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Tunneled central venous catheters (CVC) are mainly considered as a rescue vascular access option in dialysis but are still used on approximately one quarter of prevalent patients worldwide even though they are associated with poor performances and higher risks., Study Design: in this retrospective single-center study, we aimed to report on the clinical performances achieved with high-flow tunneled CVCs (DualCath or DCath) and compared them with arteriovenous accesses (AVAs, e.g., AV fistula, AV graft, and Thomas Shunt) in a hospital-based dialysis unit., Methods: Sixty-eight stage 5 chronic kidney disease dialysis-dependent patients (CKD5D) receiving high volume hemodiafiltration were followed-up with for 30 months. The study consisted of two phases: baseline cross-sectional and longitudinal follow-ups of key performance indicators. Clinical performances consisting of effective blood flow and blood volume, recirculation, urea and ionic Kt/V, total Kt, ultrafiltration volume, and percent reduction in β2-M were measured monthly as part of quality control in our unit., Results: At baseline, the effective blood flow using a DCath was close to 400 mL/min, similar to an AVA. Recirculation with a DCath (7%, 6-13%) was higher than with an AVA. The diffusive dialysis dose delivered with a DCath (spKt and eKt/V) and convective dialysis dose achieved with a DCath were slightly lower than those achieved with AVAs, but they were still much higher than is recommended by guidelines. The percent reduction in β2-M achieved with a DCath was also 4 to 10% lower than that achieved with an AVA. On longitudinal follow-up, the main clinical performance indicators of DCaths (total Kt and total ultrafiltration volume, L/session) were maintained as very stable over time and close to those achieved with AVAs., Conclusions: As shown in this study, high-flow DualCath tunneled two-single-lumen silicone catheters may be used to deliver high volume hemodiafiltration in a reliable and consistent manner without compromising clinical performance. These results relied on the specific design of the two silicone cannulas and the strict adherence to best catheter practices.

Introduction: Membranous nephropathy (MN) is the first cause of nephrotic syndrome in patients without diabetes. Its prognosis is variable, and treatment remains controversial because of potential toxicity. Currently, there is no reliable prognostic marker common to all etiologies of MN and routinely available to predict the disease course and guide therapeutic management. Despite the major role of complement in the glomerular damage of MN, its prognostic impact has never been studied. We investigated the frequency and prognostic impact of glomerular deposition of C5b-9 in MN., Methods: We retrospectively selected adults diagnosed with MN (primary or secondary) at Montpellier University Hospital between December 2004 and December 2015. To be included, all patients were required to have complete medical data and a kidney tissue sample for further immunohistochemistry. We performed PLA2R1 , C4d, and C5b-9 staining by immunohistochemistry., Results: Sixty-four adults were included: 45 with primary MN and 19 with secondary MN. C4d was positive in the glomeruli of 61 adults (95.3%). Twenty-nine adults (45.3%) had glomerular deposition of C5b-9. Patients with glomerular deposition of C5b-9 had more severe nephrotic syndrome on diagnosis and lower remission and renal survival rates than adults without., Conclusion: C5b-9 glomerular staining is a powerful and easily accessible tool for stratifying adults according to their renal prognosis. The efficacy of complement inhibitors should be tested in adults with glomerular deposition of C5b-9., (© 2022 Published by Elsevier Inc. on behalf of the International Society of Nephrology.)

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 V Watson , V MF-BIA , and V OCM 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 V Watson , V MF-BIA , and V OCM 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., (© 2021 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

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.

Heart failure is the most frequent cardiac complication of chronic kidney disease (CKD). Biomarkers help identify high-risk patients. Natriuretic peptides (BNP and NT-proBNP) are largely used for monitoring patients with cardiac failure but are highly dependent on glomerular filtration rate (GFR). Soluble suppression of tumorigenicity 2 (sST2) biomarker is well identified in risk stratification of cardiovascular (CV) events in heart failure. Furthermore, sST2 is included in a bioclinical score to stratify mortality risk. The aims of this study were to evaluate (i) the interest of circulating sST2 level in heart dysfunction and (ii) the bioclinical score (Barcelona Bio-Heart Failure risk calculator) to predict the risk of composite outcome (major adverse coronary events) and mortality in the CKD population. A retrospective study was carried out on 218 CKD patients enrolled from 2004 to 2015 at Montpellier University Hospital. sST2 was measured by ELISA (Presage ST2® kit). GFR was estimated by the CKD-EPI equation (eGFR). Indices of cardiac parameters were performed by cardiac echography. No patient had reduced ejection fraction. 112 patients had left ventricular hypertrophy, and 184 presented cardiac dysfunction, with structural, functional abnormalities or both. sST2 was independent of age and eGFR ( ρ = 0.05, p = 0.44, and ρ = -0.07, p = 0.3, respectively). Regarding echocardiogram data, sST2 was correlated with left ventricular mass index ( ρ = 0.16, p = 0.02), left atrial diameter ( ρ = 0.14, p = 0.04), and volume index ( ρ = 0.13, p = 0.05). sST2 alone did not change risk prediction of death and/or CV events compared to natriuretic peptides. Included in the Barcelona Bio-Heart Failure (BCN Bio-HF) score, sST2 added value and better stratified the risk of CV events and/or death in CKD patients ( p < 0.0001). To conclude, sST2 was associated with cardiac remodeling independently of eGFR, unlike other cardiac biomarkers. Added to the BCN Bio-HF score, the risk stratification of death and/or CV events in nondialyzed CKD patients was highly improved.

Background: Muscle weakness is associated with increased mortality risk in chronic haemodialysis (CHD) patients. Protein energy wasting (PEW) and low physical activity could impair muscle quality and contribute to muscle weakness beyond muscle wasting in these patients. Aim of this study was to assess clinical and biological parameters involved in the reduction of muscle strength of CHD patients., Methods: One hundred and twenty-three CHD patients (80 males, 43 females; 68,8 [57.9-78.8] y.o.) were included in this study. Maximal voluntary force (MVF) of quadriceps was assessed using a belt-stabilized hand-held dynamometer. Muscle quality was evaluated by muscle specific torque, defined as the strength per unit of muscle mass. Muscle mass was estimated using lean tissue index (LTI), skeletal muscle mass (SMM) assessed by bioelectrical impedance analysis and creatinine index (CI). Voorrips questionnaire was used to estimate physical activity. Criteria for the diagnosis of PEW were serum albumin, body mass index < 23 kg/m2, creatinine index < 18.82 mg/kg/d and low dietary protein intake estimated by nPCR < 0.80g/kg/d., Results: MVF was 76.1 [58.2-111.7] N.m. and was associated with CI (β = 5.3 [2.2-8.4], p = 0.001), LTI (β = 2.8 [0.6-5.1], p = 0.013), Voorrips score (β = 17.4 [2.9-31.9], p = 0.02) and serum albumin (β = 1.9 [0.5-3.2], p = 0.006). Only serum albumin (β = 0.09 [0.03-0.15], p = 0.003), Voorrips score (β = 0.8 [0.2-1.5], p = 0.005) and CI (β = 0.2 [0.1-0.3], p<0.001) remained associated with muscle specific torque. Thirty patients have dynapenia defined as impaired MVF with maintained SMM and were younger with high hs-CRP (p = 0.001), PEW criteria (p<0.001) and low Voorrips score (p = 0.001), and reduced dialysis vintage (p<0.046)., Conclusions: Beyond atrophy, physical inactivity and PEW conspire to impair muscle strength and specific torque in CHD patients and could be related to muscle quality., Trial Registration: ClinicalTrials.gov NCT02806089., Competing Interests: The authors have declared that no competing interests exist.

Large cohort studies suggest that high convective volumes associated with online hemodiafiltration may reduce the risk of mortality/morbidity compared to optimal high-flux hemodialysis. By contrast, intradialytic tolerance is not well studied. The aim of the FRENCHIE (French Convective versus Hemodialysis in Elderly) study was to compare high-flux hemodialysis and online hemodiafiltration in terms of intradialytic tolerance. In this prospective, open-label randomized controlled trial, 381 elderly chronic hemodialysis patients (over age 65) were randomly assigned in a one-to-one ratio to either high-flux hemodialysis or online hemodiafiltration. The primary outcome was intradialytic tolerance (day 30-day 120). Secondary outcomes included health-related quality of life, cardiovascular risk biomarkers, morbidity, and mortality. During the observational period for intradialytic tolerance, 85% and 84% of patients in high-flux hemodialysis and online hemodiafiltration arms, respectively, experienced at least one adverse event without significant difference between groups. As exploratory analysis, intradialytic tolerance was also studied, considering the sessions as a statistical unit according to treatment actually received. Over a total of 11,981 sessions, 2,935 were complicated by the occurrence of at least one adverse event, with a significantly lower occurrence in online hemodiafiltration with fewer episodes of intradialytic symptomatic hypotension and muscle cramps. By contrast, health-related quality of life, morbidity, and mortality were not different in both groups. An improvement in the control of metabolic bone disease biomarkers and β2-microglobulin level without change in serum albumin concentration was observed with online hemodiafiltration. Thus, overall outcomes favor online hemodiafiltration over high-flux hemodialysis in the elderly., (Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Objectives: In hemodialysis, diminution of muscle strength constitutes a major prognostic factor of mortality. Currently, measurement of quadriceps isometric maximal voluntary force (MVF) represents the reference method to investigate muscle strength. However, reduction of MVF is rarely detected in these patients due to the absence of portative bedside tools in clinical practice. The purposes of this study were therefore to assess the agreement of a belt-stabilized handheld dynamometer (HHD) with the dynamometer chair (reference method) and to determine intratester and intertester reliability of the quadriceps MVF measurements using belt-stabilized HHD in healthy subjects and in hemodialysis patients., Design: Repeated-measures cross-sectional study., Setting: Clinical and academic hospital., Participants: Fifty-three healthy adult subjects (23 males, 36.5 + 12.5 y.o.) and 21 hemodialysis patients (14 males, 72.4 + 13.3 y.o., dialysis vintage 30 + 75.1 months)., Intervention: Not applicable., Main Outcome Measure: MVF measurements were assessed with belt-stabilized HHD and dynamometer chair, by two independent investigators. The agreement between the two devices would be quantified using the Bland-Altman 95% limits of agreement (LOA) method and the Spearman correlation., Results: For healthy subjects and hemodialysis patients, Spearman coefficients between belt-stabilized HHD and dynamometer chair were 0.63 and 0.75, respectively (P < .05). In hemodialysis group, reliability was excellent for both the intratester and intertester reliability R 2  = 0.85 (P < .01) and R 2  = 0.90 (P < .01), respectively. In all individuals, the mean difference between the dynamometer chair and the belt-stabilized HHD was -13.07 ± 21.77 N.m. (P < .001). The LOA for the upper and the lower was 29.59 and -55.73 N.m., respectively., Conclusion: In healthy subjects and in hemodialysis patients, the belt-stabilized HHD dynamometer appears as a valid and reliable method to measure in clinical practice isometric MVF of quadriceps in hemodialysis patients. Therefore, the belt-stabilized HHD appears as a suitable and a relevant diagnostic tool for the identification of muscle dysfunction in hemodialysis patients., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The association between proprotein convertase subtilisin/kexin type 9 (PCSK9), a critical regulator of low-density lipoprotein (LDL) metabolism, and kidney function is a matter of debate., Objective: We aimed to assess the association of circulating PCSK9 concentrations with both glomerular filtration rate (eGFR) and serum lipid parameters in nondiabetic patients with chronic kidney disease (CKD)., Methods: Fasting plasma PCSK9 concentrations were measured by ELISA in 94 nondiabetic nondialysis CKD (ND-CKD) patients not receiving statins, at different stages of CKD., Results: Plasma PCSK9 levels were associated neither to eGFR (P = .770) nor to proteinuria (P = .888) at several stages of CKD. In addition, plasma PCSK9 levels did not vary significantly between the different CKD stages. Plasma PCSK9 concentrations were positively correlated with apolipoprotein B (r = 0.221; P = .03) and triglycerides (r = 0.211; P = .04) but not with total cholesterol, calculated LDL-cholesterol, HDL cholesterol, lipoprotein(a), or CRP., Conclusion: In a homogeneous population of nondiabetic subjects without lipid-lowering therapy, plasma PCSK9 concentrations are not associated to eGFR at several stages of CKD. These data suggest that kidney function per se does not impact significantly PCSK9 metabolism., (Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

New highly sensitive (hs) assays have challenged the interpretation of cardiac troponins (cTn) as markers of injury while natriuretic peptides remain the markers of choice for myocardial dysfunction. However, variability extracardiac factors such as age, gender and renal function may alter circulating levels. In chronic kidney disease (CKD), the increase in circulating levels of these biomarkers in the absence of cardiac disease underlines the problem of discriminative value for diagnosis as well as the need to redefine the thresholds. In addition, these biomarkers are of potential interest to stratify cardiovascular risk, the leading cause of death in CKD. The aim of this work is to clarify the effect of age and renal function on circulating levels of high-sensitivity troponins and natriuretic peptides.

Background/aims: Serum free light chain (FLC) levels are correlated with chronic kidney disease (CKD) stages and are highest in patients on hemodialysis (HD). Aim of this study was to assess the FLC removal efficiency of Elisio™-210H dialyzer using either high-flux HD or on line high efficiency hemodiafiltration (HDF) modalities in CKD-5D patients., Methods: In this prospective and comparative study, 20 CKD-5D patients free from multiple myeloma were randomized in two groups: HD versus on line HDF. All patients were dialyzed with Elisio™-210H dialyzer. Serum samples were collected before and after the midweek dialysis session, before randomization and at the end of the study to measure κ and λ FLC concentrations. Reduction ratios were corrected for net ultrafiltration., Results: For both HD and HDF mode, κ and λ FLC concentrations were significantly lower after dialysis than before but median reductions in κ and λ FLC levels were significantly higher in HDF versus HD groups (κ 73.5 vs. 65.5 %, p = 0.04 and λ 51.0 vs. 36.6 %, p = 0.07). After dialysis, all κ/λ ratio values were between 0.26 and 1.65 which is the reference range described in subjects with normal kidney function, for both HD and HDF groups (median κ/λ ratios were 0.80 [0.47-1.22] and 0.67 [0.50-0.79] respectively)., Conclusion: This study shows the superiority of on line HDF compared with HD to remove both κ and λ FLC. Moreover, all post-dialysis κ/λ ratios reached normal reference range.

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., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: The number of circulating endothelial progenitor cells (EPCs) decreases on account of chronic kidney disease (CKD)., Methods: Twenty patients were enrolled in this prospective and randomised study in two parallel arms: conventional haemodialysis versus online haemodiafiltration. EPCs number and T-cell activation were analysed at baseline and monthly during a 4-month period of follow-up., Results: CD38(bright) and HLA-DR+ expression among CD8 memory T cells were negatively associated with both CD34+ (r = -0.70, p = 0.0006) and CD34+ CD133+ (r = -0.62, p = 0.004) cell numbers. Conversely, a positive correlation was observed between CD34+ and CD34+ CD133+ cells with transferrin (r = 0.75, p = 0.0001 and r = 0.47, p = 0.04, respectively), and CD34+ CD133+ cells with transthyretin (r = 0.51, p = 0.02). No significant association was observed between dialysis modality and the evolution of the EPC number., Conclusions: Chronic T-cell activation may be a component of the malnutrition inflammation complex syndrome that adversely influences EPC mobilization in CKD patients., (© 2015 S. Karger AG, Basel.)

Background and Objectives: Protein-energy wasting is common in long-term haemodialysis (HD) patients with chronic kidney disease and is associated with increased morbidity and mortality. The creatinine index (CI) is a simple and useful nutritional parameter reflecting the dietary skeletal muscle protein intake and skeletal muscle mass of the patient. Because of the complexity of creatinine kinetic modeling (CKM) to derive CI, we developed a more simplified formula to estimate CI in HD patients., Design, Setting, Participants & Measurements: A large database of 549 HD patients followed over more than 20 years including monthly CKM-derived CI values was used to develop a simple equation based on patient demographics, predialysis serum creatinine values and dialysis dose (spKt/V) using mixed regression models., Results: The equation to estimate CI was developed based on age, gender, pre-dialysis serum creatinine concentrations and spKt/V urea. The equation-derived CI correlated strongly with the measured CI using CKM (correlation coefficient  = 0.79, p-value <0.001). The mean error of CI prediction using the equation was 13.47%. Preliminary examples of few typical HD patients have been used to illustrate the clinical relevance and potential usefulness of CI., Conclusions: The elementary equation used to derive CI using demographic parameters, pre-dialysis serum creatinine concentrations and dialysis dose is a simple and accurate surrogate measure for muscle mass estimation. However, the predictive value of the simplified CI assessment method on mortality deserves further evaluation in large cohorts of HD patients.

Complex interactions existing between cardiac and renal diseases led to define 5 types of so-called cardiorenal syndromes. This classification is based on the organ primarily involved and the acute or chronic failure. The mutual impact of renal and cardiac functions makes it difficult to evaluate and manage patients with cardiorenal syndromes and worsen morbidity and mortality. This review seeks to discuss the place of biomarkers in diagnosis, management and follow-up of patients with cardiorenal syndromes. Biomarkers can be classified as functional (creatinine, cystatin C…) or lesional (neutrophil gelatinase-associated lipocalin, urinary cystatin C…) renal markers and functional (natriuretic peptides…) or lesional (troponin, fatty acid binding protein) cardiac markers. A last kind of biomarkers reflects the dialogue between heart and kidney (renin-angiotensin-aldosteron-system, indicators of activation of arginine vasopressin system) or the systemic impact (inflammation, oxidative stress…). In order to evaluate accurately the complex interactions that are the basis of cardiorenal syndromes, a multi-marker approach seems nowadays necessary.

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.

The safety of online hemodiafiltration (ol-HDF) relies on very strict rules of use. The use of ultrapure water to feed an ol-HDF machine is a basic requirement for ol-HDF. Technical aspects and microbial monitoring have been precisely described in the European Best Practice Guidelines. Specifically designed and certified ol-HDF machines are needed. All these machines share the production of substitution fluid by the cold sterilization process of fresh dialysate based on ultrafilters. Hygiene handling is a crucial measure to ensure permanent safety of the ol-HDF system. Frequent disinfection of the water treatment system and dialysis machine, destruction of biofilm by chemical agents and/or thermochemical disinfection, change of filters at regular intervals, and maintenance of a permanent circulation of water are among the basic measures required to ensure ultra-purity of water and dialysis fluid. Optimal performances of ol-HDF require the use of high blood flow (300-400 ml/min), highly permeable and adequately sized hemodiafilters, a high volume of substitution (5-6 l/h) and high dialysate flow (500 ml/min). The site and type of substitution (pre-, post-, mixed, and mid-dilution) should be customized to each patient according to its blood hemorheology and its filtration fraction limitation (transmembrane pressure). All attempts should be made to maximize the fluid volume exchange per session (convective dose) in any cases. The treatment schedule in terms of session duration and weekly frequency need to be adjusted individually to improve hemodynamic tolerance, to facilitate correction of fluid overload and to increase dialysis dose (for middle-sized solutes) in order to reduce circulating levels of major uremic toxins. ol-HDF is the more advanced form of renal replacement therapy offering high efficiency over a large spectrum of toxins, high biocompatibility profile and high flexible modality. ol-HDF may help to improve global care of chronic kidney disease patients and may be considered the renal replacement therapy of the future., (Copyright © 2011 S. Karger AG, Basel.)

Whole-blood viscosity is increasingly being recognized as a factor implicated in the vascular disease progression in high-risk chronic kidney disease patients. Intermittent hemodialysis and hemodiafiltration sessions, characterized by rapid volume changes and anemia correction by erythropoietin stimulating agents, are favorable conditions for enhancing whole-blood viscosity changes and consequently triggering cardiovascular events. To evaluate whole-blood viscosity changes induced by hemodiafiltration, a cross-sectional study has been performed in a group of 28 stable patients. In order to assess the impact of vessel size on whole-blood viscosity changes, we performed a dynamic whole viscosity analysis on a wide spectrum of shear rates reproducing vasculature hemorheologic conditions. Blood viscosity changes are dependent on patient characteristics, hemoglobin, and total plasma protein concentrations. Whole blood viscosity increases significantly during hemodiafiltration over the complete spectrum of shear rates. Dynamic whole-blood viscosity (WBV) increases up to 60%, predominantly at low shear rates in small arterioles and capillary beds. This observation underlines the potential pathogenic contribution of WBV increase in capillaries triggering cardiovascular events in the postdialysis period. Eight patients died from cardiovascular events. Higher WBV increase was noted in this group but did not reach statistical significance due to the insufficient power of the study. Hemorheological changes associated with WBV increase in capillary beds may contribute to aggravate silent tissue hypoxemia and precipitate cardiovascular events in chronic kidney disease patients. Prospective studies specifically designed and powered to evaluate the impact of WBV changes on cardiovascular events in dialysis patients are required., (© 2010 The Authors. Hemodialysis International © 2010 International Society for Hemodialysis.)

Background: The accumulation of larger and protein-bound toxins is involved in the uraemic syndrome but their elimination by dialysis therapy remains difficult. In the present study, the impact of the albumin permeability of recently introduced advanced high-flux dialysis membranes on the removal of such substances was tested in haemodialysis and online post-dilution haemodiafiltration., Methods: Two types of polyethersulfone membranes only differing in albumin permeability (referred as PU- and PU+) were compared in eight patients on maintenance dialysis in a prospective cross-over manner. Treatment settings were identical for individual patients: time 229 +/- 22 min; blood flow rate 378 +/- 33 mL/min; dialysate flow rate 500 mL/min; substitution flow rate in haemodiafiltration 94 +/- 9 mL/min. Removal of the protein-bound compounds p-cresyl sulfate (pCS) and indoxyl sulfate (IS) was determined by reduction ratios (RRs), dialytic clearances and mass in continuously collected dialysate. In addition, the elimination of the low-molecular weight (LMW) proteins beta(2)-microglobulin, cystatin c, myoglobin (myo), free retinol-binding protein (rbp) and albumin was measured., Results: Plasma levels of the protein-bound toxins were significantly decreased by all treatment forms. However, the decreases were comparable between dialysis membranes and between haemodialysis and haemodiafiltration. The RRs of total pCS ranged between 40.4 +/- 25.3 and 47.8 +/- 10.3% and of total IS between 50.4 +/- 2.6 and 54.6 +/- 8.7%. Elimination of free protein-bound toxins as assessed by their mass in dialysate closely correlated positively with the pre-treatment plasma concentrations being r = 0.920 (P < 0.001) for total pCS and r = 0.906 (P < 0.001) for total IS, respectively. Compared to haemodialysis, much higher removal of all LMW proteins was found in haemodiafiltration. Dialysis membrane differences were only obvious in haemodialysis for the larger LMW proteins myo and rbp yielding significantly higher RRs for PU+ (myo 46 +/- 9 versus 37 +/- 9%; rbp 18 +/- 5 versus 15 +/- 5%; P < 0.05). Additionally, the albumin loss varied between membranes and treatment modes being undetectable with PU- in haemodialysis and highest with PU+ in haemodiafiltration (1430 +/- 566 mg)., Conclusions: The elimination of protein-bound compounds into dialysate is predicted by the level of pre-treatment plasma concentrations and depends particularly on diffusion. Lacking enhanced removal in online post-dilution haemodiafiltration emphasizes the minor significance of convection for the clearance of these solutes. Compared to LMW proteins, the highly protein-bound toxins pCS and IS are less effectively eliminated with all treatment forms. For a sustained decrease of pCS and IS plasma levels, alternative strategies promise to be more efficient therapy forms.

Bed-side formulae established from urea kinetic modelling offers a simple and convenient tool to determine the protein catabolic rate (PCR) and its equivalent the dietary protein intake (DPI), in hemodialysis patients, two major parameters used for assessing the dialysis dose adequacy and its protein nutritional consequences. Simplified urea kinetic analysis, must be part of the permanent quality control of the hemodialysis patient. These formulae contribute to judge more objectively the efficacy of renal replacement therapy program delivered to hemodialysis patients. Indeed, these formulae may not substitute to the clinical judgment of physician and may not replace conventional and major dialysis adequacy indicators (blood pressure control, extracellular and blood pressure control, bone and mineral metabolism control, anemia correction) or nutritional status (anthropometric data, somatic proteins, subjective global assessment...) By providing a way of assessing "dose of dialysis delivered" and "dietary protein intake", bed-side formulae derived from urea kinetic modelling offer a convenient and cheap means of quantifying dialysis adequacy. These formulae bring to the Physician a necessary although not sufficient complementary tool for assessing dialysis adequacy in hemodialysis patient.

Background: Infection constitutes a leading cause of morbidity and mortality in hemodialysis (HD) patients. The type of vascular access is an important determinant of the risk of infection. Therefore, identification of risk factors leading to catheter-related bacteremia (CRB) is strongly required. The aim of this prospective large cohort study of HD patients using only catheters as vascular access was to isolate risk factors for CRB., Methods: 2,230 permanent silicone dual catheters implanted in 1,749 patients between November 1982 and November 2005 were studied. The following data were collected at the time of catheter implantation: presence of hypertension, diabetes mellitus, obesity, atherosclerosis, immunodepression, Wright-Khan index, site and side of catheter insertion, and history of bacteremia., Results: The site of catheter insertion was internal jugular (n = 2,133), subclavian (n = 79) and femoral (n = 17). Duration of catheter use was as follows: 30-90 days (n = 1,607) and >90 days (n = 1,054); 226 episodes of bacteremia occurred in 197 catheters. Microorganisms responsible were mainly Staphylococcus aureus, coagulase-negative staphylococci, Enterobacter spp. and Pseudomonas aeruginosa. The overall incidence of bacteremic episodes was 0.514/1,000 catheter days. Hypertension, atherosclerosis, diabetes mellitus, site of catheter implantation, duration of catheter use, Wright-Khan comorbidity index and previous history of CRB were significant risk factors associated with bacteremia in univariate analysis. Multivariate analysis revealed that a previous history of a bacteremic episode (odds ratio, OR = 2.70, 95% confidence interval, CI = 1.56-4.68), diabetes mellitus (OR = 2.37, 95% CI = 1.65-3.39), duration of catheter use >90 days (OR = 1.85, 95% CI = 1.35-2.55) and hypertension (OR = 1.49, 95% CI = 1.08-2.04) were still significant factors associated with bacteremia., Conclusion: Reducing CRB is still a challenge for nephrologists to reduce patient morbidity and mortality. Our study could demonstrate that diabetes, previous history of CRB, site of catheter implantation and duration of catheter use were the most important risk factors for bacteremia. Therefore, to prevent CRB, particular attention should be paid to patients with diabetes and a previous history of bacteremia following strict hygienic and aseptic rules for catheter handling associated with the regular use of antiseptic lock solutions., ((c) 2009 S. Karger AG, Basel.)

Correcting the renal anemia in dialysis patient require the optimal management of the erythropoietic stimulating agents (ESA) available on the market. In other words, that means that the prescription of these agents should be performed according to the specific pharmacokinetic and pharmacodynamic profiles of these agents. Two major classes of ESA are presently available for clinicians: one being considered as short acting substances (epoetine alfa and Epoetine Beta); the other one being considered as long acting substances (darbepoetin alfa). Several other agents are being currently evaluated or waiting for approval. For the short acting ESA, subcutaneous administration has been proved able to reduce weekly needs by 20 to 30% for the same efficacy, while the optimal frequency dosing being once and twice per week. For long acting ESA, the beneficial effect of the subcutaneous administration tend to disappear in hemodialysis patient, while the optimal frequency dosing being once a week to once every two week. These treatment schedules of prescription must be adapted according to the dialysis modality (hemodialysis, peritoneal dialysis) and the basal needs for ESA. The efficiency of ESA is also conditioned by the dialysis quality and efficiency, the iron repletion state, the blood losses and the presence of resistance factors. The optimal management of anemia in dialysis patient relies on an optimized dosing of ESA, a reduction of blood losses and a suppression of resistance factors to ESA action.

Residual renal function (RRF) contributes to the achievement of treatment adequacy in stage 5 chronic kidney disease (CKD-5) patients. It may facilitate patients' acceptance of renal replacement therapy (RRT) in allowing reduction of treatment time duration and minimising dietary and fluid restriction. It has been confirmed to improve dialysis patient outcomes. Attempts to preserve RRF in incident Stage 5 chronic kidney disease patients are still subject to intense controversies in the nephrology community. The aim of this review is to analyse the role of renal replacement modalities in the maintenance of RRF in dialysis patients. Under the scope of this manuscript, four questions are explored: Is the preservation of residual renal function an objective for dialysis adequacy? Does dialysis modality affect the decline of RRF? What are the factors implicated by this loss of RRF? At what expense can the maintenance of RRF be achieved in dialysis patients? Preservation of RRF is undoubtedly an interesting means to enhance the efficacy of renal replacement therapy and reduce dietary fluid restriction but it should not be considered as a goal of dialysis adequacy in dialysis patients. Further, preservation of RRF must be considered as a permanent trade-off between patient comfort and chronic fluid volume overload.