Development and Validation of a Predictive Model of Hypovitaminosis D in General Adult Population: SCOPYD Study.

The worldwide global increase in serum 25-hydroxyvitamin D (25(OH)D) measurements has led some countries to restrict reimbursement for certain clinical situations only. Another approach could consist in providing physicians with screening tools in order to better target blood test prescription. The objective of the SCOPYD study was to identify the best combination of predictors of serum VitD concentration among adults aged 18-70 years. Potential risk factors for VitD deficiency were collected using a comprehensive self-administered questionnaire. A multivariable linear regression was used to build a predictive model of serum 25(OH)D concentration. Among 2488 participants, 1080 (43.4%) had VitD deficiency (<50 nmol/L) and 195 (7.8%) had severe deficiency (<25 nmol/L). The final model included sunlight exposure in the preceding week and during the last holidays, month of blood sampling, age, sex, body mass index, skin phototype, employment, smoking, sport practice, latitude, and VitD supplementation in preceding year. The area under the curve was 0.82 (95% CI (0.78; 0.85)) for severe deficiency. The model predicted severe deficiency with a sensitivity of 77.9% (95% CI (69.1; 85.7)) and a specificity of 68.3% (95% CI (64.8; 71.9)). We identified a set of predictors of severe VitD deficiency that are easy to collect in routine that may help to better target patients for serum 25(OH)D concentration determination.

Distal phalangeal bone erosions observed by HR-pQCT in patients with psoriatic onycholysis.

OBJECTIVES: PsA prevalence among skin psoriasis is ∼30%. Nail psoriasis, especially onycholysis, is present in >70% of PsA and the risk of developing PsA is more than doubled in patients with nail involvement. We hypothesized that onycholysis may be associated with early bone erosions of the DIP joint without harbouring PsA symptoms. METHODS: We compared tendon thickness, assessed by US, and bone erosions, assessed by high-resolution peripheral quantitative CT, of the DIP joint in patients with psoriatic onycholysis without PsA (ONY) with those in patients with cutaneous psoriasis only (PSO). We used patients with PsA as reference (PsA group), and healthy age-matched controls (CTRL). Differences between groups were assessed by analysis of variance tests followed by post hoc analysis using the Scheffe method. RESULTS: Mean (s.e.m.) age of the 87 participants (61% males) was 45.2 (1.3) years. The mean extensor tendon thickness was significantly larger in ONY than in PSO patients. In the PsA group, 68% of patients exhibited erosions of three different shapes: V-, Omega- and U-shape. Association with erosions was greater in the ONY group than in the PSO group (frequency: 57 vs 14%; P < 0.001; mean number of erosions: 1.10 (0.35) vs 0.03 (0.03); P < 0.001). CONCLUSION: Onycholysis was associated with significant enthesopathy and bone erosions in our cohort. These data support the pathogenic role of enthesopathy in PsA. Onycholysis may be considered as a surrogate marker of severity in psoriasis. TRIAL REGISTRATION: ClinicalTrails.gov, https://clinicaltrials.gov, NCT02813720.

Saliva cortisol in relation to aircraft noise exposure: pooled-analysis results from seven European countries.

BACKGROUND: Many studies have demonstrated adverse effects of exposure to aircraft noise on health. Possible biological pathways for these effects include hormonal disturbances. Few studies deal with aircraft noise effects on saliva cortisol in adults, and results are inconsistent. OBJECTIVE: We aimed to assess the effects of aircraft noise exposure on saliva cortisol levels and its variation in people living near airports. METHODS: This study focused on the 1300 residents included in the HYENA and DEBATS cross-sectional studies, with complete information on cortisol sampling. All the participants followed a similar procedure aiming to collect both a morning and an evening saliva cortisol samples. Socioeconomic and lifestyle information were obtained during a face-to-face interview. Outdoor aircraft noise exposure was estimated for each participant's home address. Associations between aircraft noise exposure and cortisol outcomes were investigated a priori for male and female separately, using linear regression models adjusted for relevant confounders. Different approaches were used to characterize cortisol levels, such as morning and evening cortisol concentrations and the absolute and relative variations between morning and evening levels. RESULTS: Statistically significant increases of evening cortisol levels were shown in women with a 10-dB(A) increase in aircraft noise exposure in terms of LAeq, 16h (exp(ß) = 1.08; CI95% = 1.00-1.16), Lden (exp(ß) = 1.09; CI95% = 1.01-1.18), Lnight (exp(ß) = 1.11; CI95% = 1.02-1.20). A statistically significant association was also found in women between a 10-dB(A) increase in terms of Lnight and the absolute variation per hour (exp(ß) = 0.90; CI95% = 0.80-1.00). Statistically significant decreases in relative variation per hour were also evidenced in women, with stronger effects with the Lnight (exp(ß) = 0.89; CI95% = 0.83-0.96) than with other noise indicators. The morning cortisol levels were unchanged whatever noise exposure indicator considered. There was no statistically significant association between aircraft noise exposure and cortisol outcomes in men. CONCLUSIONS: The results of the present study show statistically significant associations between aircraft noise exposure and evening cortisol levels and related flattening in the (absolute and relative) variations per hour in women. Further biological research is needed to deepen knowledge of the pathway between noise exposure and disturbed hormonal regulation, and specially the difference in effects between genders.

Urinary albumin measurement methods.

The quantification of urine albumin is a common practice in Medical Biology laboratories. It allows the assessment of renal injury in common pathologies and many studies have confirmed its role in the diagnosis and prognosis of these disorders. The physicochemical characteristics of albumin in the urine, very different from those in the blood, do not allow the use of the same standardized assay techniques for the blood albumin determination and make it difficult its quantification. Indeed, because of a physiological fragmentation phenomenon, urinary albumin is present in the urine as various small specific peptides. We will present here the main methods of determination of albumin in the urine, which are immuno-turbidimetric and immuno-nephelometric methods, high performance liquid chromatography with steric exclusion and liquid chromatography coupled with mass spectrometry. Currently, immunoanalysis techniques are the most used and are not standardized; large bias can be found between the different kits. This observation calls for a standardization of its determination in the urine.

Hyperphosphatemic tumoral calcinosis caused by FGF23 compound heterozygous mutations: what are the therapeutic options for a better control of phosphatemia?

BACKGROUND: Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare autosomal recessive disease caused by mutations in genes encoding FGF23 or its regulators, and leading to functional deficiency or resistance to fibroblast growth factor 23 (FGF23). Subsequent biochemical features include hyperphosphatemia due to increased renal phosphate reabsorption, and increased or inappropriately normal 1,25-dihydroxyvitamin D (1,25-D) levels. CASE-DIAGNOSIS/TREATMENT: A 15-year-old girl was referred for a 1.2-kg-calcified mass of the thigh, with hyperphosphatemia (2.8 mmol/L); vascular impairment and soft tissue calcifications were already present. DNA sequencing identified compound heterozygous mutations in the FGF23 gene. Management with phosphate dietary restriction, phosphate binders (sevelamer, aluminum, nicotinamide), and acetazolamide moderately decreased serum phosphate levels; oral ketoconazole was secondary administered, leading to significantly decreased 1,25-D levels albeit only moderate additionally decreased phosphate levels. However, therapeutic compliance was questionable. Serum phosphate levels always remained far above the upper normal limit for age. The patient presented with two relapses of the thigh mass, requiring further surgery. CONCLUSIONS: We suggest that control of phosphate metabolism is crucial to prevent recurrences and vascular complications in HFTC; however, the medical management remains challenging.

Teenagers and young adults with nephropathic cystinosis display significant bone disease and cortical impairment.

BACKGROUND: Bone impairment appears to be a novel complication of nephropathic cystinosis despite cysteamine therapy. Its exact underlying pathophysiology is nevertheless unclear. The objective of this study was to evaluate bone status among patients included in the French Crystobs study. METHODS: In addition to clinical data, bone status was evaluated using biomarkers (ALP, PTH, 25-D, 1-25D, FGF23), DXA (spine and total body), and high-resolution peripheral quantitative computed tomography (HR-pQCT) at the tibia and radius. Results were compared to age- and gender-matched healthy controls (1:2 basis) from the local reference cohorts. RESULTS: At a median age of 22.5 (10.2-34.6) years, 10 patients with nephropathic cystinosis were included (2 receiving conservative therapies, 2 undergoing hemodialysis, 6 with a past of renal transplantation); 7 out of 10 patients complained of a bone symptom (past of fracture, bone deformations, and/or bone pain). Biochemicals and spine DXA did not show any significant abnormalities. Using HR-pQCT, significant decreases in cortical parameters (e.g., cortical thickness 850 (520-1100) versus 1225 (480-1680) µm; p < 0.05) and total volumetric bone mineral density (290 (233-360) versus 323 (232-406) mg/cm3; p < 0.05) were observed in cystinotic patients in comparison to controls at the tibia. There were no differences for trabecular parameters. Similar results were observed at the radius. CONCLUSIONS: In this pilot study, bone impairment (rather cortical than trabecular) is a significant clinical problem in nephropathic cystinosis; 70% of patients displayed significant bone symptoms, during teenage or young adulthood. This new complication should be known by physicians because of its potential dramatic impact on quality of life.

Bone, muscle, and metabolic parameters predict survival in patients with synchronous bone metastases from lung cancers.

BACKGROUND: Lung adenocarcinoma regularly induces bone metastases that are responsible for impaired quality of life as well as significant morbidity, including bone pain and fractures. We aimed at identifying whether bone and metabolic biomarkers were associated with the prognosis of lung adenocarcinoma patients with synchronous bone metastases. PATIENTS AND METHODS: POUMOS is a prospective cohort of patients diagnosed with lung adenocarcinoma and synchronous bone metastases. All patients underwent biopsy of bone metastases to confirm diagnosis, including genotyping of oncogenic drivers such as EGFR and KRAS. Whole-body composition was assessed using DEXA scan. Serum levels of C-reactive protein, HbA1C, calcaemia, sCTX, and DKK1 were also measured. RESULTS: Sixty four patients, aged (mean ±â€¯SD) 65 ±â€¯11 years, were included. Thirty-nine (61%) patients had a good performance status (PS 0-1); 56% had >5 bone lesions, and 41% a weight-bearing bone (femour or tibia) involvement. Median overall survival was 7 months. In multivariate analysis, HbA1c (HR = 1.69 [1.10-2.63] per 0.5% decrease; p = .02), DKK1 (HR = 1.28 [1.01-1.61] per 10 ng/mL increase; p = .04), and hypercalcaemia (HR = 2.83 [1.10-7.30]; p = .03) were independently associated with poorer survival. In the subgroup of patients with DEXA, sarcopenia was also associated with poorer survival (HR = 2.96, 95%CI [1.40-6.27]; p = .005). CONCLUSIONS: In patients with lung adenocarcinoma and synchronous bone metastases, bone, sarcopenia, and metabolic parameters were predictors of poor overall survival independently of common prognostic factors. We suggest that, in addition to oncological therapy, supportive treatment dedicated to bone metastases, muscle wasting, and energy metabolism are essential to improve prognosis.

Circulating Klotho Associates With Cardiovascular Morbidity and Mortality During Hemodialysis.

Background: Klotho gene was identified as an aging suppressor. In animals, klotho overexpression extends life span, and defective klotho results in rapid aging and early death. The kidney is the main contributor to circulating klotho levels, and, during chronic kidney disease, renal klotho gene expression is drastically reduced in animals and humans as well. Objective: We aimed to determine the consequences of a serum klotho (seKL) defect on cardiovascular morbidity and mortality during chronic dialysis. Design: The ARNOGENE study was designed to prospectively follow a cohort of hemodialysis patients for 2 years without specific intervention. A total of 769 patients was recruited and followed from the end of 2008 until January 2011. A total of 238 patients was analyzed due to a technical sample conservation issue with other samples. Results: The median seKL was markedly reduced, 360.4 ng/L (interquartile range 176.5) as compared with nondialysis chronic kidney disease patients or healthy volunteers. Patients with a seKL above the first quartile (≥280 ng/L) had a significantly reduced occurrence of outcome combining cardiovascular events and cardiovascular death [odds ratio (OR) = 0.39; 0.19 to 0.78, P = 0.008] compared with patient with klotho <280 ng/L. This effect persisted (OR = 0.86; 0.76 to 0.99, P = 0.03) after adjustment on age, sex, diabetes, cardiac insufficiency, dialysis vintage, and serum hemoglobin, albumin, fibroblast growth factor-23, phosphate, and calcium. Conclusions: These results suggest that, during chronic hemodialysis, conservation of seKL >280 ng/L is associated with a better 2-year cardiovascular protection. Thus, a preserved klotho function supports cardiovascular protection and may represent a prognostic tool and therapeutic target for cardiovascular disease.

Effects of aircraft noise exposure on saliva cortisol near airports in France.

BACKGROUND: Saliva cortisol is a possible marker of noise-induced stress and could then mediate the relation observed between exposure to aircraft or road traffic noise and cardiovascular diseases. However, the association between transportation noise and cortisol levels is still unclear. The objective of the study was to investigate the variability of saliva cortisol concentration as an indicator of disturbed hypothalamus-pituitary-adrenal (HPA) axis regulation in relation to long-term aircraft noise exposure. METHODS: Saliva samples were taken when awakening and before going to bed for 1244 participants older than 18 years of age. Information about health, socioeconomic and lifestyle factors was also collected by means of a face-to-face questionnaire performed at home by an interviewer. Aircraft noise exposure was assessed for each participant's home address using noise maps. Linear regression models were used to evaluate the effects of aircraft noise exposure on the morning and evening cortisol levels and on the daily variation of cortisol per hour. RESULTS: This study suggests a modification of the cortisol circadian rhythm in relation to aircraft noise exposure. This exposure was associated with a smaller variation of cortisol levels over the day, with unchanged morning cortisol levels, but higher cortisol levels in the evening. CONCLUSIONS: These findings provide some support for a psychological stress induced by aircraft noise exposure, resulting in HPA dysregulation and a flattened cortisol rhythm, thus contributing to cardiovascular diseases.

Serum Sclerostin Increases After Acute Physical Activity.

Physical activity has a major impact on bone density and on osteoporosis prevention. Sclerostin is produced by osteocytes and inhibits bone formation. The impact of exercise on sclerostin secretion has not been studied so far. This pilot study aimed to explore circulating sclerostin levels immediately after acute exercise. Healthy young women practicing physical activity less than 120 min per week were enrolled. The exercise was a 45-min, low-speed, treadmill running test. Blood samples were taken at rest before exercise and within 5 min after the end of exercise. We assessed serum creatinine, 25-OH vitamin D, alkaline phosphatase, C-telopeptide of type I collagen, bone-specific alkaline phosphatase, and sclerostin. Sclerostin stability at rest was also validated over the same period of time among women fulfilling the same inclusion criteria. The study included 23 participants (mean ± SD age: 22.9 ± 1.5 years) for the exercise test and 9 participants for the resting test (26.1 ± 3.1 years). There was no difference in body mass index between the two groups. Sclerostin increased after exercise in comparison to baseline (mean ± SEM: 410 ± 27 vs. 290 ± 19 pg/mL; p < 0.001) corresponding to an increase of +44.3 ±5.5%. In the resting test, sclerostin remained stable (303 ± 20 vs. 294 ± 20 pg/mL, p = 0.76). There was a substantial increase in serum sclerostin in untrained healthy young women immediately after physical activity. These results suggest the existence of an acute release of systemic sclerostin in response to physical activity.

Multicenter Evaluation of Cystatin C Measurement after Assay Standardization.

BACKGROUND: Since 2010, a certified reference material ERM-DA471/IFCC has been available for cystatin C (CysC). This study aimed to assess the sources of uncertainty in results for clinical samples measured using standardized assays. METHODS: This evaluation was performed in 2015 and involved 7 clinical laboratories located in France and Belgium. CysC was measured in a panel of 4 serum pools using 8 automated assays and a candidate isotope dilution mass spectrometry reference measurement procedure. Sources of uncertainty (imprecision and bias) were evaluated to calculate the relative expanded combined uncertainty for each CysC assay. Uncertainty was judged against the performance specifications derived from the biological variation model. RESULTS: Only Siemens reagents on the Siemens systems and, to a lesser extent, DiaSys reagents on the Cobas system, provided results that met the minimum performance criterion calculated according to the intraindividual and interindividual biological variations. Although the imprecision was acceptable for almost all assays, an increase in the bias with concentration was observed for Gentian reagents, and unacceptably high biases were observed for Abbott and Roche reagents on their own systems. CONCLUSIONS: This comprehensive picture of the market situation since the release of ERM-DA471/IFCC shows that bias remains the major component of the combined uncertainty because of possible problems associated with the implementation of traceability. Although some manufacturers have clearly improved their calibration protocols relative to ERM-DA471, most of them failed to meet the criteria for acceptable CysC measurements.

Calcium balance in pediatric online hemodiafiltration: Beware of sodium and bicarbonate in the dialysate.

BACKGROUND: Online hemodiafiltration (oHDF) is increasingly used in children; we treated 28 children since 2009, adapting this technique to pediatric patients. METHODS: In this service evaluation audit, we assessed plasma electrolytes to evaluate the evolution of total (tCa) and ionized (iCa) during a session, as well as dialysate calcium (dCa) concentrations. RESULTS: Using a 1.25 mmol Ca/L-dialysate, both tCa and iCa decreased during the session, with iCa falling below 1.1 mmol/L in 4/5 patients. In contrast, using a 1.5 mmol Ca/L-dialysate, iCa remained normal in all patients. Major discrepancies were observed between the expected and the measured dCa: 1.25 vs. 1.01 (0.83-1.04), and 1.5 vs. 1.47 (0.85-1.75) mmol/L, respectively (results presented as median [range]). These differences were explained by the modality of reconstituting dialysate: increasing bicarbonates and/or decreasing sodium requested in the dialysate decreases calcium extraction from the acid preparation. Proof of concept was given when requesting in an "ex-vivo" setting modifications in the requested sodium and bicarbonate in dialysate directly on the Fresenius machine. CONCLUSION: Nephrologists should be aware that "high bicarbonate and/or low sodium" requirements in oHDF decrease calcium in the dialysate.

Enzymatic but not compensated Jaffe methods reach the desirable specifications of NKDEP at normal levels of creatinine. Results of the French multicentric evaluation.

The French Society of Clinical Biochemistry conducted this study to compare the accuracy and performances of the best creatinine enzymatic assays and the compensated Jaffe methods from the same manufacturers. Creatinine was measured in 3 serum pools with creatinine levels of 35.9±0.9 µmol/L, 74.4±1.4 µmol/L, and 97.9±1.7 µmol/L (IDMS determination). The performances of the assays (total error that includes the contribution of bias and imprecision) were evaluated using Monte-Carlo simulations and compared against desirable NKDEP criteria. The enzymatic assays always fell within the desirable total Error of 7.6%. By contrast, this requirement was never obtained for the compensated Jaffe methods at the critical level of 74.4±1.4 µmol/L. Only the compensated Jaffe creatinine on Olympus analyzer reached this specification at 35.9±0.9 and 97.9±1.7 µmol/L levels. This study demonstrates that, despite substantial improvement regarding traceability to the IDMS reference method and precision, compensated Jaffe creatinine methods, by contrast to enzymatic ones, do not reach the desirable specifications of NKDEP at normal levels of creatinine.

The relation between renal function and serum sclerostin in adult patients with CKD.

BACKGROUND AND OBJECTIVES: Sclerostin, a bone antianabolic peptide involved in osteoporosis, is elevated in patients undergoing maintenance dialysis. However, there are no data for patients with early CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Between January and July 2010, serum sclerostin and GFR (calculated by inulin clearance) were measured in 90 patients with CKD. Fasting blood samples were also drawn for determination of calcium, phosphorus, parathyroid hormone, bone alkaline phosphatase, and 25-OH vitamin D. RESULTS: Median GFR was 66.5 (interquartile range, 40.0-88.3) ml/min per 1.73 m(2). Median sclerostin level was 53.5 (interquartile range, 37.5-77.2) pmol/L, was higher in patients with a GFR <60 ml/min per 1.73 m(2), and was highest in those with ESRD. Sclerostin levels were significantly more elevated in men than women (P<0.05). An inverse relationship was found between sclerostin and GFR (r=-0.58; P<0.001), and a positive correlation was seen with age (r=0.34; P<0.01) and serum phosphate (r=0.26; P=0.02). In multiple regression analyses, GFR, sex, and serum phosphate were the only variables associated with serum sclerostin (P<0.001). Age lost its relationship with sclerostin level. CONCLUSIONS: This is the first study reporting higher serum sclerostin levels starting at CKD stage III. GFR, sex, and serum phosphate were the only measures associated with sclerostin level, suggesting that the effect of age reported in the literature might instead be attributable to the altered renal function in the elderly. Correcting the serum phosphorus level may be associated with lower sclerostin levels.

A multicentric evaluation of IDMS-traceable creatinine enzymatic assays.

Chronic kidney disease definition is based on glomerular filtration rate (GFR) estimations which are derived from creatinine-based equations. The accuracy of GFR estimation is thus largely dependent of those of serum creatinine assays. International recommendations highlight the need for traceable creatinine assays. The French Society of Clinical Biochemistry conducted a study for measuring accuracy of creatinine enzymatic methods. This evaluation involved 25 clinical laboratories. Creatinine was measured in serum pools ranging from 35.9±0.9 µmol/L to 174.5±3.1 µmol/L (IDMS determination) using 12 creatinine enzymatic methods. For all creatinine values greater than 74.4±1.4 µmol/L, the bias and imprecision did not exceed 5% and 5.9%, respectively. For the lowest value (35.9±0.9 µmol/L), the bias ranged from -1.8 to 9.9% (with one exception). At this level, the imprecision ranged from 1.9 to 7.8%. The true performances of the assays (couples of bias and relative standard deviation), were evaluated using Monte-Carlo simulations. Most of the assays fall within the maximum Total Error of 12% at all concentrations. This study demonstrates substantial improvements in the calibration, traceability and precision of the enzymatic methods, reaching the NKDEP recommendations. Moreover, most of these assays allowed accurate creatinine measurements for creatinine levels lower than 40 µmol/L.

[Recommendations for the selection and alignment techniques for the determination of creatinine]. / Recommandations pour le choix et l'harmonisation des techniques de dosage de la créatinine.

In 2010, a working group from the French Society of Clinical Chemistry (Société française de biologie clinique - SFBC) and the French Society of Nephrologie (SN) make a proposal to up-date the guidelines for measuring plasma creatinine.

The influence of glomerular filtration rate and age on fibroblast growth factor 23 serum levels in pediatric chronic kidney disease.

BACKGROUND: Fibroblast growth factor 23 (FGF23) is a phosphaturic factor and a suppressor of 1alpha-hydroxylase activity in the kidney. Although its importance in chronic kidney disease (CKD) has been demonstrated in adults, there is little information in pediatric patients. OBJECTIVES: The aims of this study were: 1) to determine reference values for FGF23 serum levels according to glomerular filtration rate (GFR) (measured by the reference standard, inulin clearance), gender, and age; and 2) to evaluate the effects of different etiologies and treatments on FGF23 serum levels in a prospective single-center cohort of 227 CKD children (119 boys). RESULTS: Age, body weight, height, and GFR (mean +/- sd) values were: 11.3 +/- 4.1 yr, 37 +/- 16 kg, 140 +/- 20 cm, and 98 +/- 34 ml/min per 1.73 m(2), respectively. Calcium, phosphate, PTH, 25 hydroxyvitamin D, 1,25 dihydroxyvitamin D, C-terminal FGF23, and intact FGF23 (mean +/- sd) levels were: 2.43 +/- 0.11 mmol/liter, 1.41 +/- 0.22 mmol/liter, 41 +/- 23 pg/ml, 24 +/- 10 ng/ml, 152 +/- 72 pmol/liter, 76 +/- 134 relative units/ml, and 44 +/- 37 pg/ml, respectively. There was a wide range of FGF23 serum levels, but FGF23 levels increased when GFR decreased. FGF23 serum levels were not modified by gender, but they increased with age. In univariate analysis, corticosteroid therapy seemed to be associated with increased FGF23 serum levels. A multivariate linear regression analysis found a significant impact of GFR, body mass index, and solid organ transplantation on FGF23 serum levels. CONCLUSION: Age, GFR, body mass index, and solid organ transplantation seem to influence FGF23 serum levels in a pediatric population. The impact of corticosteroids on FGF23 metabolism should be further investigated; further longitudinal studies will also help to better define the prognostic impact of FGF23 serum levels in pediatric CKD in terms of disease progression, cardiovascular morbidities, and bone disabilities.

The relationship between adipokines, osteocalcin and bone quality in chronic kidney disease.

OBJECTIVES: Osteocalcin, a small peptide secreted by osteoblasts, has been recently described as a circulating hormone involved in the regulation of energy metabolism. In addition, experimental data suggest a regulation of adipocytes by bone, with a stimulation of adiponectin synthesis by osteocalcin and an inverse relationship between serum adiponectin level and bone mineral density (BMD). However, this relationship has not been explored during chronic kidney disease (CKD). METHODS: Osteocalcin, adiponectin and leptin were prospectively measured in a cohort of 61 CKD patients. A new non-invasive 3D bone imaging technique was performed (high-resolution peripheral quantitative computed tomography, HR-pQCT), measuring volumetric BMD (vBMD) and microarchitecture parameters at the distal tibia. RESULTS: Patients' mean age was 67.2 +/- 13.9 years and mean GFR 33 +/- 12 mL/min/1.73 m(2). We found a positive association between serum osteocalcin and adiponectin (r = 0.29, P = 0.021). Univariate analysis showed inverse correlations between serum adiponectin and total vBMD (r = -0.33, P = 0.01), cortical thickness (r = -0.34, P = 0.008) and trabecular vBMD (r = -0.27, P = 0.04). These associations remained significant in multivariate analysis between serum adiponectin and total vBMD, cortical vBMD and cortical thickness. CONCLUSION: We report for the first time an inverse relationship between bone density and adiponectin, as well as a positive association between osteocalcin and adiponectin in CKD II-IV patients.

Impact of standardized calibration on the inter-assay variation of 14 automated assays for the measurement of creatinine in human serum.

PURPOSE: The aim of our study was to measure the inter-assay variation and accuracy of serum creatinine assays and to assess the effect of standardized calibration procedures on this variability. METHODS: We analyzed 30 human sera and three reference materials, using 17 creatinine assays (12 colorimetric, 4 enzymatic and 1 HPLC). We compared two standardized calibration procedures, using either a reference material or secondary standards, to that recommended by the manufacturers. RESULTS: For assays calibrated according to the manufacturers' recommendations, the median inter-assay coefficient of variation (CV) was 14.2% for 20 low samples (45-150 microM), and 7.7% for 10 high samples (250-350 microM). The CV was significantly influenced by the calibration procedure, but none of the standardized calibration procedures significantly improved the inter-assay variability. However, a significant decrease in CV was noted within each type of assay method (colorimetric or enzymatic) when the standardized calibration used standards of level(s) close to the concentrations to be measured. Only the compensated Jaffe technique and the amido-hydrolase assay showed bias of less than 10%. CONCLUSIONS: Standardizing calibration procedures is unlikely to decrease the analytical variability of creatinine assays enough to allow uniform and reliable use of the equations for estimation of glomerular filtration rate.