BMI<18.5kg/m2 CG and LMR had the best results though all equations had poor P30-accuracy. At BMI≥25kg/m2 the bias of the CG increased with increasing BMI (+17.2mL/min at BMI≥40kg/m2 ). The four more recent equations also classified mGFR stages better than CG.CONCLUSIONS: The CG equation showed poor ability to estimate GFR overall and in analyses stratified for GFR, age, and BMI. CG was inferior to correctly classify the patients in the mGFR staging compared to more recent creatinine-based equations.
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