Acute kidney injury in critical COVID-19 patients: usefulness of urinary biomarkers and kidney proximal tubulopathy.

Tubular injury is the main cause of acute kidney injury (AKI) in critically ill COVID-19 patients. Proximal tubular dysfunction (PTD) and changes in urinary biomarkers, such as NGAL, TIMP-2, and IGFBP7 product ([TIMP-2]•[IGFBP7]), could precede AKI. We conducted a prospective cohort study from 2020/03/09 to 2020/05/03, which consecutively included all COVID-19 patients who had at least one urinalysis, to assess the incidence of PTD and AKI, and the effectiveness of PTD, NGAL, and [TIMP-2]•[IGFBP7] in AKI and persistent AKI prediction using the area under the receiver operating characteristic curves (AUCs), Kaplan-Meier methodology (log-rank tests), and Cox models. Among the 60 patients admitted to the ICU with proven COVID-19 (median age: 63-year-old (interquartile range: IQR, 55-74), 45 males (75%), median simplified acute physiology score (SAPS) II: 34 (IQR, 22-47) and median BMI: 25.7 kg/m2 (IQR, 23.3-30.8)) analyzed, PTD was diagnosed in 29 patients (48%), AKI in 33 (55%) and persistent AKI in 20 (33%). Urinary NGAL had the highest AUC for AKI prediction: 0.635 (95%CI: 0.491-0.779) and persistent AKI prediction: 0.681 (95%CI: 0.535-0.826), as compared to PTD and [TIMP-2]•[IGFBP7] (AUCs <0.6). AKI was independently associated with higher SAPSII (HR = 1.04, 95%CI: 1.01-1.06, p = 0.005) and BMI (HR = 1.07, 95%CI: 1.00-1.14, p = 0.04) and persistent AKI with higher SAPSII (HR = 1.03, 95%CI: 1.00-1.06, p = 0.048) and nephrotoxic drug use (HR = 3.88, 95%CI: 1.20-12.5, p = 0.02). In conclusion, in critically ill COVID-19 patients, the incidence of PTD and AKI was relatively high. NGAL was the best urinary biomarker for predicting AKI, but only clinical severity was independently associated with its occurrence.

Comparison of four immunoassays to an HPLC method for the therapeutic drug monitoring of methotrexate: Influence of the hydroxylated metabolite levels and impact on clinical threshold.

OBJECTIVES: Methotrexate requires therapeutic drug monitoring in oncology because of narrow therapeutic index, especially the metabolite 7-hydroxymethotrexate exhibits nephrotoxicity. The goal of this study was to evaluate different assays and their impact on clinical decisions. METHODS: Following routine measurement with Abbott TDxFLx® assay (MTX-TDX), 62 samples were analysed on Architect®i1000 (MTX-ARCHI), Xpand® (ARK/XPND), Indiko® (ARK/INDI), and HPLC (MTX-HPLC) as the reference method. The influence of 7-hydroxymethotrexate was explored on ARK reagent to document the cause of the observed bias. ROC curves were built to study the impact of the method on the discharge thresholds for the patients at three levels. RESULTS: Total imprecision was below 2.60% for the methotrexate-ARCHI and close to 10% for both ARK assays for plasma pools. The correlation coefficients were 0.93, 0.93, 0.89 and 0.95, the Bland-Altman difference plot revealed a bias of 0.075, 0.037, 0.049 and -0.002, and the number of results exceeding the TE criteria of 0.1 µM was 17 (27%), 13 (21%), 15 (24%) and 15 (24%) for MTX-TDX, ARK/INDI, ARK/XPND and MTX-ARCHI, respectively. Cross reactivity with 7-hydroxymethotrexate was between 1 and 9%. Overestimation of methotrexate concentration was between -4% and +32%. The most robust clinical level was found to be the highest level (0.2 µM) with ROC curves. CONCLUSIONS: The authors found the best results for imprecision with chemiluminescent microparticle immunoassay method on methotrexate-ARCHI, with bias below to the RICOS recommendations and best correlation to the reference method. Impact on the threshold values for clinical decision need to be clearly exposed to clinicians.

Long term pronostic value of suPAR in chronic heart failure: reclassification of patients with low MAGGIC score.

OBJECTIVES: Inflammation is a hallmark of heart failure (HF) and among inflammatory biomarkers, the most studied remains the C-reactive protein (CRP). In recent years several biomarkers have emerged, such as sST2 and soluble urokinase-type plasminogen activator receptor (suPAR). This study set out to examine the relative importance of long-time prognostic strength of suPAR and the potential additive information on patient risk with chronic HF in comparison with pronostic value of CRP and sST2. METHODS: Demographics, clinical and biological variables were assessed in a total of 182 patients with chronic HF over median follow-up period of 80 months. Inflammatory biomarkers (i.e., CRP, sST2, and suPAR) were performed. RESULTS: In univariate Cox regression analysis age, NYHA class, MAGGIC score and the five biomarkers (N-terminal pro brain natriuretic peptide [NT-proBNP], high-sensitive cardiac troponin T [hs-cTnT], CRP, sST2, and suPAR) were associated with both all-cause and cardiovascular mortality. In the multivariate model, only NT-proBNP, suPAR, and MAGGIC score remained independent predictors of all-cause mortality as well as of cardiovascular mortality. Risk classification analysis was significantly improved with the addition of suPAR particularly for all-cause short- and long-term mortality. Using a classification tree approach, the same three variables could be considered as significant classifier variables to predict all-cause or cardiovascular mortality and an algorithm were reported. We demonstrated the favorable outcome associated with patients with a low MAGGIC score and a low suPAR level by comparison to patients with low MAGGIC score but high suPAR values. CONCLUSIONS: The main findings of our study are (1) that among the three inflammatory biomarkers, only suPAR levels were independently associated with 96-month mortality for patients with chronic HF and (2) that an algorithm based on clinical score, a cardiomyocyte stress biomarker and an inflammatory biomarker could help to a more reliable long term risk stratification in heart failure.

Quantitative assessment of sodium mass removal using ionic dialysance and sodium gradient as a proxy tool: Comparison of high-flux hemodialysis versus online hemodiafiltration.

Restoration and maintenance of sodium are still a matter of concern and remains of critical importance to improve the outcomes in homeostasis of stage 5 chronic kidney disease patients on dialysis. Sodium mass balance and fluid volume control rely on the "dry weight" probing approach consisting mainly of adjusting the ultrafiltration volume and diet restrictions to patient needs. An additional component of sodium and fluid management relies on adjusting the dialysate-plasma sodium concentration gradient. Hypotonicity of ultrafiltrate in online hemodiafiltration (ol-HDF) might represent an additional risk factor in regard to sodium mass balance. A continuous blood-side approach for quantifying sodium mass balance in hemodialysis and ol-HDF using an online ionic dialysance sensor device ("Flux" method) embedded on hemodialysis machine was explored and compared to conventional cross-sectional "Inventory" methods using anthropometric measurement (Watson), multifrequency bioimpedance analysis (MF-BIA), or online clearance monitoring (OCM) to assess the total body water. An additional dialysate-side approach, consisting of the estimation of inlet/outlet sodium mass balance in the dialysate circuit was also performed. Ten stable hemodialysis patients were included in an "ABAB"-designed study comparing high-flux hemodialysis (hf-HD) and ol-HDF. Results are expressed using a patient-centered sign convention as follows: accumulation into the patient leads to a positive balance while recovery in the external environment (dialysate, machine) leads to a negative balance. In the blood-side approach, a slight difference in sodium mass transfer was observed between models with hf-HD (-222.6 [-585.1-61.3], -256.4 [-607.8-43.7], -258.9 [-609.8-41.3], and -258.5 [-607.8-43.5] mmol/session with Flux and Inventory models using VWatson , VMF-BIA , and VOCM values for the volumes of total body water, respectively; global P value < .0001) and ol-HDF modalities (-235.3 [-707.4-128.3], -264.9 [-595.5-50.8], -267.4 [-598.1-44.1], and -266.0 [-595.6-55.6] mmol/session with Flux and Inventory models using VWatson , VMF-BIA , and VOCM values for the volumes of total body water, respectively; global P value < .0001). Cumulative net ionic mass balance on a weekly basis remained virtually similar in hf-HD and ol-HDF using Flux method (P = n.s.). Finally, the comparative quantification of sodium mass balance using blood-side (Ionic Flux) and dialysate-side approaches reported clinically acceptable (a) agreement (with limits of agreement with 95% confidence intervals (CI): -166.2 to 207.2) and (b) correlation (Spearman's rho = 0.806; P < .0001). We validated a new method to quantify sodium mass balance based on ionic mass balance in dialysis patients using embedded ionic dialysance sensor combined with dialysate/plasma sodium concentrations. This method is accurate enough to support caregivers in managing sodium mass balance in dialysis patients. It offers a bridging solution to automated sodium proprietary balancing module of hemodialysis machine in the future.

Evaluation of a new point-of-care testing for creatinine and urea measurement.

Point of care testing makes it possible to obtain results in an extremely short time. Recently, radiometer has expanded the panel of tests available on its ABL90 FLEX PLUS blood gas analyzer (ABL90) by adding urea and creatinine. The aim of this study was to verify the performance of these new parameters. This included assessment of imprecision, linearity, accuracy by comparison with central laboratory standard assays and interferences. In addition, clinical utility in a dialysis center was evaluated. Within-lab coefficients of variation were close to 2%. The mean and limits of agreement (mean ± 1.96 SD) of the difference between ABL90 and Roche enzymatic assays on cobas 8000 were 0.5 (from -1.4 to 2.3) mmol/L and -0.9 (from -19.5 to 17.8) µmol/L for urea and creatinine, respectively. The ABL90 enzymatic urea and creatinine assays met the acceptance criteria based on biological variation for imprecision and showed good agreement with central laboratory. The two assays were unaffected by hematocrit variation between 20 and 70%, hemolysis and icterus interferences. It should be noted that the relationship between lab methods and ABL90 was conserved even for high pre-dialysis values allowing easy access to dialysis adequacy parameters (Kt/V) and muscle mass evaluation (creatinine index). Rapid measurement of creatinine and urea using whole blood specimens on ABL90 appears as a fast and convenient method. Analytical performances were in accordance with our expectations without any significant interferences by hemolysis or icterus.

Reversibility of Acute Kidney Injury in Medical ICU Patients: Predictability Performance of Urinary Tissue Inhibitor of Metalloproteinase-2 x Insulin-Like Growth Factor-Binding Protein 7 and Renal Resistive Index.

OBJECTIVES: Urinary biomarkers and renal Doppler sonography remain considered as promising tools to distinguish transient from persistent acute kidney injury. The performance of the urinary biomarker, tissue inhibitor of metalloproteinase-2 x insulin-like growth factor-binding protein 7 and of renal resistive index to predict persistent acute kidney injury showed contradictory results. Our aim was to evaluate the performance of tissue inhibitor of metalloproteinase-2 x insulin-like growth factor-binding protein 7 and renal resistive index in predicting reversibility of acute kidney injury in critically ill patients. DESIGN: Prospective observational study. SETTING: Twenty-bed medical ICU in an university hospital. PATIENTS: Consecutive patients with acute kidney injury. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Renal resistive index was measured within 12 hours after admission, and urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 was measured at H0, H6, H12, and H24. Renal dysfunction reversibility was evaluated at day 3. Receiver operating characteristic curves were plotted to evaluate diagnostic performance of renal resistive index and tissue inhibitor of metalloproteinase-2 x insulin-like growth factor-binding protein 7 to predict a persistent acute kidney injury. Overall, 100 patients were included in whom 50 with persistent acute kidney injury. Renal resistive index was higher in persistent acute kidney injury group. Urinary tissue inhibitor of metalloproteinase-2 x insulin-like growth factor-binding protein 7 was not significantly different at each time between both groups. The performance of tissue inhibitor of metalloproteinase-2 x insulin-like growth factor-binding protein 7 was poor with respectively an area under the receiver operating characteristic curves of 0.57 (95% CI, 0.45-0.68), 0.58 (95% CI, 0.47-0.69), 0.61 (95% CI, 0.50-0.72), and 0.57 (95% CI, 0.46-0.68) at H0, H6, H12, and H24. The area under the receiver operating characteristic curve for renal resistive index was 0.93 (95% CI, 0.89-0.98). A renal resistive index greater than or equal to 0.685 predicting persistent acute kidney injury with 78% (95% CI, 64-88%) sensitivity and 90% (95% CI, 78-97%) specificity. CONCLUSIONS: Renal resistive index had a good performance for predicting the reversibility of acute kidney injury in critically ill patients. Urinary tissue inhibitor of metalloproteinase-2 x insulin-like growth factor-binding protein 7 was unable to differentiate transient from persistent acute kidney injury.

Determination of hemolysis cut-offs for biochemical and immunochemical analytes according to their value.

Background All general biochemistry instruments allow the measure of hemolysis index (HI), and suppliers provide an acceptable HI for each assay without consideration of the analyte value or its clinical application. Our first objective was to measure the impact of hemolysis degree on plasma biochemical and immunochemical analytes to determine the maximum allowable HI for each of them using four calculation methods as significant bias in comparison to manufacturer's data. The second objective was to assess whether the maximum allowable HI varied according to the analyte values. Methods Twenty analytes were measured in hemolyzate-treated plasma to determine the HI leading to a significant change compared to baseline value. Analytes were assessed at one (3 analytes), two (5 analytes) and three (12 analytes) values according to their sensitivity to hemolysis and their clinical impact. We used four calculation methods as significant limit from baseline value: the total change limit (TCL), the 10% change (10%Δ), the analytical change limit and the reference change value. Results Allowable HI was significantly different according to the threshold chosen for most analytes and was also dependent on the analyte value for alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, creatine kinase, iron, haptoglobin and high sensitivity troponin T. No hemolysis interference was observed for albumin, creatinine, C-reactive protein, and procalcitonin even at an HI value of 11 g/L. Conclusions This study highlights that TCL is the most appropriate calculation method to determine allowable HI in practice for biochemical and immunochemical parameters using Cobas 8000© from Roche Diagnostics. In addition, different allowable HI were found according to analyte value leading to optimization of resampling to save time in patient care.

Analytical evaluation of the novel VITROS BRAHMS procalcitonin immunoassay.

To determine the analytical performance of Novel VITROS BRAHMS Procalcitonin Immunoassay on VITROS 3600 and correlation with BRAHMS PCT sensitive KRYPTOR reference method. Analytical performances including imprecision studies, linearity, limit of detection (LoD) and determination of hemolysis index were performed for VITROS BRAHMS PCT assay. Imprecision was assessed on plasma pool and internal control with 2 levels. The method comparison was performed using 162 plasma obtained from clinical departments. The total imprecision was acceptable and all CV were <5%. The LoD was in accordance with manufacturer's claims. The equation of linearity in the lower range was found to be y = 1.0014x - 0.0091, with r2 = 1. No interference to hemoglobin up to 11 g/L was observed. Correlation studies showed a good correlation between PCT measurements using VITROS BRAHMS PCT assay against KRYPTOR system including for values lower than 2 µg/L. The novel VITROS BRAHMS PCT assay from OrthoClinical Diagnostics shows analytical performances acceptable for clinical use. In addition, the concordance with KRYPTOR method was fine at all clinical cut-offs.

Estimation of residual renal function using beta-trace protein: Impact of dialysis procedures.

Beta-trace protein (BTP), a low molecular weight protein of 23-29 kDa, has been proposed as a promising biomarker to estimate residual renal function (RRF) in patients on maintenance hemodialysis (HD). Indeed, BTP is cleared by native kidney but not during conventional HD session. By contrast, the removal rate of BTP using convective processes (mainly hemodiafiltration [HDF]) and peritoneal dialysis (PD) has been little or not investigated. Therefore, an aim of this study was to evaluate the impact of dialysis procedures (high-flux HD, on-line post-dilution HDF and PD) on BTP removal in comparison with beta-2 microglobulin (B2M) and cystatin C (CYSC) removals after a single session. In addition, the ability of BTP to predict RRF in PD was assessed. This observational cross-sectional study included a total of 82 stable chronic kidney disease patients, 53 patients were on maintenance dialysis (with n = 26 in HD and n = 27 in HDF) and 29 were on PD. Serum concentrations of BTP, B2M, and CYSC were measured (a) before and after a single dialysis session in HD and HDF anuric patients to calculate reduction percentages, (b) in serum, 24-hour-dialysate and 24-hour-urine in PD patients to compute total, peritoneal, and urinary clearance. RRF was estimated using four equations developed for dialysis patients without urine collection and compared to the mean of the urea and creatinine clearances in PD. The concentrations of the three studied molecules were significantly reduced (P < .001) after dialysis session with significantly higher reduction ratio using HDF compared to HD modality (P < .001): BTP 49.3% vs 17.5%; B2M 82.3% vs 69.7%; CYSC 77.4% vs 66% in HDF and HD, respectively. In non-anuric PD patients, B2M and CYSC were partly removed by peritoneal clearance (72.3% and 57.6% for B2M and CYSC, respectively). By contrast, BTP removal by the peritoneum was negligible and a low bias for the BTP-based equation to estimate RRF (-1.4 mL/min/1.73 m2 ) was calculated. BTP is significantly removed by high-flux HD or HDF, thereby compromising its use to estimate RRF. By contrast, BTP appears as a promising biomarker to estimate RRF in PD patients since it is not affected by peritoneal clearance, unlike B2M and CYSC, and it is well correlated to RRF.

Moving from the second to the third generation Roche PTH assays: what are the consequences for clinical practice?

Background The determination of parathyroid hormone (PTH) is essential for exploring phosphocalcic disorders especially in patients with renal failure. At present, second or third generation PTH assays are available on the market from Roche Diagnostics as well as from others companies but the lack of standardization has complicated the interpretation. Methods We wanted to assess the clinical impact by measuring the PTH levels with the two generations concomitantly on different groups of populations including 46 healthy, 103 pre-dialyzed and 73 hemodialyzed (HD) patients. Results In healthy subjects, the PTH concentrations were not different whatever the generation used, whereas beyond 200 pg/mL, we reported an overestimation of the second generation PTH. In patients with chronic kidney disease (CKD) stage 3-5 the observed differences between the two generations increase with increasing PTH levels and decreasing glomerular filtration rate (GFR). Classification according to the kidney disease: improving global outcomes (KDIGO) revealed a high percentage of discordant results between the two generations (κ coefficient <0.20). These discrepancies are clinically relevant as PTH levels remain the cornerstone for diagnosis and treatment of the CKD-mineral and bone disorder (CKD-MBD). Conclusions The introduction of a new PTH assay generation in clinical practice should be carried out with caution.

Stability of routine biochemical analytes in whole blood and plasma/serum: focus on potassium stability from lithium heparin.

BACKGROUND: Blood specimens are transported from clinical departments to the biochemistry laboratory by hospital courier service, sometimes over long distances. The aim of this study was to assess the stability of common biochemical analytes in venous blood under our routine transport conditions and to evaluate analyte stability after prompt or delayed centrifugation. METHODS: We investigated pre- and postanalytical contributions of 32 biochemical analytes in plasma and serum samples from 10 patients (healthy adults and patients from intensive care units). Differences in analyte concentrations between baseline (T0) and different time intervals (2, 4, 6, 8, 12 and 24 h) following storage after prompt and delayed centrifugation were reported. Evaluation was against the total change limit as described by Oddoze et al. (Oddoze C, Lombard E, Portugal H. Stability study of 81 analytes in human whole blood, in serum and in plasma. Clin Biochem 2012;45:464-9). RESULTS: The majority of analytes were stable with delayed separation up to 12 h, except for potassium, C-peptide, osteocalcin, parathyroid hormone (PTH), bicarbonate and LDH. After prompt centrifugation and storage at 4°C, stability was greatly increased up to 48 h for most analytes. LDH and bicarbonate had the lowest stability after centrifugation; therefore, no reanalysis of these analytes in a centrifuged tube can be allowed. CONCLUSIONS: Knowledge of analyte stability is crucial to interpret biological analysis with confidence. However, centrifugation prior to transport is time consuming, and the transfer of plasma or serum from a primary tube to a secondary tube increases the risk of preanalytical errors. For analytes that are stable in whole blood for 24 h or more, it seems that there is no benefit to centrifuge before transport.

Continuous Veno-Venous High Cut-Off Hemodialysis Compared to Continuous Veno-Venous Hemodiafiltration in Intensive Care Unit Acute Kidney Injury Patients.

AIMS: High cut-off (HCO) continuous veno-venous hemodialysis (CVVHD) was compared to high-flux membrane (HFM) continuous veno-venous hemodiafiltration (CVVHDF) in intensive care unit (ICU) acute kidney injury (AKI) in terms of efficiency, hemodynamic tolerance, medium-sized molecules removal, albumin loss, and inflammatory system activation. METHODS: In a prospective cross-over randomized study, 10 AKI patients underwent successively HCO (Ultraflux EmiC2: ß2-microglobulin [ß2M] sieving coefficient [SC]: 0.9) CVVHD and HFM (Ultraflux AV1000S: ß2M SC: 0.65) -CVVHDF. RESULTS: Over the 20 sessions, hypotensive and febrile episodes, reduction rates of urea, creatinine, and ß2M were similar in both modalities. Though dialysis dose was higher with CVVHDF (36 ± 4 vs. 21 ± 6 mL/Kg/h), urea, creatinine, and ß2M instantaneous and plasmatic clearances did not differ except for urea at 12 h. Protein loss, superoxide anion production, cytokines, and growth factors variations were also comparable. CONCLUSION: HCO CVVHD is well tolerated and is as effective as HFM CVVHDF in clearance of solutes and removal of ß2M. It induces neither protein loss nor overproduction of superoxide anion. Video Journal Club "Cappuccino with Claudio Ronco" at http://www.karger.com/?doi=489082.

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.

Evaluation of the New Siemens Tacrolimus Assay on the Dimension EXL Integrated Chemistry System Analyzer: Comparison With an Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry Method.

BACKGROUND: Many patients are maintained at the lower end of the tacrolimus (TAC) reference range (3-7 ng/mL), requiring the use of analytical methods displaying a very low limit of quantification for their follow-up. Therefore, the new Dimension TAC, based on affinity chrome-mediated immunoassay technology, was evaluated on the Dimension EXL Integrated Chemistry System (Siemens Healthcare Diagnostics Inc). The aims of this study were (1) to evaluate the analytical performances with special emphasis on sensibility at low levels of TAC, (2) to compare the results with an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC/MS/MS) method. METHODS: Analytical performance (imprecision, linearity, limit of detection, and limit of quantification) was evaluated. Comparison to UPLC/MS/MS was performed on 106 whole blood samples from 88 transplant recipients using regression analysis and Bland-Altman plot analysis. RESULTS: Repeatability and within-laboratory coefficients of variation were <6% at mean TAC control levels of 3.7, 11.7, and 19.2 ng/mL. Linearity was confirmed between 1.0 and 22 ng/mL. Passing-Bablok regression analysis of Siemens TAC assay in comparison with UPLC/MS/MS values displayed a slope of 1.09 and an intercept of -0.42. Using Bland-Altman analysis, the mean bias was 0.27 ng/mL with 1.96 SD limits of -2.14 and 2.67 ng/mL. CONCLUSIONS: The new Dimension TAC immunoassay on the EXL analyzer demonstrated reliable and reproducible performances allowing routine monitoring in transplant patients, even at TAC concentrations at the lower end of the therapeutic range.

Cardiovascular risk stratification in hemodialysis patients in the era of highly sensitive troponins: should we choose between hs-troponin I and hs-troponin T?

BACKGROUND: New highly sensitive (hs) assays have challenged the interpretation of cardiac troponins (cTn). The present study was designed to evaluate simultaneously conventional cTnT and cTnI together with their corresponding highly sensitive determinations in stable hemodialysis (HD) patients. Ability of cTn to stratify HD patient risk was assessed. METHODS: A total of 224 stable HD patients was included in this observational study. cTnT and hs-cTnT were measured using Roche cTnT/hs-cTnT assays based on a Cobas e601® analyzer. cTnI and hs-cTnI were measured using Beckman AccuTnI/hs-TnI IUO assays on Access II system. Patients were followed up prospectively during 9 years. Relationship between cTn level and mortality was assessed through Cox survival analysis. RESULTS: The median cTnT and cTnI concentrations were 38.5 ng/L (IQR, 18.8-76) and 10 ng/L (IQR, 10-20), respectively. The median hs-cTnT and hs-cTnI concentrations were 62.5 ng/L (IQR, 38.8-96.3) and 13.9 ng/L (IQR, 8.4-23.6), respectively. The prevalence of values above the 99th percentile was significantly more marked with cTnT (85.3 and 97.8% for conventional and hs cTnT, respectively) than with cTnI (7.6 and 67.4% for conventional and hs cTnI, respectively). During the follow-up, 167 patients died, mainly from cardiac cause (n=77). The optimized cut-off values, determined by bootstrap method, predicting mortality were 38, 69, 20 and 11 ng/L for cTnT, hs-cTnT, cTnI and hs-cTnI, respectively. After full adjustment, elevated plasma concentrations of all troponin were significant predictors of mortality. CONCLUSIONS: A large proportion of patients free of acute coronary syndrome (ACS) has hs-cTn I or T higher than the 99th percentile which could be seen as a limiting factor for ACS screening. However, all generation and type of troponin assays could be reliable indicators of prognosis risk in HD patients.

Procalcitonin, an Independent Marker of Abdominal Fat Accumulation in Obese Patients.

BACKGROUND: Circulating procalcitonin (PCT) is an inflammatory marker produced by several cell types including adipose tissue following cytokine stimulation. A low-grade inflammation is well recognized in obese patients with insulin resistance but data on PCT levels in obese patients remain scarce. The aim of our study was to evaluate the link between plasma PCT concentration and metabolic parameters of obesity. METHODS: Measurements of biological parameters and total body scan using dual-energy x-ray were performed in all non-diabetic adult patients with a body mass index ≥ 30 kg/m² hospitalized for metabolic and physical assessment of their obesity since January 2010. RESULTS: Elevated plasma PCT levels of the 295 patients included were associated with degree of obesity (OR = 2.76 [1.26-6.03] class III vs. class I obesity), waist circumference (OR = 4.20 [1.98-8.92], highest vs. lowest tercile), and trunk-to-total fat ratio (OR = 6.75 [2.12-21.4], highest vs. lowest tercile). Interestingly, no significant as- sociation between the highest PCT levels and hsCRP (OR = 1.33 [0.68-2.26]) or IR (OR = 1.26 [0.67-2.37]) was found. CONCLUSIONS: Our results showed that plasma PCT levels were independently associated with central adiposity assessed by clinical and imaging assessment, but not with insulin resistance in obese patients.

Osteoprotegerin and sclerostin in chronic kidney disease prior to dialysis: potential partners in vascular calcifications.

BACKGROUND: Osteoprotegerin (OPG), sclerostin and DKK1 constitute opposite bone turnover inhibitors, OPG inhibiting osteoclastogenesis while sclerostin and DKK1 exerting their inhibitory effects on osteoblastogenesis. Both proteins have been recognized as strong risk factors of vascular calcifications in non-dialysis chronic kidney disease (ND-CKD) patients. The aim of this study was to investigate the relationships between these inhibitors and coronary artery calcifications (CAC) in this population. METHODS: A total of 241 ND-CKD patients [143 males; 69.0 (25.0-95.0) years; median estimated glomerular filtration rate using CKD-EPI 35.1 (6.7-120.1) mL/min/1.73 m(2)] were enrolled in this cross-sectional study. All underwent chest multidetector computed tomography for CAC scoring. OPG, sclerostin, DKK1 and mineral metabolism markers including PTH and bone alkaline phosphatase were measured. Logistic regression analyses were used to study the relationships between CAC and these markers. RESULTS: Decline in renal function was associated with a significant increase in OPG and sclerostin while a slight but significant decrease in DKK1 was observed. The main crude associations with presence of CAC were a high level of OPG [OR = 2.55 95% confidence interval (95% CI) (1.35-4.82) for a level ranging from 6.26 to 9.15 pmol/L and OR = 5.74 95% CI (2.87-11.5) for a level ≥9.15 pmol/L; P < 0.0001] and a high level of sclerostin [OR = 2.64 95% CI (1.39-5.00) for a level ranging from 0.748 to 1.139 ng/mL and OR = 3.78 95% CI (1.96-7.31) for a level ≥1.139 ng/mL; P = 0.0002]. A logistic regression model clearly showed that the risk to present CAC was significantly increased when both OPG (≥6.26 pmol/L) and sclerostin (≥0.748 ng/mL) levels were high [crude model: OR = 11.47 95% CI (4.54-29.0); P < 0.0001; model adjusted for age, gender, diabetes, body mass index and smoking habits: OR = 5.69 95% CI (1.76-18.4); P = 0.02]. No association between DKK1 and presence of CAC was observed. CONCLUSIONS: Our results strongly suggest that bone turnover inhibitors, OPG and sclerostin, are independently associated with CAC with potential additive effects in ND-CKD patients.