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Age-related cognitive decline arises from alterations in brain structure as well as in sleep-wake regulation. Here, we investigated whether preserved wake-dependent regulation of cortical function could represent a positive factor for cognitive fitness in aging. We quantified cortical excitability dynamics during prolonged wakefulness as a sensitive marker of age-related alteration in sleep-wake regulation in 60 healthy older individuals (50-69 y; 42 women). Brain structural integrity was assessed with amyloid-beta- and tau-PET, and with MRI. Participants' cognition was investigated using an extensive neuropsychological task battery. We show that individuals with preserved wake-dependent cortical excitability dynamics exhibit better cognitive performance, particularly in the executive domain which is essential to successful cognitive aging. Critically, this association remained significant after accounting for brain structural integrity measures. Preserved dynamics of basic brain function during wakefulness could therefore be essential to cognitive fitness in aging, independently from age-related brain structural modifications that can ultimately lead to dementia.

The aim of this study was to describe the effects of a 64.2 km ultra-trail on the biomarkers of muscle damage, inflammation and oxidative stress, and compare the results observed with an ECG and an echocardiogram, both performed before and after the race.Thirty-three ultra-trail volunteers (45.8 ± 8.7 years old) were enrolled in our study. Three blood tests were drawn from each runner, one just before (TPRE), one just after (TPOST) and the last 3 h after the end of the race (TPOST3h).All the markers increased. The maximum concentrations observed were at TPOST3h and were significant (p < 0.001) for creatine kinase, creatine kinase isoform MB, high-sensitivity C-reactive protein, uric acid and for the ratio of reduced glutathione to oxidised glutathione. However, in the case of myoglobin, high-sensitive troponin T, N-terminal pro-brain natriuretic peptide, oxidised glutathione, myeloperoxidase, cystatin C and creatinine, the most significant increases were at TPOST (p < 0.001). Modifications were observed in the medical imaging using echocardiography such as reduction of left ventricule end-sytolic and diastolic volumes and left ventricular global longitudinal strain. ECG showed electrical criteria for left ventricular hypertrophy and incomplete right bundle branch block after the race.Endurance races cause significant physiological stress to the body that can be measured by the increase of different biomarkers. From a laboratory perspective, it is important to take into account the possible exercise performed previous to the testing to avoid a misinterpretation of the results. From a training perspective, due to these increases in biomarkers, it is recommended that runners wait at least 72 h after an ultra-trail before subsequent training. In addition a transient impairment of ventricular function due to dehydration were observed.

Biomarkers are well established for the diagnosis of myocardial infarction, heart failure and cardiac fibrosis. Different papers on cardiac biomarker evolution during exercise have been published in the literature and generally show mild to moderate elevations. However, the mechanism responsible for these elevations, reflecting physiological or even pathophysiological changes, still has to be clearly elucidated. There are also indications of higher cardiac risk in poorly trained athletes than in well-trained athletes. Whether regular repetition of intensive exercise might lead, in the longer term, to fibrosis and heart failure remains to be determined. In this review, we summarized the main research about the effects of intense exercise (in particular, running) on cardiac biomarkers (including troponins, natriuretic peptides, etc.). We found that cardiac fibrosis biomarkers seemed to be the most informative regarding the biological impact of intense physical activity.

Urine samples can be readily obtained from patients in everyday clinical practice. Therefore, the availability of urine allows physicians to obtain relevant clinical information in a timely manner. Since the measurement of urinary protein levels is essential in diagnosing and treating a host of diseases, the potential detection of urinary proteins by urinary strips in an easy, quick, and cheap way is very attractive. However, to ensure optimal use of urinary strips, one needs to be aware of their characteristics and their limitations. In this review, we discuss the characteristics of the urinary strips available for testing urinary protein levels and for detecting urinary albumin. We then consider their analytical performances in their most widely used clinical applications (e.g., in pregnancy, chronic kidney disease, diabetes, and screening of the general population).

Sclerostin is sometimes presented as a promising biomarker in assessing bone health both in the general population and chronic kidney disease patients. However, it is still unclear whether it has any true added value compared to existing bone biomarkers in predicting bone turnover and/or bone density in chronic kidney disease patients. A wealth of papers has been published to evaluate the association between sclerostin and vascular calcifications development or even as prognostic biomarker for mortality, but often with conflicting results. Standardization and harmonization of analytical techniques is a prerequisite to advance clinical knowledge in sclerostin.

Historically, the determination of low concentration analytes was initially made possible by the development of rapid and easy-to-perform immunoassays (IAs). Unfortunately, typical problems inherent to IA technologies rapidly appeared (e.g. elevated cost, cross-reactivity, lot-to-lot variability, etc.). In turn, liquid chromatography tandem mass spectrometry (LC-MS/MS) methods are sensitive and specific enough for such analyses. Therefore, they would seem to be the most promising candidates to replace IAs. There are two main choices when implementing a new LC-MS/MS method in a clinical laboratory: (1) Developing an in-house method or (2) purchasing ready-to-use kits. In this paper, we discuss some of the respective advantages, disadvantages and mandatory requirements of each choice. Additionally, we also share our experiences when developing an in-house method for cortisol determination and the implementation of an “ready-to-use” (RTU) kit for steroids analysis.

Increased cardiovascular morbidity and mortality in chronic kidney disease (CKD) represents an emerging major health problem. Indeed, disturbances in mineral and bone metabolism occur frequently in CKD and are termed chronic kidney disease - mineral and bone disorder (CKD-MBD). These can lead to cardiovascular pathology, resulting in an increased cardiovascular risk. Bone alkaline phosphatase (BALP) is essential for biomineralization. Recent findings demonstrate a crucial role for BALP in the pathogenesis of vascular calcification and identified it as a promising predictor of mortality in CKD. In conjunction with parathyroid hormone (PTH), serum BALP has been suggested as a biomarker of bone turnover in CKD-MBD. In contrast to PTH, serum BALP demonstrates a lower variability and may thus be better suited for the diagnosis and longitudinal follow-up of bone turnover. The linear association with mortality, compared to the U-shaped curve for PTH, is an additional advantage, making BALP more suitable than PTH as a treatment target in CKD. Here we review the main characteristics of alkaline phosphatase isozymes/isoforms and the various assays currently used in clinical routine laboratories. We also discuss the role of BALP in both physiological and pathological mineralization, and the clinical benefit of BALP determination in CKD.

It has been more than 80 years since the discovery of vitamin D and its ability to cure rickets in children. Vitamin D is a secosteroid and comes in two distinct forms, vitamin D2 and vitamin D3. During the last 40 years, the synthesis and metabolism of vitamin D were elucidated and more than 50 metabolites of vitamin D have been discovered, though commercial measurement procedures have been developed for only a few of them. The clinical significance of vitamin D in calcium and phosphorus homeostasis is well appreciated. However, recent epidemiological data have indicated that it has several extra-skeletal physiologic actions which are still a matter of scientific debate. Both research findings and the debate around the interpretation of the research results have created increased interest in more measurements of vitamin D. With the ever growing family of measurable vitamin D metabolites and the measuring techniques comes a question: What metabolic product will provide the right answers and which is the best way to measure it. The right choice of analytical technique is connected with the question of which metabolite we aim to measure, what is its serum concentration, and the purpose of the measurement. The aim of the first part of this review is to provide a brief overview of vitamin D metabolism and a more detailed analysis of the existing methods and the status of standardization for the measurement of 25-hydroxyvitamin D.

PURPOSE OF REVIEW The review critically appraises the most recent and important meta-analyses that have assessed the effect of vitamin D supplementation on bone health in the older population. RECENT FINDINGS Vitamin D status is generally lower in study participants with bone wasting. However, studies on the effects of vitamin D supplementation on bone health, summarized in different meta-analyses, have provided conflicting results, likely because of the heterogeneity between studies. Interventional studies performed using more physiological doses of vitamin D (i.e. avoiding very large, nonphysiological doses) or in study participants with low vitamin D status have provided more beneficial effects on bone health. SUMMARY Meta-analyses assessing the impact of vitamin D in the treatment of osteoporosis are heterogeneous in their conception or their results and sometimes have included inappropriate studies to answer the useful research question for the clinician, making the interpretation and the clinical use of these conflicting meta-analyses quite difficult.

International audience; With intermittent vitamin D supplementation, serum 25-hydroxyvitamin D (25OHD) levels may remain stable only if the dosing interval is shorter than 3 months, the ideal perhaps being about 1 month. Recent data support moderate daily vitamin D doses instead of high intermittent doses, notably in elderly patients prone to falls. The level of evidence is low, however, with no head-to-head comparisons of clinical outcomes such as fractures and falls in groups given identical dosages daily versus intermittently. A challenge to daily vitamin D supplementation in France is the absence of a suitable pharmaceutical formulation. In addition, daily dosing carries a high risk of poor adherence. Until suitable vitamin D3 formulations such as tablets or soft capsules each containing 1000 or 1500 IU become available, we suggest intermittent supplementation according to 2011 GRIO guidelines. Among the available dosages, the lowest should be preferred, with the shortest possible interval, e.g., 50,000 IU monthly rather than 100,000 every two months.

Context Hypophosphatemic rickets (HR) is a group of rare hereditary renal phosphate wasting disorders caused by mutations in PHEX, FGF23, DMP1, ENPP1, CLCN5, SLC9A3R1, SLC34A1, or SLC34A3. Objective A large kindred with 5 HR patients was recruited with dominant inheritance. The study was undertaken to investigate underlying genetic defects in HR patients. Design Patients and their family members were initially analyzed for PHEX and FGF23 mutations using polymerase chain reaction sequencing and copy number analysis. Exome sequencing was subsequently performed to identify novel candidate genes. Results PHEX and FGF23 mutations were not detected in the patients. No copy number variation was observed in the genome using CytoScan HD array analysis. Mutations in DMP1, ENPP1, CLCN5, SLC9A3R1, SLC34A1, or SLC34A3 were also not found by exome sequencing. A novel c.979–96 T>A mutation in the SGK3 gene was found to be strictly segregated in a heterozygous pattern in patients and was not present in normal family members. The mutation is located 1 bp downstream of a highly conserved adenosine branch point, resulted in exon 13 skipping and in-frame deletion of 29 amino acids, which is part of the protein kinase domain and contains a Thr-320 phosphorylation site that is required for its activation. Protein tertiary structure modelling showed significant structural change in the protein kinase domain following the deletion. Conclusions The c.979–96 T>A splice mutation in the SGK3 gene causes exon 13 skipping and deletion of 29 amino acids in the protein kinase domain. The SGK3 mutation may cause autosomal dominant HR.

Background Simultaneous measurement of 25(OH)D and 24,25(OH)2D is a new tool for predicting vitamin D deficiency and allows evaluating CYP24A1 lack of function. Interpretation of 24,25(OH)2D should be performed according to 25(OH)D levels and a ratio, called the vitamin D metabolite ratio (VMR) has been proposed for such a purpose. Unfortunately, the VMR can be expressed in different ways and cannot be used if 24,25(OH)2D concentrations are undetectable. Here, we propose evaluating the enzyme activity taking into consideration the probability that a normal population presents undetectable 24,25(OH)2D concentrations according to 25(OH)D levels. We thus retrospectively measured 25(OH)D and 24,25(OH)2D in a population of 1200 young subjects to evaluate the 25(OH)D threshold above which the enzyme was induced. Methods Serum samples from 1200 infants, children, adolescent and young adults were used to simultaneously quantify 25(OH)D and 24,25(OH)2D by LCMS/MS. Results Median (interquartile range [IQR]) levels were 20.6 (14.4–27.2) ng/mL for 25(OH)D. 172 subjects (14.3%) presented 24,25(OH)2D values below the LOQ. When 25(OH)D values were 21 ng/mL. Conclusions We suggest using a statistical approach to evaluate CYP24A1 function according to 25(OH)D concentrations. Our results also show that vitamin D deficiency, as defined biochemically, could be around 20 ng/mL in infants, children, adolescent and young adults and that vitamin D deficiency could be evaluated on a more individual basis.

Introduction Determination of creatinine and estimation of Glomerular Filtration Rate (GFR) rapidly before injection of contrast media provides early detection of high-risk patients for acute kidney failure. Hence, a rapid point-of-care (POC) device (result in 30 s) allowing creatinine measurement and eGFR could be of interest. To validate this method, we considered a population referred for measuring GFR. Methods Iohexol plasma clearance was used to measure GFR. For each subject, enzymatic creatinine was quantified with two different devices: in plasma with the Roche Cobas analyzer and in capillary blood with the Nova Biomedical POC device. Both values of creatinine were used in the CKD-EPI equation for estimated glomerular filtration rate (eGFR). eGFR using POC was compared to eGFR using Cobas and to mGFR by Passing Bablok regression, calculation of bias, precision and accuracy (or concordance) within 30%. Also, we calculated the rate of discrepant staging (eGFR >60 or ≤ 60 when mGFR is actually ≤60 and > 60) with both creatinine methods. Results 120 subjects (52 ± 13 years, 49% of women) were included. Mean mGFR was 77 ± 27 mL/min/1.73m2 with 29 patients presenting mGFR 60 mL/min/1.73m2 whereas mGFR it was ≤60 and 10% (9.2%) of them would have been considered with GFR ≤60 mL/min/1.73m2 when mGFR was >60. Conclusion Creatinine measured with the POC has an acceptable performance when used with the CKD-EPI equation to estimate GFR. Its ability to detect GFR

Background Previous studies have suggested that exercising may induce cardiac damage. Galectin-3 (Gal-3) and soluble suppression of tumorigenicity 2 (ST2) are very interesting biomarkers for heart failure and myocardial fibrosis. We aimed to compare the kinetics of emerging fibrosis cardiac biomarkers as Gal-3 and ST-2 in endurance runners, and recreational runners before and after a running event represented by a marathon and an ultratrail event. Methods Blood samples were taken from 19 healthy non-elite marathon runners (42 km), 27 ultratour runners (67 km), and 14 recreational runners who represented the control group (10 km) just before the run (T0), just after (T1) and 3 h after (T2), in order to analyze Gal-3, ST2, hsTnT, NT-proBNP, CKMB and hsCRP. We compared the percentage of evolution and the slopes obtained from T0 to T1 (pT0T1) and from T1 to T2 (pT1T2), between the different groups of runners participating in three different races. Results Plasma cardiac biomarker concentrations increased significantly from baseline to immediately post-exercise and most of the time decreased over the subsequent 3-h period. For pT0T1 and pT1T2, the markers Gal-3 and ST2 showed a significant difference between types of run (p Conclusions Gal-3 and ST2 are considered as a reflection of cardiac fibrosis and remodeling. The evolution of both was different, particularly after the recovery time. ST2 values exceeding cutoff values at any time.

Background Parathyroid hormone (PTH) measurement is important for patients with disorders of calcium metabolism, including those needing bone-turnover monitoring due to chronic kidney disease–mineral bone disorder. There are currently 2 generations of PTH immunoassays on the market, both having cross-reactivity issues and lacking standardization. Therefore, we developed an LC-MS/MS higher-order method for PTH analysis. Methods The method was calibrated against the international standard for 1-84 PTH (WHO 95/646). Antibody-free sample preparation with the addition of an isotope-labeled internal standard was performed by solid-phase extraction. Extracts were analyzed by LC-MS/MS. EDTA-K2 plasma was used throughout the development and validation. Bias and uncertainty sources were tested according to ISO 15193. Clinical Laboratory Standards Institute guidelines and reference measurement procedures were consulted for the design of the validation. Patient samples and external quality controls were compared between LC-MS/MS and 2 third-generation immunoassays. Results The method was validated for 1-84 PTH from 5.7 to 872.6 pg/mL. The interassay imprecision was between 1.2% and 3.9%, and the accuracy ranged from 96.2% to 103.2%. The measurement uncertainty was Conclusions This LC-MS/MS method, which is independent of antibodies, is suitable for a wide range of PTH concentrations. The obtained analytical performance specifications demonstrate that development of a reference measurement procedure will be possible once a higher order reference standard is available.

Bone turnover markers (BTMs) are released during the bone remodelling cycle and are measurable in blood or urine, reflecting bone remodelling rate. They have been useful in elucidating the pharmacodynamics and effectiveness of osteoporosis medication in clinical trials and are increasingly used in routine clinical management of osteoporosis, especially for monitoring therapy, in addition to their use in other metabolic bone disease such as Paget's disease of bone and osteomalacia. Serum β isomerised C-terminal telopeptide of type I collagen and pro-collagen I N-terminal propeptide have been designated as reference BTMs for use in osteoporosis. In addition, bone-specific isoenzyme of alkaline phosphatase (B-ALP) secreted by osteoblasts and tartrate-resistant acid phosphatase 5b (TRACP-5b) secreted by osteoclasts are also found to be specific markers of bone formation and resorption, respectively. The concentrations of the latter enzymes in blood measured by immunoassay provide reliable measures of bone turnover even in the presence of renal failure. B-ALP is recommended for use in the assessment of renal bone disease of chronic kidney disease, and TRACP-5b shows promise as a marker of bone resorption in that condition. BTMs in blood do not suffer from biological variation to the same extent as the older BTMs that were measured in urine. Appropriate patient preparation and sample handling are important in obtaining accurate measures of BTMs for clinical use. Reference change values and treatment targets have been determined for the reference BTMs for their use in monitoring osteoporosis treatment. Further ongoing studies will enhance their clinical applications.

Tartrate-resistant acid phosphatase, isoform 5b (TRACP-5b) is a bone resorption marker not influenced by renal function or food intake. TRACP-5b can be measured with Nittobo Medical enzymatic-immunoassay and IDS-iSYS automated immunoassay. We evaluated the Nittobo assay and established reference ranges for a Western-European population. We compared Nittobo and IDS results in different well-defined clinical populations.We established the limits of detection and quantification (LOD-LOQ), linearity, imprecision and the reference ranges in 119 males, 50 women (45 years) and 120 women (60 years) for TRACP-5b with the Nittobo assay. We compared both assays in 30 hemodialyzed (HD), and 40 stage 3-5 patients suffering from chronic kidney disease (CKD), 40 patients suffering from rheumatoid arthritis and osteoporosis and 80 post-menopausal women. We measured TRACP-5b, β-crosslaps (β-CTX), bone alkaline phosphatase (B-ALP) and PTH in 20 hemodialyzed (HD) and 40 CKD patients.LOD and LOQ were 0.02 and 0.35 U/L. CV ranged from 8.3 to 4.3% (2/5 samples presenting CV desirable CV). Method was linear up to of 11.3 U/L. Upper and lower limits of normality were 0.8-7.6 U/L in men, 0.9-4.7 U/L in women45 and 0.9-7.1 U/L in women60. The regression equation between the 2 methods was Nittobo = 1.13 (95% CI: 1.09-1.16) × iSYS - 0.4 (95% CI: -0.5; -0.3). TRACP-5b and b-ALP were in their respective reference ranges for most of CKD and HD patients. That was not the case for β-CTX, which increased with decreasing eGFR.Nittobo TRACP-5b presents interesting analytical features and a good concordance with IDS iSYS. These methods could thus potentially be harmonized.

RATIONALE & OBJECTIVE: Bone biopsy remains the gold standard for diagnosing renal osteodystrophy as comparable noninvasive alternatives have yet to be established. This study investigated the diagnostic accuracy of biochemical markers of skeletal remodeling to predict bone turnover. STUDY DESIGN: Cross-sectional retrospective diagnostic test study. SETTING & PARTICIPANTS: Patients with chronic kidney disease glomerular filtration rate categories 4-5, including patients treated with dialysis (G4-G5D) and kidney transplant recipients with successful transiliac bone biopsies. TESTS COMPARED: Bone turnover as determined by bone histomorphometry was compared with the following biochemical markers: full-length (amino acids 1-84) "biointact" parathyroid hormone (PTH), bone-specific alkaline phosphatase (BsAP), intact procollagen type I N-terminal propeptide (PINP), and tartrate-resistant acid phosphatase isoform 5b (TRAP5b). OUTCOME: Diagnostic performance was evaluated by area under the receiver operator characteristics curve (AUC), sensitivity, specificity, and negative and positive predictive values. Optimal diagnostic cutoffs were determined in an exploration cohort (n = 100) and validated in a separate cohort (n = 99). RESULTS: All biomarkers differed across categories of low 33 (17%), normal 109 (55%), and high 57 (29%) bone turnover. AUC values were in the range of 0.75-0.85. High negative predictive values (≥90%) were found for both high and low bone turnover, indicating the ability to rule out both conditions using the suggested biomarker cutoffs. The highest diagnostic performances were seen with combinations of biomarkers, with overall diagnostic accuracies of 90% for high turnover, and 78% for low turnover. Results were comparable for kidney transplant candidates and recipients in a sensitivity analysis. LIMITATIONS: The single-center approach and heterogeneity of the study cohort are main limitations of this study. CONCLUSIONS: We conclude that the diagnostic performance of biochemical markers of bone turnover is acceptable, with clinical utility in ruling out both high and low turnover bone disease. ispartof: AMERICAN JOURNAL OF KIDNEY DISEASES vol:79 issue:5 pages:667-+ ispartof: location:United States status: published

Background Coronavirus disease COVID-19 has become a public health emergency of international concern. Together with the quest for an effective treatment, the question of the post-infectious evolution of affected patients in healing process remains uncertain. Krebs von den Lungen 6 (KL-6) is a high molecular weight mucin-like glycoprotein produced by type II pneumocytes and bronchial epithelial cells. Its production is raised during epithelial lesions and cellular regeneration. In COVID-19 infection, KL-6 serum levels could therefore be of interest for diagnosis, prognosis and therapeutic response evaluation. Materials and methods Our study retrospectively compared KL-6 levels between a cohort of 83 COVID-19 infected patients and two other groups: healthy subjects (n = 70) on one hand, and a heterogenous group of patients suffering from interstitial lung diseases (n = 31; composed of 16 IPF, 4 sarcoidosis, 11 others) on the other hand. Demographical, clinical and laboratory indexes were collected. Our study aims to compare KL-6 levels between a COVID-19 population and healthy subjects or patients suffering from interstitial lung diseases (ILDs). Ultimately, we ought to determine whether KL-6 could be a marker of disease severity and bad prognosis. Results Our results showed that serum KL-6 levels in COVID-19 patients were increased compared to healthy subjects, but to a lesser extent than in patients suffering from ILD. Increased levels of KL-6 in COVID-19 patients were associated with a more severe lung disease. Discussion and conclusion Our results suggest that KL-6 could be a good biomarker to assess ILD severity in COVID-19 infection. Concerning the therapeutic response prediction, more studies are necessary.

PURPOSE OF REVIEW There is currently a heated debate ongoing whether or not to use the race coefficient for black people in the Modification of Diet in Renal Diseases and Chronic Kidney Disease Epidemiology-equation. The use of the race coefficient is thought by several American authors as a source of discrimination. RECENT FINDINGS It has recently been shown that the race coefficient is inaccurate in European and African black people. Therefore, it seems that the race correction is more a correction for black Americans, rather than for black in general. This 'correction' at the glomerular filtration rate (GFR)-level has been criticized, as it is misleading, and should be abandoned, as it has not been shown that GFR is different between black and white people. However, as differences in creatinine generation between black and white people might exist, a correction or adjustment, different for black and white people, at the creatinine level might be required, very similar to the different scaling of creatinine for males and females. SUMMARY The current debate on the race coefficient is particularly difficult because of the absence of good scientific data in black subjects and there lies the real discrimination in our opinion. We therefore call for future dedicated studies, both in Europe and USA.

Objectives In-house developed liquid-chromatography mass spectrometry (LC-MS/MS) methods are used more and more frequently for the simultaneous quantification of vitamin D metabolites. Among these, 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) is of clinical interest. This study assessed the agreement of this metabolite in two validated in-house LC-MS/MS methods. Methods 24,25(OH)2D3 was measured in 20 samples from the vitamin D external quality assurance (DEQAS) program and in a mixed cohort of hospital patients samples (n=195) with the LC-MS/MS method at the Medical University of Graz (LC-MS/MS 1) and at the University of Liège (LC-MS/MS 2). Results In DEQAS samples, 24,25(OH)2D3 results with LC-MS/MS 1 had a proportional bias of 1.0% and a negative systemic difference of −0.05%. LC-MS/MS 2 also showed a proportional bias of 1.0% and the negative systemic bias was −0.22%. Comparing the EQA samples with both methods, no systemic bias was found (0.0%) and the slope was 1%. The mean difference of 195 serum sample measurements between the two LC-MS/MS methods was minimal (−0.2%). Both LC-MS/MS methods showed a constant bias of 0.31 nmol/L and a positive proportional bias of 0.90%, respectively. Conclusions This study is the first to assess the comparability of 24,25(OH)2D3 concentrations in a mixed cohort of hospitalized patients with two fully validated in-house LC-MS/MS methods. Despite different sample preparation, chromatographic separation and ionization, both methods showed high precision measurements of 24,25(OH)2D3. Furthermore, we demonstrate the improvement of accuracy and precision measurements of 24,25(OH)2D3 in serum samples and in the DEQAS program.

This study describes concentrations of Pregnancy Associated Glycoproteins (PAG), progesterone (P4), estrone (E1) and estrone-sulfate (E1S) in American Bison sera. In 2 ranches, mature American Bison were sampled once a year for 2 yr. Subsequent American Bison cows calving days were reported. PAG concentration was determined by Radio-Immuno Assay, whereas P4, E1 and E1S were assayed using Liquid Chromatography and Mass Spectrometry. Concentrations were compared between American Bison bulls (B, n = 7), Nonpregnant cows (NP, n = 32), first (1TP, n = 3), second (2TP, n = 26) and third (3TP, n = 15) trimester of pregnancy. Seven American Bison bulls and 92 cows were sampled, 51 calved during these 2 yr. Calving occurred mostly in spring (74.5%), but also in summer (13.7%) and fall (11.8%). PAG and P4 were higher in 2TP and 3TP than B and NP (P0.0001). P4 was non-basal in B and NP. E1 and E1S were correlated (P0.0001; r = 0.76) and increased in 2TP and 3TP when compared with B and NP (P0.01). Moreover, E1S was higher in 3TP than in 2TP (P0.0001) and correlated to pregnancy day (P0.0001; r = 0.60). Breeding American Bison in Belgium induces a calving seasonality loss. P4 slowly increases in 1TP and remains steady and high in 2 and 3TP. P4 non-basal and variable concentrations in B or NP disable its use as gestation marker. American Bison produce PAG in the 2 and 3TP, but Estrone-sulfate assay seems to be the best pregnancy marker during the 2 last trimesters as it could help to estimate the gestation period.

We evaluated the quantitative DiaSorin Liaison severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen test in symptomatic and asymptomatic individuals consulting their general practitioners (GPs) during a period of stable intense virus circulation (213/100,000 habitants per day). Leftover reverse transcription-PCR (RT-PCR) positive (n=204) and negative (n=210) nasopharyngeal samples were randomly selected among fresh routine samples collected from patients consulting their GPs. Samples were tested on Liaison XL according to the manufacturer's instructions. Equivocal results were considered negative. The overall sensitivity and specificity of the Liaison antigen test compared to RTPCR were 65.7% (95% confidence interval [CI], 58.9% to 71.9%) and 100% (CI, 97.8% to 100%). Sensitivity in samples with viral loads of ≥105, ≥104, and ≥103 copies/ml were 100% (CI, 96.3% to 100.0%), 96.5% (CI, 91.8% to 98.7%), and 87.4% (CI, 81.3% to 91.5%), respectively. All samples with ≤103 copies/ml were antigen negative. The ratio of antigen concentration to viral load in samples with ≥103 copies/ml was comparable in symptomatic and asymptomatic individuals (P=0.58). The proportion of RT-PCR-positive participants with a high viral load (≥105 copies/ml) was not significantly higher in symptomatic than in asymptomatic participants (63.9% [CI, 54.9% to 72.0%] versus 51.9% [CI, 41.1% to 62.6%]; P=0.11), but the proportion of participants with a low viral load (,103 copies/ml) was significantly higher in asymptomatic than in symptomatic RT-PCR-positive participants (35.4% [CI, 25.8% to 46.4%] versus 14.3% [CI, 9.0% to 21.8%]; P, SCOPUS: ar.j, info:eu-repo/semantics/published

ispartof: JOURNAL OF NEPHROLOGY vol:34 issue:4 pages:967-969 ispartof: location:Italy status: published

Background and Aims Proteinuria, hematuria and acute kidney injury (AKI) are frequently observed in hospitalized patients with COVID-19. However, few data are available on these parameters after hospital discharge. Method This retrospective, observational and monocentric study included 153 hospitalized patients, in whom urine total proteinuria and α1-microglobulin (a marker of tubular injury) were measured. Thirty patients died. Among the 123 survivors, follow-up urine and creatinine analyses were available for 72 patients (after a median of 51 [19;93] days following hospital discharge). Results The median proteinuria at hospitalization and follow-up (n=72) was 419 [239; 748] and 79 [47; 129] mg/g, respectively (p15 mg/g (%) 88 29 Urine β2-microglobulin (n=60) (mg/L) 0.92 [0.41;4.52] 0.00 [0.00;0.00] 0.19 mg/L (%) 82 13 Hematuria (>10 per field) (%) (n=51) 19 12 ns

Background and Aims A transiliac bone biopsy is the gold standard for diagnosing renal osteodystrophy, but is not recommended as part of routine clinical workup due to its invasive nature. Suitable non-invasive alternatives have yet to be established. The aim of this study was to investigate the diagnostic accuracy novel biochemical markers of bone remodeling compared to that of biointact parathyroid hormone (PTH) for bone turnover as evaluated by histomorphometry. Method Protocolled bone biopsies were performed in end-stage kidney disease patients (ESKD, n = 80) and kidney transplant recipients (n = 119). Full-length (1-84) PTH, bone-specific alkaline phosphatase (BsAP), intact N-terminal propeptide of type I collagen (P1NP), and tartrate-resistant acid phosphatase isoform 5b (TRAP5b) were measured. Diagnostic performance was evaluated by area under the receiver operator characteristics curve (AUC). Optimal diagnostic cutoffs were established in an exploration cohort (n=100), and subsequently validated in a separate subset of patients (n=99). Results Mean age was 55±13 years, two-thirds were men (67%), and 23% had diabetes mellitus. Post-transplant eGFR was 49 [IQR 39, 59] ml/min/1.73m². Bone turnover was low in 47 (24%), normal in 119 (60%), and high in 33 (17%) patients. All biomarkers differed significantly across categories of bone turnover (p < 0.001). The AUC of biointact PTH for high turnover was 0.82 (0.73, 0.91), which was not significantly different from AUC values for BsAP, Intact P1NP, and TRAP5b (0.87, 0.90, and 0.86, respectively). AUC of biointact PTH for low turnover was 0.71 (0.63, 0.78), which was significantly lower than the values for BsAP, Intact P1NP, and TRAP5b (0.79, 0.83, and 0.79, respectively; p < 0.05, all). Calculated optimal diagnostic cutoffs in the exploration cohort are shown in Table 1. Applying these cutoffs in the validation cohort revealed high negative predictive values for both high (92 - 96%) and low (82 - 90%) bone turnover. Positive predictive values were consistently low. Conclusion The diagnostic accuracies of BsAP, Intact P1NP and TRAP5b are sufficient to rule out both high and low bone turnover in CKD. Biointact PTH shows inferior performance, particularly in kidney transplant recipients.

Background and Aims According to the KDIGO, severity of chronic kidney disease is defined by glomerular filtration rate and albuminuria. Furthermore, these variables are used for estimating both cardiovascular and end-stage renal disease risk. However, albuminuria is not always available, whereas proteinuria is, notably because of the lower costs of proteinuria. Recently, Weaver & al. developed an equation that estimates urine albumin/creatinine ratio (ACR) from protein/creatinine ratio (PCR). For retrospective analyses in clinical research, it might be interesting to be able to estimate ACR from PCR. The objective of this paper is to assess the performance of Weaver & al. ‘s equation in our population. Method In a University hospital, we retrospectively analysed measurement of ACR and PCR obtained on the same day between May 2018 and March 2020. Different assays were considered to measure urine albumin, creatinine and protein (Roche Cobas from May 2018 to May 2019 and Abbott Alinity from May 2019 to March 2020). Only one (the first available) sample per patient was considered. Patients were then categorized according to the KDIGO classification (A1-A2-A3). We then compared categorization of patients according to KDIGO between measured and estimated ACR. Sensitivity, specificity, positive predictive value and negative predictive value of estimated ACR versus measured ACR were calculated considering two different thresholds: A1 versus A2/3 (ACR 30mg/g) or A1/A2 versus A3 (ACR 300mg/g). Results Comparison was done in 2633 and 2386 patients, with Cobas and Alinity, respectively. Median age was 63 (IQR 19) and 64 (IQR 19) years old, 43 and 41% were women and 74 and 78% were diabetic (albuminuria measurement is refunded for diabetic patients in Belgium) with Cobas and Alinity, respectively. Considering measured ACR, patients were categorized in A1, A2, A3 in 65,6%, 25,5%, and 8,8%, respectively with the Cobas assay. With the Alinity assay, the results were 64,2%, 25,5%; and 10,3%, respectively. Considering estimated ACR, patients were categorized in A1, A2, A3 in 64,7%, 25,7%, and 9,6%, respectively with the Cobas Assay. With the Alinity assay, the results were 62,5%, 25,8% and 11,7%, respectively. Regarding A1-A2 (30mg/g) threshold, sensitivity was 85% and 89%, specificity was 91% and 92%, positive predictive value was 83% and 85%, negative predictive value was 92% and 94% for Cobas and Alinity respectively. Regarding A2-A3 (300mg/g) threshold, sensitivity was 93% and 98%, specificity was 98% for both, positive predictive value was 86% and 87%, negative predictive value was 99% and 99,8% for Cobas and Alinity respectively. Values are presented in table 1. Conclusion We observed a good concordance between estimated and measured ACR. Particularly, no patient in category A3 with measured ACR was categorized A1 with the estimating equations. We also observed that concordance was good regardless of our available assays. Thus, negative predictive value was excellent. In conclusion, ACR should be measured when clinically needed, but an estimated ACR can reasonably be obtained from Weaver’s equation and may provide an accurate estimation for retrospective clinical research.

ispartof: KIDNEY INTERNATIONAL REPORTS vol:5 issue:7 pages:1079-1081 ispartof: location:United States status: published

Healthy aging is defined as the process of developing and maintaining the functional ability that enables wellbeing in older age. Healthy aging is dependent upon intrinsic capacity, a composite of physical and mental capacities, and the environment an individual inhabits and their interactions with it. Maintenance of musculoskeletal health during aging is a key determinant of functional ability. Sarcopenia, osteoporosis and osteoarthritis, are a triad of musculoskeletal diseases of aging that are major contributors to the global burden of disease and disability worldwide. The prevention and management of these disorders is of increasing importance with pressure mounting from the aging population. In a new initiative, the Chinese Medical Association, Chinese Society of Osteoporosis and Bone Mineral Research, and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases jointly organized a symposium to discuss current practices and policies in the management of musculoskeletal aging. The meeting allowed experts from Europe and China to share their experience and recommendations for the management of these three major diseases. Discussing and analyzing similarities and differences in their practice should lead, through a mutual enrichment of knowledge, to better management of these diseases, in order to preserve intrinsic capacity and retard the age-related degradation of physical ability. In future, it is hoped that sharing of knowledge and best practice will advance global strategies to reduce the burden of musculoskeletal disease and promote healthy aging tailored to meet the individual patient’s needs.

Matrix-Gla-protein (MGP) is an inhibitor of vascular calcification. Its dephosphorylated and uncarboxylated inactive form, dpucMGP, is a marker of vitamin K status and of cardio-vascular outcomes in chronic kidney disease. We hypothesized that higher serum dpucMGP would be a biomarker of kidney stone disease. We measured serum dpucMGP in incident symptomatic kidney stone-formers and non-stone formers at a baseline visit. Symptomatic stone recurrence was assessed in the stones formers over a 5-year period. The association of dpucMGP with incident or recurrent kidney stones was assessed with and without adjustment for clinical, blood, and urine characteristics. There was no significant difference in serum dpucMGP level between 498 stone formers and 395 non-stone former (510 vs 501 pmol/L; p = 0.66). In a multivariable model adjusting for clinical, blood and urine chemistries, higher MGP was associated with lower risk of stone formation (OR = 0.674, 95% CI 0.522–0.870), contrary to previous reports. Among 375 stone formers with 5 years of follow-up, 79 (21%) had symptomatic recurrence. No difference in serum dpucMGP was evident in recurrent versus non-recurrent stone-formers (482 vs 502 pmol/L; p = 0.26). Serum dpucMGP was correlated with cystatin C levels in non stone-formers, incident stone-formers and recurrent stone-formers (r > 0.3, p

One of the most important tools used to evaluate kidney function in the context of chronic kidney disease or other renal function related pathologies is the exploration of glomerular filtration rate (GFR). Iohexol is up to this moment a good candidate molecule for the GFR assessment since it exhibits minimum protein binding rates and minimum extra-renal clearance, being neither secreted nor reabsorbed at the tubular level. This study proposes and evaluates a new LC-MS/MS method for the iohexol determination from capillary blood, prelevated using volumetric absorbative microsampling (VAMS) systems. As an alternative to VAMS, a brand new HemaPEN® device for micro-prelevation was also tested. A new high throughput sample preparation protocol adapted for iohexol quantification from whole blood VAMS samples was developed. The medium term stability study of iohexol in dried whole blood VAMS samples that was conducted showed a good stability of this molecule for up to 12 days. By collecting only 10 μL of blood, iohexol can be analyzed from dried whole blood VAMS samples for concentration ranges between 1 and 250 μg/mL. Due to the analyte stability in VAMS for up to 12 days, this approach might be successfully applied for GFR assessment for clinical cases allowing minimum invasiveness and even delayed analysis., Graphical abstract Image 1, Highlights • Successful VAMS-based bioanalytical method for iohexol analysis in whole human blood. • Proven medium term stability of iohexol in VAMS samples. • HemaPens as a promising alternative for iohexol analysis using only 2.74 μL of blood.

Background Biochemical bone turnover markers (BTM) are useful tools to assess bone remodeling at the cellular level. N-terminal propeptide of type I procollagen (PINP) has been recommended as a reference marker for bone formation in research studies. Methods We describe the results of a multicenter study for routine clinical laboratory assays for PINP in serum and plasma. Four centers (Athens, Greece [GR], Copenhagen, Denmark [DK], Liege, Belgium [BE] and Sheffield, United Kingdom [UK]) collected serum and plasma (EDTA) samples from 796 patients presenting to osteoporosis clinics. Specimens were analyzed in duplicate with each of the available routine clinical laboratory methods according to the manufacturers’ instructions. Passing-Bablok regressions, Bland-Altman plots, V-shape evaluation method and the concordance correlation coefficient for PINP values between serum and plasma specimens and between methods were used to determine the agreement between results. A generalized linear model was employed to identify possible variables that affected the relationship between the methods. Results We showed that both EDTA plasma and serum were suitable for PINP determination. We observed a significant proportional bias between Orion radioimmunoassay and the automated methods for PINP (Roche Cobas and IDS iSYS), which both gave very similar results. The multivariate model did not improve the excellent correlation that was observed between the methods. Conclusions Harmonization of PINP assays is possible by applying a correction factor or correctly assigning the values of the calibrators. This work will benefit from further collaboration between assays manufacturers and clinical laboratory professionals.

Summary Background The remarkable progress in the treatment of childhood acute lymphoblastic leukemia (cALL) has led to a survival rate reaching 90%. This success story is unfortunately linked to increased risk of impaired skeletal mass accumulation during childhood and adolescence, predisposing the patients to osteoporosis and pathological fractures at adulthood. Objective This study aims at characterizing the vitamin D status and bone health biomarkers in a well-characterized cohort of cALL survivors. Results Food frequency questionnaires reveal that (i) the total vitamin D intake varies greatly (44–2132 IU/d), (ii) only 16.8% of the participants consume vitamin D supplements, and (iii) 74% of survivors' intakes are below the Recommended Daily Intakes (400 IU/d). For the 42 participants taking vitamin D supplements, the median (2.5–97.5%iles) intake is 600 IU/d (21.2–1972 IU/d). Sixteen participants are vitamin D deficient ( Conclusion The present study shows that the prevalence of vitamin D insufficiency or deficiency is not greater in cALL survivors compared to the general Canadian population despite low vitamin D food and supplement intakes. Furthermore, there seem to be no overt imbalance in the gender- and age-adjusted serum bone turnover marker concentrations.

A stable isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) and 25-hydroxyvitamin D3/D2 (25(OH)D3/D2) in human aqueous humor samples from the Eye-D study. Optimum sample preparation is based on simple liquid–liquid extraction (LLE) followed by derivatization with an Amplifex reagent prior to LC-MS/MS in order to enhance analyte sensitivity. The average recoveries for 24,25(OH)2D3 (0.02, 0.05, 0.4 μg L−1), 25(OH)D3 (0.2, 0.5,3.75 μg L−1) and 25(OH)D2 (0.15, 0.4, 3 μg L−1) ranged from 92 to 112 with a coefficient of variance (CV) lower than 15%. The limits of quantitation (LOQs) were from 0.02 μg L−1 (24,25(OH)2D3) to 0.2 μg L−1 (25(OH)D3) using a sample volume of 50 μL. We demonstrated that the present method provides adequate sensitivity, selectivity, accuracy, and robustness to screen for vitamin D metabolites in aqueous humor samples by analyzing five samples which were withdrawn during cataract operation.

Background: A key role of oxidative stress has been highlighted in the pathogenesis of COVID-19. However, little has been said about oxidative stress status (OSS) of COVID-19 patients hospitalized in intensive care unit (ICU). Material and Methods: Biomarkers of the systemic OSS included antioxidants (9 assays), trace elements (3 assays), inflammation markers (4 assays) and oxidative damage to lipids (3 assays). Results: Blood samples were drawn after 9 (7–11) and 41 (39–43) days of ICU stay, respectively in 3 and 6 patients. Vitamin C, thiol proteins, reduced glutathione, γ-tocopherol, β-carotene and PAOT® score were significantly decreased compared to laboratory reference values. Selenium concentration was at the limit of the lower reference value. By contrast, the copper/zinc ratio (as a source of oxidative stress) was higher than reference values in 55% of patients while copper was significantly correlated with lipid peroxides (r = 0.95, p &lt, 0.001). Inflammatory biomarkers (C-reactive protein and myeloperoxidase) were significantly increased when compared to normals. Conclusions: The systemic OSS was strongly altered in critically ill COVID-19 patients as evidenced by increased lipid peroxidation but also by deficits in some antioxidants (vitamin C, glutathione, thiol proteins) and trace elements (selenium).

Background Serum kappa and lambda free light chains (FLC) are useful in the diagnosis, prognosis and monitoring of patients with monoclonal gammopathies. The Binding Site and Siemens were the only suppliers of kits for these analyses until recently, when Sebia introduced an enzyme-linked immunosorbent assay (ELISA) on an automated instrument, DAS AP22 ELITE. Method Samples from routine analysis, controls and chronic kidney disease (CKD) patients were tested using the automated version of Sebia FLC ELISA with the AP22 ELITE and results were compared with Freelite on the SPA PLUS (The Binding Site). Results Sebia FLC ELISA showed a good performance using the AP22 ELITE. A concordance of 82% was found with the results obtained with Freelite. Sebia FLC is a reproducible assay, requiring less retesting than Freelite thanks to a broader range. Earlier findings that the results obtained are closer to the FLC monoclonal band measured by electrophoresis were confirmed. Higher kappa and lambda values obtained in CKD individuals were also shown, confirming that a kappa/lambda FLC ratio should be introduced by Sebia for CKD patients, as with The Binding Site. Conclusions Sebia put forward new technology that automatically measures free light chains. This technique is suitable for routine use; however, the results cannot be used interchangeably with Freelite kits.

Chronic kidney disease and osteoporosis are major public health problems associated with an aging population. Vitamin K insufficiency is prevalent among patients with end-stage renal disease (ESRD). Preliminary data indicate that poor vitamin K status may compromise bone health and that increased inflammation may be in the causal pathway. We performed an ancillary analysis of data collected in the frame of prospective observational cohort studies exploring various aspects of bone health in de novo renal transplant recipients to investigate the association between vitamin K status, inflammation, bone mineral density, and incident clinical fractures. Parameters of mineral metabolism (including biointact PTH and FGF23, sclerostin, calcidiol, calcitriol) and inflammation (CRP and IL-6), osteoprotegerin, bone turnover markers (P1NP, BsAP, and TRAP5B), and dephosphorylated-uncarboxylated Matrix Gla Protein (dp-ucMGP) were assessed on blood samples collected immediately prior to kidney transplantation in 468 patients. Areal bone mineral density (aBMD) was measured at the lumbar spine and femoral neck by dual-energy X-ray absorptiometry within 14 days posttransplant. Poor vitamin K status, defined by dp-ucMGP >500 nmol/L, was highly prevalent (90%). High dp-ucMGP levels independently associated with elevated inflammatory markers and low aBMD. No associations were observed between vitamin K status and bone turnover markers. During a median follow-up of 5.1 years, 33 patients sustained a fragility fracture. In Cox-proportional hazards analysis, a dp-ucMGP above median associated with incident fractures, independent of classical determinants, including age, gender, history of fracture, and aBMD (HR 2.21; 95% CI, 1.00 to 4.91; p

Urinary proteins or urinary albumin exhibit a high intra individual variability. Therefore, urine collected during 24 hours has been recognized as a reference biological fluid for usual values determination. However, urine collection during a day is difficult and numerous studies have been performed to replace the "gold standard" with measures on random samples and results given as protein/creatinine ratio or albumin/creatinine ratio, to decrease the variability. The paper presents the populations where ratios are well correlated with protein excretion, the cut-off values recommended in clinical settings and the limits of using ratio rather than 24 h excretion.

The data contained in this article are related to the article entitled “Case report: Uncommon Sulfamethoxazole Crystalluria” (Castiglione et al., 2018). Sulfamethoxazole crystalluria is very rare and crystals identification is complex (de Liso et al., 2016). We identified seven patients with uncommon urine crystals that were composed of N-Acetyl-Sulfamethoxazole. Three of the patients developed an acute renal failure simultaneously to crystalluria. Hence, this data article describes the method of crystals identification thanks to infrared spectroscopy. The relevant clinical data of patients, including medical history, drug dosage and urine parameters related to the crystalluria are presented. Keywords: Sulfamethoxazole, Crystalluria, Drug: adverse effect, Acute renal failure, Infrared spectrophotometry, Urine microscopy

Background Sub-Saharan Africans exhibit a higher frequency of chronic kidney disease (CKD) than other populations. In this study, we sought to determine the frequency of apolipoprotein L1 (APOL1) genotypes in hypertension-attributed CKD in Kinshasa, Democratic Republic of the Congo. Methods We performed a case-control study identifying 162 subjects: 79 with hypertension-attributed CKD and 83 controls living in Kinshasa who were genotyped for APOL1 risk variants between July 2013 and November 2016. We selected control subjects from the general population and matched them with the cases according to age. Logistic regression analysis was used to examine the relationship between APOL1 high-risk genotypes and CKD. Results The frequencies of the APOL1 G1 and G2 alleles were 19.1 and 7.1%, respectively. The number of individuals with the G1 and G2 risk alleles was significantly higher in the CKD group (12.7%) than in the control group (2.4%), particularly in individuals with end-stage kidney disease (14.3%). Subjects carrying two risk alleles was strongly and independently associated with hypertension-attributed nephropathy, with an adjusted odds ratio of 7.7 (95% confidence interval 1.5-39.7; P = 0.014). The high-risk APOL1 genotypes were G1/G1 and G1/G2, whereas G2/G2 was not found in the study population. Conclusions The results of this study demonstrate the association of high-risk APOL1 genotypes with kidney disease in Kinshasa. The absence of G2/G2 may be consistent with powerful selective sweeps induced by Trypanosoma brucei gambiense infection. In contrast, the presence of APOL1 G2/G2 among individuals of African ancestry in the USA may indicate relaxation of natural selection in a trypanosome-free environment.

An intralaboratory study assessing assay variability and bias for determination of serum total 25-hydroxyvitamin D [25(OH)D] was conducted by the Vitamin D Standardization Program (VDSP). Thirteen assays for serum total 25(OH)D were evaluated in a single laboratory including 11 unique immunoassays and one liquid chromatography – tandem mass spectrometry (LC-MS/MS) assay. Fifty single-donor serum samples, including eight samples with high concentrations of 25(OH)D(2) (> 30 nmol/L), were assigned target values for 25(OH)D(2) and 25(OH)D(3) using reference measurement procedures (RMP). Using four replicate measurements for each sample, the mean total percent coefficient of variation (%CV) and mean % bias from the target values were determined for each assay using the 50 single-donor samples and a 42-sample subset, which excluded 8 high 25(OH)D(2) concentration samples, and compared with VDSP performance criteria of ≤ 10% CV and ≤ ±5% mean bias. All 12 assays achieved the performance criterion for %CV, and 9 of the 12 assays were within ≤ ±5 % mean bias. The Fujirebio Inc. assay exhibited the lowest %CV and highest percentage of individual measurements within ≤ ±5% mean bias. Ten immunoassays exhibited changes in response due to the high 25(OH)D(2) samples with Abbott, Biomérieux, DiaSorin, DIAsource, and IDS-iSYS assays having the largest deviations. The Fujirebio Inc. and Beckman Coulter assays were only minimally affected by the presence of the high 25(OH)D(2) samples. Samples with high concentrations of 25(OH)D(2) provided a critical performance test for immunoassays indicating that some assays may not have equal response or recovery for 25(OH)D(2) and 25(OH)D(3).

Background Proteinuria has been commonly reported in patients with COVID-19. However, only dipstick tests have been frequently used thus far. Here, the quantification and characterization of proteinuria were investigated and their association with mortality was assessed. Methods This retrospective, observational, single center study included 153 patients, hospitalized with COVID-19 between March 28th and April 30th, 2020, in whom total proteinuria and urinary α1-microglobulin (a marker of tubular injury) were measured. Association with mortality was evaluated, with a follow-up until May 7th, 2020. Results According to the Kidney Disease Improving Global Outcomes staging, 14% (n = 21) of the patients had category 1 proteinuria (1-microglobulin concentration was higher than 15 mg/g in 89% of patients. After a median follow-up of 27 [14;30] days, the mortality rate reached 18%. Total proteinuria and urinary α1-microglobulin were associated with mortality in unadjusted and adjusted models. This association was stronger in subgroups of patients with normal renal function and without a urinary catheter. Conclusions Proteinuria is frequent in patients with COVID-19. Its characterization suggests a tubular origin, with increased urinary α1-microglobulin. Tubular proteinuria was associated with mortality in COVID-19 in our restropective, observational study.

Measured glomerular filtration rate (mGFR) measurement is necessary in specific patients and/or specific clinical contexts.1–3 Plasma clearances are the preferred methods, as they are less costly and cumbersome than urinary clearances.4 The contrast medium iohexol is the most commonly used worldwide, partly for pragmatic reasons, as this marker is stable, not radioactive, and its measurement is easy, with the possibility of an external quality control.1,4

In this narrative review, the role of vitamin D deficiency in the pathophysiology, healing of fragility fractures, and rehabilitation is discussed. Vitamin D status can be assessed by measuring serum 25(OH)-vitamin D level with standardized assays. There is a high prevalence of vitamin D insufficiency (25(OH)D < 50 nmol/l (i.e., 20 ng/mL)) or deficiency (25(OH)D < 25 nmol/l (i.e., 10 ng/mL)) in patients with fragility fractures and especially in those with a hip fracture. The evidence on the effects of vitamin D deficiency and/or vitamin D supplementation on fracture healing and material osseointegration is still limited. However, it appears that vitamin D have a rather positive influence on these processes. The fracture liaison service (FLS) model can help to inform orthopedic surgeons, all caregivers, and fractured patients about the importance of optimal vitamin D status in the management of patients with fragility fractures. Therefore, vitamin D status should be included in Capture the Fracture (R) program as an outcome of FLS in addition to dual-energy X-ray absorptiometry (DXA) and specific antiosteoporosis medication. Vitamin D plays a significant role in the pathophysiology and healing of fragility fractures and in rehabilitation after fracture. Correction of vitamin D deficiency should be one of the main outcomes in fracture liaison services.

Introduction L’insuffisance renale chronique est definie par le debit de filtration glomerulaire et l’albuminurie. Ces variables sont egalement utilisees pour apprecier risque cardiovasculaire et d’insuffisance renale terminale. L’albuminurie est souvent indisponible. Weaver et al. [1] ont developpe une equation estimant le ratio albumine/creatinine(ACR) au depart du ratio proteine/creatinine(PCR). Nous evaluons la performance de l’equation dans notre population. Description Dans un CHU, nous avons analyse retrospectivement les mesures d’ACR (ACRm) et PCR (PCRm) obtenus sur meme echantillon sur deux analyseurs (Roche Cobas 2018-2019 ; Abbott Alinity 2019-2020). Methodes Les patients furent classes selon KDIGO (A1-A2-A3). Nous avons ensuite compare les classifications KDIGO des ACRe et ACRm obtenus. La sensibilite, specificite, valeur predictive positive (VPP) et valeur predictive negative (VPN) de l’ACRe contre ACRm furent calculees selon les valeurs seuils : A1/A2 contre A3 (30 mg/g) ou A1 contre A2/3 (300 mg/g). Resultats 2633 et 2386 ACRm et PCRm ont ete realisees sur Roche et Abbott, respectivement. L’âge moyen etait 63 et 64 ans ; 43 et 41 % etaient des femmes ; 74 et 78 % etaient diabetiques avec Roche et Abbott, respectivement. La proportion de patient avec ACRm-A1 etait 65,6/64,2 % ; A2 25,5/25,5 % ; A3 8,8/10,3 % (Roche/Abbott respectivement). La proportion de patient avec un ACRe-A1 etait 64,7/62,5 % ; A2 25,7/25,8 % ; A3 9,6/11,7 % (Roche/Abbott respectivement). S’agissant du seuil 30 mg/g, la sensibilite etait 85/89 %, specificite 91/92 %, VPP 83/85 %, VPN 92/94 % (Roche/Abbott respectivement). Pour le seuil 300 mg/g, la sensibilite etait 93/98 %, specificite 98/98 %, VPP 86/87 %, VPN 99/99,8 % (Roche/Abbott respectivement) ( Tableau 1 ). Conclusion Une bonne concordance fut observee entre ACRe et ACRm par l’equation de Weaver. Aucun patient avec un ACRm-A3 n’a ete classe en ACRe-A1 par l’equation. La VPN est donc excellente. En conclusion, l’ACR doit etre mesure en pratique clinique lorsque requis, mais un ACRe peut raisonnablement etre obtenu a partir d’un PCR avec l’equation de Weaver et fourni une estimation precise a des fins de recherche retrospective.

Introduction Glomerular filtration rate (GFR) is measured from the late plasma disappearance curve of an exogenous tracer, after correction for the early decay—corresponding to the distribution of the tracer—using various equations. These equations display the highest discrepancies in the GFR range above 90 ml/min per 1.73 m2, and their respective performances against a reference, urinary GFR measurement are unclear. Methods In patients with mGFR >90 ml/min per 1.73 m2 from 6 different cohorts, we compared GFR obtained from the plasma clearance of iohexol or 51Cr-ethylenediamine tetraacetic acid (EDTA), after correction using Chantler (C), Bröchner-Mortensen (BM), Fleming (F), Jodal-Bröchner-Mortensen (JBM), and Ng (N) equations, with urinary clearance of the same tracers or inulin. Results In 438 participants (median age 41 [39–42] years, 43% women), the median urinary clearance was 100.8 (94.7–112.6) ml/min per 1.73 m2. Plasma clearances using the correction equations were 105.7 (96.8–119.2), 102.4 (95.2–112.9), 100.7 (93.6–111.1), 102.6 (95.2–113.4), and 106.0 (98.2–117.6) ml/min per 1.73 m2 for C, BM, F, JBM, and N, respectively. Concordance correlation coefficients between plasma and urinary clearances were poor for all equations. Compared with urinary clearances, BM, F, and JBM displayed the best accuracy within 10% (73%, 72%, and 71%, respectively, vs. 63% and 66% for C and N), whereas BM and JBM had the lowest median biases. Accuracy of all equations was especially low in the hyperfiltration range (urinary clearance >130 ml/min per 1.73 m2). Conclusion The BM and JBM equations displayed the best overall performances to correct for the early disappearance curve. Results of these equations should be interpreted with caution, especially in the highest GFR range., Graphical abstract