A randomised, double-blinded, placebo-controlled, parallel study of vitamin D3 supplementation with different schemes based on multiples of 25,000 IU doses

in International Journal of Endocrinology (in press)

Vitamin D (VTD) treatment is recommended in patients presenting different causes of diseases. To treat these patients, physicians rely on the different available pharmaceutical forms present in their ... [more ▼]

Vitamin D (VTD) treatment is recommended in patients presenting different causes of diseases. To treat these patients, physicians rely on the different available pharmaceutical forms present in their country. Unfortunately, even in a given country, there is no consensus on the best way to treat the patients. In Belgium, VTD is mostly prescribed as ampoules containing 25,000 IU of VTD. In this randomised controlled study, we evaluated whether four therapeutic schemes using multiples of 25,000 IU of VTD according to basal vitamin D concentration were able to increase or maintain the 25(OH)D serum level above 30 ng/mL. We randomized 175 subjects who received the drug () or placebo (). Total duration of the study was 12 weeks. Doses ranged from 4167 to 1667 IU/day. Blood sampling was performed at baseline and each 4 visits. In the treated (placebo) subjects, mean 25(OH)D serum concentration was 18.7 (19.1) ng/mL at baseline and 31.5 (20.7) ng/mL at w-12. At the end of the study, 57.1% of the subjects treated with VTD presented 25(OH)D serum concentration ≥30 ng/mL, whereas 94.3% were ≥20 ng/mL. In conclusion, the doses administered were safe and increased or maintained the 25(OH)D concentration ≥20 ng/mL. However, concentrations ≥30 ng/mL were only achieved in 57.1% of the subjects. [less ▲]

Creatinine - or cystatin C - based equations to estimate glomerular filtration in the general population: impact on the epidemiology of chronic kidney disease

in BMC Nephrology (in press)

Chronic kidney disease (CKD) is a major issue in public health. Its prevalence has been calculated using estimation of glomerular filtration rate (GFR) by the creatinine-based equations developed in the ... [more ▼]

Chronic kidney disease (CKD) is a major issue in public health. Its prevalence has been calculated using estimation of glomerular filtration rate (GFR) by the creatinine-based equations developed in the Modified Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) study. Recently, new equations based either on cystatin C (CKD-EPI Cys) or both cystatin and creatinine (CKD-EPI mix) have been proposed by the CKD-EPI consortium. The aim of this study was to measure the difference in the prevalence of stage 3 CKD, defined as an estimated GFR less than 60 mL/min/1.73 m2, in a population using these four equations. METHODS: CKD screening was performed in the Province of Liege, Belgium. On a voluntary basis, people aged over 50 years have been screened. GFR was estimated by the four equations. Stage 3 CKD was defined as a GFR less than 60 mL/min/1.73 m2. RESULTS: The population screened consisted of 4189 people (47% were men, mean age 63 +/- 7y). Their mean serum creatinine and plasma cystatin C levels were 0.88 +/- 0.21 mg/dL and 0.85 +/- 0.17 mg/L, respectively. The prevalence of CKD in this population using the MDRD, the CKD-EPI, the CKD-EPI Cys and the CKD-EPI mix equations was 13%, 9.8%, 4.7% and 5%, respectively. The prevalence of CKD was significantly higher with the creatinine-based (MDRD and the CKD-EPI) equations compared to the new cystatin C-based equations. CONCLUSIONS: Prevalence of CKD varies strongly depending on the method used to estimate GFR. Such discrepancies are of importance and must be confirmed and explained by additional studies, notably by studies using GFR measured with a reference method [less ▲]

Variability of new bone mineral metabolism markers in patients treated with maintenance hemodialysis: implications for clinical decision making

in American Journal of Kidney Diseases (in press)

NGAL biomarqueur de lésion rénale

in Néphrologie & Thérapeutique (in press)

Le diagnostic precoce de l’insufissance renale aigue (IRA) est necessaire et devrait se faire au stade de lesion renale avant meme la degradation du debit de filtration glomerulaire. Plusieurs ... [more ▼]

Le diagnostic precoce de l’insufissance renale aigue (IRA) est necessaire et devrait se faire au stade de lesion renale avant meme la degradation du debit de filtration glomerulaire. Plusieurs biomarqueurs d’atteinte renale aigue sont actuellement a l’etude. Parmi ceux-ci, le Neutrophil Gelatinase Associated Lipocalin (NGAL) semble l’un des plus prometteurs et fait l’objet de nombreuses publications. La performance diagnostique de NGAL, dose dans le plasma ou les urines, pour le depistage de l’IRA depend de nombreux facteurs. Bien que les donnees experimentales recentes soient en faveur de l’utilisation preferentielle du dosage urinaire de NGAL, les donnees cliniques issues de nombreuses etudes ne permettent pas de trancher formellement sur la superiorite du dosage urinaire par rapport au dosage plasmatique pour le depistage des atteintes renales aigues. Il n’en reste pas moins que sur le plan analytique, les techniques de dosage du NGAL urinaire sont actuellement plus fiables que celles du dosage plasmatique. La performance diagnostique de NGAL dans un contexte d’IRA est maximale en chirurgie cardiaque pediatrique. Les resultats, chez l’adulte en postoperatoire de chirurgie cardiaque et dans d’autres situations (reanimation, urgences, transplantation), sont moins convaincants. Par ailleurs, il n’est actuellement pas possible d’extrapoler des etudes cliniques une valeur seuil discriminante unique de NGAL, aussi bien dans les urines que dans le plasma. D’autres etudes sont necessaires pour valider definitivement NGAL comme biomarqueur de l’atteinte renale aigue et en preciser les conditions d’utilisation en pratique clinique. [less ▲]

Comparison between Perkin-Elmer and Chromsytem Vitamin D kit on TQ 5500 from AB SCIEX

(2013, May)

Background: Twenty-five hydroxy-vitamin D (25(OH) D) determination is now routinely prescribed in the Laboratory. Recently, different new methods have been available for this determination. Among them ... [more ▼]

Background: Twenty-five hydroxy-vitamin D (25(OH) D) determination is now routinely prescribed in the Laboratory. Recently, different new methods have been available for this determination. Among them, LCMS/MS methods have emerged in some laboratories. However these methods are generally “home-brewed” and an important variability between them can be seen on different external quality controls, mainly due to a lack of standardization. Recently, Perkin-Elmer (PE) (Turku, Finland) and Chromsystem (CS) (Grafelfing, Germany) launched a standardised method for 25(OH )D determination on LCMS/MS. The aim of our study was to compare these methods on the AB SCIEX TQ5500 (Framingham, Massachusetts, USA) LCMS/MS to measure 25(OH) D3. Methods All the samples were treated according to our preanalyitical procedure: after sampling, they were spun at +4°c at 3500G, aliquoted and kept frozen at -20°c until determination. A method comparison was assessed with CS and PE for the measurement of the 25(OH)D3. We selected 110 remnant samples with 25(OH)D3 levels ranging from 1.6 to 136.7 ng/ml with the PE method to cover the range of usually values Slope and intercept were calculated using Passing and Bablock linear regression and we compared the methods with the Bland and Altman plots. Results For CS, the method is linear up to 250 µg/L, the LOQ is 3.6 µg/L, the intra-assay CV is < 5% and the inter-assay is < 7%. For PE, the method is linear up to 314 µg/L, the LOQ is 3.4 µg/L, the intra-assay CV is < 7.8% and the inter-assay is < 8.5%. On the whole range of measure (n=110), the regression equation is PE = 0.8521+0.9226 (CS) (95%CI of the intercept: (-0.0048;1.37) and 95% CI of the slope (0.89;0.95). The Bland and Altman plot does not show any bias between the two methods (mean difference CS-PE= -2.5 ng/ml) and the standard deviation of the mean is 3,98 ng/ml Conclusion: The performances of these methods are comparable on our new TQ 5500 from AB SCIEX. For now, there is no consensus on a “reference” method for vitamin D quantification. We notice only that the values obtained by CS are systematically a little bit lower than PE’s values, especially for results below 20 ng/ml. However, we have no clear explanation for such behaviour. [less ▲]

Hypovitaminosis D and osteoporosis in burn patients: are the current practices enough ?

in Osteoporosis International (2013), 24(Suppl 1), 377

GFR Estimation Using Standardized Cystatin C in Kidney Transplant Recipients

in American Journal of Kidney Diseases (2013), 61(2), 279-284

Background: The utility of serum cystatin C (SCysC) as a filtration marker in kidney transplantation is uncertain. We took advantage of the recent validation of a reference calibrator for SCysC and of ... [more ▼]

Background: The utility of serum cystatin C (SCysC) as a filtration marker in kidney transplantation is uncertain. We took advantage of the recent validation of a reference calibrator for SCysC and of newly developed CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations (2012) expressed for use with standardized SCysC level to reassess the performance of SCysC as a filtration marker in kidney transplant recipients. Study Design: Study of diagnostic test accuracy. Setting & Participants: 670 kidney transplant recipients from 3 centers undergoing glomerular filtration rate (GFR) measurements from December 2006 to November 2012. Index Test: Estimated GFR (eGFR) using the 2012 SCysC-based and serum creatinine (SCr)/SCysCbased CKD-EPI equations (eGFRcys and eGFRcr-cys, respectively) and the 2009 SCr-based CKD-EPI equation (eGFRcr), with SCysC and SCr measured at a single laboratory between April 2011 and June 2011. Reference Test: Measured GFR (mGFR) using urinary clearance of inulin. Results: Bias (the difference between mGFR and eGFR) was significantly smaller for eGFRcys and eGFRcr-cys versus eGFRcr ( 2.82 and 0.54 vs 4.4 mL/min/1.73 m2, respectively; P 0.001). Precision (standard deviation of the mean bias) also was better for eGFRcys and eGFRcr-cys versus eGFRcr (12 and 11 vs 13 mL/min/1.73 m2 [P 0.001 for both comparisons]). Accuracy (percentage of GFR estimates within 30% of mGFR) was greater for eGFRcys and eGFRcr-cys versus eGFRcr (81% and 86% vs 75%, respectively [P 0.004 and P 0.001]). Net reclassification index with respect to mGFR of 30 mL/min/1.73 m2 for eGFRcr-cys and eGFRcys versus eGFRcr was 18.8% [95% CI, 8.6%-28.9%] and 22.5% [95% CI, 10.2%-34.9%]. Limitations: Patients were exclusively of European descent; association with transplant outcome was not evaluated. Conclusions: Our data validate the use of both the newly developed SCysC-based and SCr/SCysC-based CKD-EPI equations (2012) in kidney transplant recipients. Both equations perform better than the SCr-based CKD-EPI equation (2009). [less ▲]

Ostéomalacie hypophosphatémique hyperphosphaturique avec hypersécrétion de FGF-23

in Lettre du Rhumatologue (La) (2012), 387

Effects of Large-Pore Hemofiltration in a Swine Model of Fulminant Hepatic Failure.

in Artificial Organs (2012), 36(11), 981-987

Among the different potential mechanisms that could lead to brain edema and intracranial hypertension in fulminant hepatic failure (FHF), the inflammatory hypothesis implies that systemic inflammation ... [more ▼]

Among the different potential mechanisms that could lead to brain edema and intracranial hypertension in fulminant hepatic failure (FHF), the inflammatory hypothesis implies that systemic inflammation might be in part responsible for an increase in cerebral blood flow (CBF) and brain water content. In this study, the authors used a validated ischemic FHF swine model to evaluate the effects of 80 kDa large-pore membrane hemofiltration (LPHF) on intracranial pressure (ICP) and CBF, in relation with the clearance of proinflammatory cytokines and blood liver tests, as primary end points. Fifteen pigs were randomized into one of three groups: SHAM, FHF, and FHF + LPHF. All experiments lasted 6 h. In the FHF groups, liver failure was induced by liver ischemia. After 2 h, the FHF + LPHF group underwent 4 h of a zero-balance continuous veno-venous hemofiltration using a 0.7-m(2) , large-pore (78 A) membrane with a cutoff of 80 kDa. ICP, CBF, mean arterial pressure, central venous pressure, and heart rate were continuously monitored and recorded. Arterial aspartate aminotransferase, total bilirubin, creatinine, international normalized ratio, glucose, lactate and serum cytokines interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha were measured at T0, T120, and T360. Over the 6 h following liver ischemia, the FHF group developed a significant increase in ICP. This ICP rise was not observed in the SHAM group and was attenuated in the FHF + LDHF group. However, the ICP levels were not different at T360 in the FHF + LDHF group compared to the FHF group. No significant effect of LPHF on liver tests or levels of proinflammatory cytokines could be demonstrated. In this model, 80 kDa LPHF was not efficient to control FHF intracranial hypertension and to decrease serum cytokine levels. [less ▲]

Demystifying ethnic/sex differences in kidney function: is the difference in (estimating) glomerular filtration rate or in serum creatinine concentration?

in Clinica Chimica Acta (2012), 413(19-20), 1612-17

BACKGROUND: The recent evaluation of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for estimating the glomerular filtration rate (GFR) in multiple ethnicities has raised the ... [more ▼]

BACKGROUND: The recent evaluation of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for estimating the glomerular filtration rate (GFR) in multiple ethnicities has raised the question on how well this equation performs for African-American and Asian subjects. There is no doubt that serum creatinine (Scr) concentration differs between ethnicities and sexes. We show that creatinine-based equations for white populations may be inaccurate for estimating GFR in other ethnic/gender groups, especially in populations from Asia. METHODS: This study presents a mathematical analysis of the CKD-EPI-equation complemented with a literature review of median and reference values for IDMS-standardized Scr-concentrations for multiple ethnicities. RESULTS: The study shows that at equal eGFR-CKD-EPI-values, the ratio of Scr between females and males equals 0.79 and between other ethnicities/sexes and white males is constant too. From this information, it is possible to calculate mean Scr-values that correspond very well with literature values directly obtained from Scr-distributions in healthy white males and females and in black males, but the discrepancy is larger for other populations. CONCLUSIONS: Our results confirm the criticism that has been raised for using the CKD-EPI-equation for these ethnicities. An alternative eGFR-model is proposed based on a population-normalized Scr that needs further validation. [less ▲]