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See detailCalibration and precision of serum creatinine and plasma cystatin C measurement: impact on the estimation of glomerular filtration rate
DELANAYE, Pierre ULg; CAVALIER, Etienne ULg; Cristol, Jean-Paul et al

in Journal of Nephrology (in press)

Serum creatinine (SCr) is the main variable for estimating glomerular filtration rate (GFR). Due to interassay differences, the prevalence of chronic kidney disease (CKD) varies according to the assay ... [more ▼]

Serum creatinine (SCr) is the main variable for estimating glomerular filtration rate (GFR). Due to interassay differences, the prevalence of chronic kidney disease (CKD) varies according to the assay used, and calibration standardization is necessary. For SCr, isotope dilution mass spectrometry (IDMS) is the gold standard. Systematic differences are observed between Jaffe and enzymatic methods. Manufacturers subtract 0.30 mg/dl from Jaffe results to match enzymatic results (‘compensated Jaffe method’). The analytical performance of enzymatic methods is superior to that of Jaffe methods. In the original Modification of Diet in Renal Disease (MDRD) equation, SCr was measured by a Jaffe Beckman assay, which was later recalibrated. A limitation of this equation was an underestimation of GFR in the high range. The Chronic Kidney Disease Epidemiology (CKD-EPI) consortium proposed an equation using calibrated and IDMS traceable SCr. The gain in performance was due to improving the bias whereas the precision was comparable. The CKD-EPI equation performs better at high GFR levels (GFR[60 ml/ min/1.73 m2). Analytical limitations have led to the recommendation to give a grade ([60 ml/min/1.73 m2) rather than an absolute value with the MDRD equation. By using both enzymatic and calibrated methods, this cutoff-grade could be increased to 90 ml/min/1.73 m2 (with MDRD) and 120 ml/min/1.73 m2 (with CKD-EPI). The superiority of the CKD-EPI equation over MDRD is analytical, but the precision gain is limited. IDMS traceable enzymatic methods have been used in the development of the Lund– Malmo¨ (in CKD populations) and Berlin Initiative Study equations (in the elderly). The analytical errors for cystatin C are grossly comparable to issues found with SCr. Standardization is available since 2011. A reference method for cystatin C is still lacking. Equations based on standardized cystatin C or cystatin C and creatinine have been proposed. The better performance of these equations (especially the combined CKD-EPI equation) has been demonstrated. [less ▲]

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See detailVitamin D status of schoolchildren in Northern Algeria, seasonal variations and determinants of vitamin D deficiency
Djennane, M; Lebbah, S; Roux, C et al

in Osteoporosis International (in press)

Summary There are no published data on the vitamin D status of children living in North Africa. In 435 healthy Algerian children 5–15 years old, we found that vitamin D insufficiency (serum 25 ... [more ▼]

Summary There are no published data on the vitamin D status of children living in North Africa. In 435 healthy Algerian children 5–15 years old, we found that vitamin D insufficiency (serum 25-hydroxyvitamin D (25OHD) <50 nmol/L) was frequent, especially in winter. Low vitamin D status was associated with increased parathyroid hormone (PTH) and leg deformation Introduction As there are no published data on the vitamin D status of children living in North Africa, we evaluated the 25OHD concentration of healthy Algerian children at the end of summer and at the end of winter. As secondary objectives, we studied the various determinants of vitamin D status and the PTH-25OHD relationship in these subjects. Methods Four hundred thirty-five children 5–15 years old were examined and had a blood sample in September 2010. Of them, 408 were sampled again in March 2011. Results Median 25OHD concentration in the whole group was 71.4 nmol/L in September and 52.9 nmol/L in March. In September, 58.4, 29.9, and 8.1 % had a 25OHD concentration below 75, 50, and 30 nmol/L respectively. In March, these percentages increased to 65.2, 41.4, and 17.4 % for the 75, 50, and 30 nmol/L threshold, respectively. In multivariate analysis, older age, darker skin phototype, low daily vitamin D and calcium intake, poor socioeconomic status, and short daily sun exposure remained significantly associated with a 25OHD <50 nmol/L at both visits. In 72 (16.6 %) children, genu varum/valgum was present. Compared to the 363 children without leg deformation, they presented more frequently with the risk factors of vitamin D insufficiency. They also had lower 25OHD concentrations and higher PTH and tALP. Serum PTH and 25OHD concentrations were negatively and significantly correlated (r=−0.43; p<0.001) without a 25OHD threshold above which PTH does not decrease anymore. Conclusion Despite a sunny environment, vitamin D insufficiency is frequent in healthy Algerian children. [less ▲]

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See detailCan we use circulating biomarkers to monitor bone turnover in CKD haemodialysis patients? Hypotheses and facts
DELANAYE, Pierre ULg; Souberbielle, Jean-Claude; Lafage-Proust, Marie-Hélène et al

in Nephrology Dialysis Transplantation (in press)

Assessing bone turnover is a key diagnostic tool in the global management of chronic kidney disease-mineral and bone disorder (CKD-MBD). Since bone biopsy is invasive and cannot be repeated in clinical ... [more ▼]

Assessing bone turnover is a key diagnostic tool in the global management of chronic kidney disease-mineral and bone disorder (CKD-MBD). Since bone biopsy is invasive and cannot be repeated in clinical practice and because bone histomorphometry is less available due to the lack of specialized laboratories, we will focus on potential biomarkers used to assess and monitor bone turnover. After briefly reviewing the pathophysiology of bone turnover in CKD and haemodialysis patients, we will focus on the strengths and limitations of the now recommended biomarkers, i.e. parathormone and bone-specific alkaline phosphatase. We will consider the clinical and also the biological aspects of the topic and also insist on the use of these biomarkers for the monitoring, and the follow-up of the turnover in haemodialysis subjects. Finally, we will discuss some of the most promising, but still not recommended, emerging biomarkers. [less ▲]

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See detailThe Third/Second Generation PTH Assay Ratio as a Marker for Parathyroid Carcinoma: Evaluation Using an Automated Platform
CAVALIER, Etienne ULg; BETEA, Daniela ULg; SCHLECK, Marie-Louise ULg et al

in Journal of Clinical Endocrinology and Metabolism (in press)

Background: Parathyroid carcinoma (PCa) is rare and often difficult to differentiate initially from benign disease. Because PCa oversecretes amino PTH that is detected by third-generation but not by ... [more ▼]

Background: Parathyroid carcinoma (PCa) is rare and often difficult to differentiate initially from benign disease. Because PCa oversecretes amino PTH that is detected by third-generation but not by second-generation PTH assays, the normal generation PTH ( 1) is inverted in PCa (ie, 1). Objective: The objective of the investigation was to study the utility and advantages of automated generation PTH ratio measurements using the Liaison XL platform over existing manual techniques. Setting: The study was conducted at a tertiary-referral academic center. Design: This was a retrospective laboratory study. Subjects: Eleven patients with advanced PCa (mean age 56.0 y). The controls were patients with 1°-hyperparathyroidism (n 144;meanage 53.8 y), renal transplantation (n 41;meanage 50.6 y), hemodialysis (n 80; mean age 65.2 y), and healthy elderly subjects (n 40; mean age 72.6 y). Results: The median (interquartile range) generation PTH ratio was 1.16 (1.10 –1.38) in the PCa group, which was significantly higher than the control groups: 0.74 (hemodialysis, 0.71–0.75), 0.77 (renal transplant, 0.73–0.79), 0.80 (healthy elderly, 0.74–0.83), and 0.76 (1°-hyperparathyroidism, 0.74–0.78). An inverted -generation PTH ratio ( 1) was seen in 9 of 11 PCa patients (81.8%) and in 7 of 305 controls (2.3%), 3 of 80 hemodialysis (3.8%), and 4 of 144 1°-hyperparathyroidism patients (2.8%). Of four PCa patients who had a normal PTH ratio with the manual method, two had an inverted -generation PTH ratio with the automated method. Conclusions: Study of the -generation PTH ratio in large patient populations should be feasible using a mainstream automated platform like the Liaison XL. The current study confirms the utility of the inverted -generation PTH ratio as a marker of PCa (sensitivity: 81.8%; specificity: 97.3%). [less ▲]

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See detailA Double-Blind, Placebo Controlled, Randomized Trial to Assess the Impact of a Monthly Administration of 50,000 IU of Vitamin D3 for 6 Months on Serum Levels of 25-Hydroxyvitamin D in Healthy Young Adults
Brunel, Elodie ULg; SCHNITZLER, Maryline ULg; Foidart-Dessalle, Marguerite ULg et al

in International Journal of Endocrinology (in press)

In this double blind, unicentre, randomized, placebo controlled study, we evaluated the changes in 25-hydroxyvitamin D (25(OH)D) serum levels in 150 young Belgian adults (18–30 years), monthly ... [more ▼]

In this double blind, unicentre, randomized, placebo controlled study, we evaluated the changes in 25-hydroxyvitamin D (25(OH)D) serum levels in 150 young Belgian adults (18–30 years), monthly supplemented with 50,000 IU of vitamin D (VTD) or placebo for 6 months, from November 2010 to May 2011. At T0, 30% of the population presented 25(OH)D serum levels below 20 ng/mL. In the VTD-treated group, mean serum levels increased from 21.2 ± 8.2 to 30.6 ± 8.8 ng/mL (𝑃 < 0.001) at T3mo and to 36.0 ± 9.2 ng/mL (𝑃 < 0.001) at T6mo. Despite documented VTD intake, no changes in serum levels were, however, observed in 10% of the treated group. In the placebo group, mean 25(OH)D serum levels decreased from22.8 ± 8.5 to 14.0 ± 6.9 ng/mL at T3mo (𝑃 < 0.001) but returned to values not significantly different from those observed at T0 (23.5 ± 8.6 ng/mL) at T6mo. No difference between serum calcium levels was observed between the groups throughout the study. In conclusion, monthly supplementation with50,000UIofVTDinwinter canwarrant serum25(OH)Dlevels above 20ng/mL in96.2%of thosehealthy young adultswithout inducing unacceptably high 25(OH)D concentration. This supplementation is safe andmay be proposed without 25(OH)D testing. [less ▲]

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See detailAt which level of vitamin D should we aim?
CAVALIER, Etienne ULg

Conference (2014, January 18)

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See detailDetection of decreased glomerular filtration rate in intensive care units: serum cystatin C versus serum creatinine
DELANAYE, Pierre ULg; CAVALIER, Etienne ULg; Morel, Jérôme et al

in BMC Nephrology (2014), 15(9), 1471-2369

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See detailEnzymatic creatinine assays allowestimation of glomerular filtration rate in stages 1 and 2 chronic kidney disease using CKD-EPI equation
Kuster, Nils; Cristol, Jean-Paul; CAVALIER, Etienne ULg et al

in Clinica Chimica Acta (2014), 428

The National Kidney Disease Education Program group demonstrated that MDRD equation is sensitive to creatinine measurement error, particularly at higher glomerular filtration rates. Thus, MDRD-based eGFR ... [more ▼]

The National Kidney Disease Education Program group demonstrated that MDRD equation is sensitive to creatinine measurement error, particularly at higher glomerular filtration rates. Thus, MDRD-based eGFR above 60 mL/min/1.73 m2 should not be reported numerically. However, little is known about the impact of analytical error on CKD-EPI-based estimates. This study aimed at assessing the impact of analytical characteristics (bias and imprecision) of 12 enzymatic and 4 compensated Jaffe previously characterized creatinine assays on MDRD and CKD-EPI eGFR. In a simulation study, the impact of analytical error was assessed on a hospital population of 24 084 patients. Ability using each assay to correctly classify patients according to chronic kidney disease (CKD) stages was evaluated. For eGFR between 60 and 90 mL/min/1.73 m2, both equations were sensitive to analytical error. Compensated Jaffe assays displayed high bias in this range and led to poorer sensitivity/specificity for classification according to CKD stages than enzymatic assays. As compared to MDRD equation, CKD-EPI equation decreases impact of analytical error in creatinine measurement above 90 mL/min/1.73 m2. Compensated Jaffe creatinine assays lead to important errors in eGFR and should be avoided. Accurate enzymatic assays allow estimation of eGFR until 90 mL/min/1.73 m2 with MDRD and 120 mL/min/1.73 m2 with CKD-EPI equation. [less ▲]

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See detailComprehensive plasma profiling for the characterization of graft-versus-host disease biomarkers
De Bock, Muriel; BEGUIN, Yves ULg; Leprince, Pierre ULg et al

in Talanta (2014), 125

Acutegraft-versus-hostdisease(aGVHD)remainsalife-threateningcomplicationofhematopoieticstem cell transplantation(HSCT)thereforelimitingitsapplication.TooptimizethemanagementofaGVHDand reduce therapy ... [more ▼]

Acutegraft-versus-hostdisease(aGVHD)remainsalife-threateningcomplicationofhematopoieticstem cell transplantation(HSCT)thereforelimitingitsapplication.TooptimizethemanagementofaGVHDand reduce therapy-relatedtoxicity,earlyspecific markersareneeded.Themainobjectiveofthisstudywas to uncoverdiagnosticbiomarkersbycomparingplasmaproteinprofiles ofpatientsatthetimeofacute GVHDdiagnosiswiththoseofpatientsundergoingHSCTwithoutaGVHD.Additionalanalysisofsamples taken 15daysbeforeaGVHDdiagnosiswasalsoperformedtoevaluatethepotentialofournewly discoveredbiomarkersforearlydiagnosis.Togetcomplementaryinformationfromplasmasamples, we usedthreedifferentproteomicapproaches,namely2D-DIGE,SELDI-TOF-MSand2D-LC-MSE. Weidentified andconfirmed bythemeansofindependenttechniques,thedifferentialexpression of severalproteinsindicatingsignificantly increasedinflammation responseanddisturbanceinthe coagulation cascade.Thevariationoftheseproteinswasalreadyobserved15daysbeforeGVHD diagnosis, suggestingthepotentialearlydetectionofthediseasebeforesymptomsappearance. Finally,logisticregressionanalysisdeterminedacompositebiomarkerpanelcomprising fibrinogen, fragment of fibrinogenbetachain,SAA,prothrombinfragments,apolipoproteinA1andhepcidinthat optimallydiscriminatedpatientswithandwithoutGVHD.Theareaunderthereceiveroperating characteristiccurvedistinguishingthese2groupswas0.95. [less ▲]

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See detailPrevalence of vitamin D inadequacy in european women aged over 80 years
Bruyère, Olivier ULg; Slomian, Justine ULg; Beaudart, Charlotte ULg et al

in Osteoporosis International (2014), 25(2), 196

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See detailLa vitamine D, état des lieux et recommandations
CAVALIER, Etienne ULg

Conference (2013, November 16)

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See detailPINP in renal impaired patients: the assay matters
CAVALIER, Etienne ULg; DELANAYE, Pierre ULg

Poster (2013, November 08)

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See detailModification of diet in renal disease versus chronic kidney disease epidemiology collaboration equation to estimate glomerular filtration rate in obese patients
BOUQUEGNEAU, Antoine ULg; Vidal-Petiot, Emanuelle; Vrtovsnik, François et al

in Nephrology Dialysis Transplantation (2013), 28(4), 122-130

Background Obesity is a recognized risk factor for both the development and progression of chronic kidney disease (CKD). Accurate estimation of glomerular filtration rate (GFR) is thus important in these ... [more ▼]

Background Obesity is a recognized risk factor for both the development and progression of chronic kidney disease (CKD). Accurate estimation of glomerular filtration rate (GFR) is thus important in these patients. We tested the performances of two creatinine-based GFR estimates, the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, in an obese population. Methods Patients with body mass index (BMI) > 30 kg/m2 were included. The reference method for measured GFR (mGFR) was 51Cr-EDTA (single-injection method, two blood samples at 120 and 240 min). Both indexed and non-indexed results were considered. Serum creatinine was measured using the IDMS-traceable compensated Jaffe method. Mean bias (eGFR–mGFR), precision (SD around the bias) and accuracy within 30% (percentage of estimations within 30% of mGFR) were calculated for both equations. Results The population included 366 patients (185 women) from two different areas. Mean age was 55 ± 14 years, and mean BMI was 36 ± 7 kg/m2. Mean mGFR was 56 ± 26 mL/min/1.73 m2 (71 ± 35 mL/min without indexation). In the total population, mean bias was +1.9 ± 14.3 and +4.6 ± 14.7 mL/min/1.73 m2 (P < 0.05), and accuracy 30% was 80 and 76% for the MDRD and CKD-EPI equations (P < 0.05), respectively. In patients with mGFR > 60 mL/min/1.73 m2, mean bias was +4.6 ± 18.4 and +9.3 ± 17.2 mL/min/1.73 m2 (P < 0.05), and accuracy 30% was 81 and 79% (NS) for the MDRD and CKD-EPI equations, respectively. Conclusions The CKD-EPI equation did not outperform the MDRD study equation in this population of obese patients [less ▲]

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