Comparative Clinical Performances of Tunneled Central Venous Catheters versus Arterio-Venous Accesses in Patients Receiving High-Volume Hemodiafiltration: The Case for High-Flow DualCath, a Tunneled Two-Single-Lumen Silicone Catheter.

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 ß2-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 ß2-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.

C5b-9 Glomerular Deposits Are Associated With Poor Renal Survival in Membranous Nephropathy.

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.

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.

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.

sST2 as a New Biomarker of Chronic Kidney Disease-Induced Cardiac Remodeling: Impact on Risk Prediction.

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.

Physical inactivity and protein energy wasting play independent roles in muscle weakness in maintenance haemodialysis patients.

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 (ß = 5.3 [2.2-8.4], p = 0.001), LTI (ß = 2.8 [0.6-5.1], p = 0.013), Voorrips score (ß = 17.4 [2.9-31.9], p = 0.02) and serum albumin (ß = 1.9 [0.5-3.2], p = 0.006). Only serum albumin (ß = 0.09 [0.03-0.15], p = 0.003), Voorrips score (ß = 0.8 [0.2-1.5], p = 0.005) and CI (ß = 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.

[Online hemodiafiltration: Practical aspects, safety and efficacy]. / Hémodiafiltration en ligne : modalités pratiques, sécurité et efficacité de la méthode.

Purification of high molecular uremic toxins by conventional hemodialysis is limited. It remains associated with a high morbidity and excessively high mortality. Online hemodiafiltration using a high permeability hemodiafilter, an ultrapure dialysate, and which tends to maximize substitution volumes, provides a high efficiency and low bio-incompatibility renal supplementation. Regular use of online hemodiafiltration is associated with reduced morbidity (reduction of intradialytic hypotension episodes, improved blood pressure control, reduced inflammatory profile, better anemia correction and prevention of ß2-microglobulin-associated amyloidosis). Recently, several cohort studies have shown that hemodiafiltration with high substitution volume was associated with a significant reduction in mortality. Randomized studies have been conducted in Europe to confirm these facts. The high safety of online hemodiafiltration has been confirmed in clinical practice by prospective studies. Online hemodiafiltration has reached its full maturity phase and is expected to represent the new standard of renal replacement therapy.

Plasma PCSK9 concentrations during the course of nondiabetic chronic kidney disease: Relationship with glomerular filtration rate and lipid metabolism.

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.

Standardized Method to Measure Muscle Force at the Bedside in Hemodialysis Patients.

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 R2 = 0.85 (P < .01) and R2 = 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.

Treatment tolerance and patient-reported outcomes favor online hemodiafiltration compared to high-flux hemodialysis in the elderly.

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 ß2-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.

How to interpret cardiac biomarkers in renal failure and elderly?

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.

Hemodiafiltration improves free light chain removal and normalizes κ/λ ratio in hemodialysis patients.

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.

T-Cell Activation and Malnutrition Adversely Impact on Endothelial Progenitor Cell Mobilization in Patients on Extracorporeal Maintenance Dialysis Therapy.

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.

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.

Creatinine index as a surrogate of lean body mass derived from urea Kt/V, pre-dialysis serum levels and anthropometric characteristics of haemodialysis patients.

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.

[Biomarkers of cardiorenal syndrome]. / Biomarqueurs du syndrome cardiorénal.

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.

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.

Spontaneous renal artery dissection with renal infarction.

Spontaneous renal artery dissection (SRAD) is a rare entity, which often presents diagnostic difficulties because of its non-specific clinical presentation. We report six cases complicated with renal infarction, occurring in middle-aged male patients without risk factors, illustrating the difficulty and delay for diagnosing SRAD. Ultrasound and Doppler imaging were not sensitive enough to confirm the diagnosis, and contrast-enhanced abdominal computed tomography was used to correct the diagnosis and allow the clinicians to propose appropriate treatment. We conclude that considering the urgency in diagnosing and treating SRAD, contrast enhanced abdominal tomography and/or abdominal magnetic resonance imaging should be proposed as soon as a suspicion of SRAD is evoked by the clinical presentation.

Online high-efficiency haemodiafiltration achieves higher serum free light chain removal than high-flux haemodialysis in multiple myeloma patients: preliminary quantitative study.

BACKGROUND: Fast reduction of serum free light chain (FLC) levels correlate with renal recovery in cast nephropathy. Because convection has the capacity to remove proteins of higher molecular weights, we hypothesized that haemodiafiltration (HDF) would be superior to haemodialysis (HD) for FLC clearance. METHODS: We retrospectively identified all renal replacement therapy (RRT) sessions performed in multiple myeloma patients with pre- and post-treatment FLC measurements during a 2-year period. Using kinetic modelling, we calculated reduction percentages corrected for net ultrafiltration, effective clearances, net mass removal and Kt/V for both kappa (κ) and lambda (λ) serum FLC. RESULTS: We analysed 27 (10 HD and 17 HDF) RRT sessions realized in a total of six subjects. HDF resulted in higher FLC removal rates when compared to HD. Moreover, high-efficiency (i.e. substitution volume > 15 L/session) HDF demonstrated median efficient FLC clearances roughly twice superior to high-flux HD for both κ (59.0 versus 33.8 mL/min, respectively; P < 0.01) and λ (40.5 versus 19.7 mL/min, respectively; P = 0.02) FLC. In post-dilution HDF treatments, corrected FLC reduction percentages positively correlated with substitution volumes. Total plasma proteins increased during RRT in the HDF group. CONCLUSIONS: This preliminary quantitative study demonstrates the superiority of high-efficiency HDF over high-flux HD for serum FLC removal in multiple myeloma patients on RRT. No negative impact on total plasma proteins was noted.

Optimal therapeutic conditions for online hemodiafiltration.

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.