Serum osteoprotegerin is associated with pulse pressure in kidney transplant recipients

Pulse pressure (PP) reflects increased large artery stiffness, which is caused, in part, by arterial calcification in patients with chronic kidney disease. PP has been shown to predict both cardiovascular and cerebrovascular events in various patient populations, including kidney transplant (KTX) recipients. Osteoprotegerin (OPG) is a marker and regulator of arterial calcification, and it is related to cardiovascular survival in hemodialysis patients. Here we tested the hypothesis that OPG is associated with increased pulse pressure. We cross-sectionally analyzed the association between serum OPG and PP in a prevalent cohort of 969 KTX patients (mean age: 51 +/- 13 years, 57% male, 21% diabetics, mean eGFR 51 +/- 20 ml/min/1.73 m2). Independent associations were tested in a linear regression model adjusted for multiple covariables. PP was positively correlated with serum OPG (rho = 0.284, p < 0.001). Additionally, a positive correlation was seen between PP versus age (r = 0.358, p < 0.001), the Charlson Comorbidity Index (r = 0.232, p < 0.001), serum glucose (r = 0.172, p < 0.001), BMI (r = 0.133, p = 0.001) and serum cholesterol (r = 0.094, p = 0.003). PP was negatively correlated with serum Ca, albumin and eGFR. The association between PP and OPG remained significant after adjusting for multiple potentially relevant covariables (beta = 0.143, p < 0.001). We conclude that serum OPG is independently associated with pulse pressure in kidney transplant recipients

Bone Biomarkers Help Grading Severity of Coronary Calcifications in Non Dialysis Chronic Kidney Disease Patients

BACKGROUND: Osteoprotegerin (OPG) and fibroblast growth factor-23 (FGF23) are 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 FGF23, OPG, and coronary artery calcifications (CAC) in this population and to attempt identification of the most powerful biomarker of CAC: FGF23? OPG? METHODOLOGY/PRINCIPAL FINDINGS: 195 ND-CKD patients (112 males/83 females, 70.8 [27.4-94.6] years) were enrolled in this cross-sectional study. All underwent chest multidetector computed tomography for CAC scoring. Vascular risk markers including FGF23 and OPG were measured. Logistic regression analyses were used to study the potential relationships between CAC and these markers. The fully adjusted-univariate analysis clearly showed high OPG (≥10.71 pmol/L) as the only variable significantly associated with moderate CAC ([100-400[) (OR = 2.73 [1.03;7.26]; p = 0.04). Such association failed to persist for CAC scoring higher than 400. Indeed, severe CAC was only associated with high phosphate fractional excretion (FEPO(4)) (≥38.71%) (OR = 5.47 [1.76;17.0]; p = 0.003) and high FGF23 (≥173.30 RU/mL) (OR = 5.40 [1.91;15.3]; p = 0.002). In addition, the risk to present severe CAC when FGF23 level was high was not significantly different when OPG was normal or high. Conversely, the risk to present moderate CAC when OPG level was high was not significantly different when FGF23 was normal or high. CONCLUSIONS: Our results strongly suggest that OPG is associated to moderate CAC while FGF23 rather represents a biomarker of severe CAC in ND-CKD patients

State of the art of immunoassay methods for B-type natriuretic peptides: An update

The aim of this review article is to give an update on the state of the art of the immunoassay methods for the measurement of B-type natriuretic peptide (BNP) and its related peptides. Using chromatographic procedures, several studies reported an increasing number of circulating peptides related to BNP in human plasma of patients with heart failure. These peptides may have reduced or even no biological activity. Furthermore, other studies have suggested that, using immunoassays that are considered specific for BNP, the precursor of the peptide hormone, proBNP, constitutes a major portion of the peptide measured in plasma of patients with heart failure. Because BNP immunoassay methods show large (up to 50%) systematic differences in values, the use of identical decision values for all immunoassay methods, as suggested by the most recent international guidelines, seems unreasonable. Since proBNP significantly cross-reacts with all commercial immunoassay methods considered specific for BNP, manufacturers should test and clearly declare the degree of cross-reactivity of glycosylated and non-glycosylated proBNP in their BNP immunoassay methods. Clinicians should take into account that there are large systematic differences between methods when they compare results from different laboratories that use different BNP immunoassays. On the other hand, clinical laboratories should take part in external quality assessment (EQA) programs to evaluate the bias of their method in comparison to other BNP methods. Finally, the authors believe that the development of more specific methods for the active peptide, BNP1–32, should reduce the systematic differences between methods and result in better harmonization of results

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

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. 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. 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). The introduction of a new PTH assay generation in clinical practice should be carried out with caution. © 2018 Walter de Gruyter GmbH, Berlin/Boston

Cystatin C is a reliable marker for estimation of glomerular filtration rate in renal transplantation: validation of a new turbidimetric assay using monospecific sheep antibodies

Background: The potential use of Cystatin C was recently assessed in kidney transplantation. A new particle-enhanced turbidimetric immunoassay (PETIA) that uses sheep antibodies (Binding Site Human Cystatin C immunoassay) has been developed. Analytical performance of this new assay was evaluated. Clinical relevance was determined by comparison with a reference method in a cohort of kidney transplant patients. Patients and methods: First, the analytical performance of the Binding Site cystatin C kit was tested on SPAPLUS® and Hitachi® analyzers. Second, a comparison study was performed using SPAPLUS® analyzer against two other cystatin C methods (the Siemens-PENIA method on BNII® and the Dako-PETIA application on Olympus AU640®). Third, the glomerular filtration rate (GFR) was estimated using several predictive cystatin C- and creatinine-based equations and compared to GFR measured by an isotopic method (99mTc-DTPA). These predictive algorithms were analyzed with respect to bias, precision and accuracy. Results: Total intra-assay and inter-assay coefficients of variation were below 5%. Values obtained with the SPAPLUS® correlated with the Siemens-PENIA and the Dako-PETIA methods. The creatinine and cystatin C-based equation allowed reliable assessment of GFR in our population of renal transplantation. Conclusions: The use of algorithms based on cystatin C and creatinine could provide a reliable estimate of GFR in kidney transplantation

Long term reference change value of creatinine in HIV-positive patients with anti-retroviral therapy: A new tool in clinical practice

International audienc

Sclerostin: a new biomarker of interest in nephrology

Sclerostin is an osteocyte-specific glycoprotein secreted by the osteocyte and involved in the regulation of bone mass. High sclerostin levels are associated with osteoporosis, whereas low sclerostin levels are correlated with higher bone mineral density. It seems interesting to investigate a potential association between sclerostin levels and vascular calcifications since sclerostin is considered as a potent inhibitor of bone formation. In chronic kidney disease, serum sclerostin levels rise as renal function declines. Preliminary studies show a positive association between serum sclerostin and vascular calcification, but the link between sclerostin and survival of patients remains unclear in the absence of large-scale studies