Monitoring of ionized magnesium in hemodialysis patients: A useful tool to allow a personalized prescription of dialysate composition.

BACKGROUND AND AIMS: The dialysate magnesium (Mg) concentration is a major determinant of Mg balance in hemodialysis. This study aimed to assess the systemic variations of total (tMg) and ionized Mg (iMg) during a dialysis session using acetate or citrate fluids and 0.5 or 0.75 mM Mg. MATERIALS AND METHODS: 134 patients in maintenance hemodialysis were assigned to a dialysis session with 4 different dialysates: acetate fluid with 0.5 mM Mg (1) or 0.75 mM Mg (2), citrate fluid with 0.5 mM Mg (3) or 0.75 mM Mg (4). Ionized form was measured by direct ion-selective electrode. RESULTS: A Mg loss was observed in both acetate (0.12 and 0.08 mmol/L) and citrate (0.13 and 0.14 mmol/L for tMg and iMg, respectively) fluid groups containing 0.5 mM Mg. The use of acetate and citrate dialysates with 0.75 mM Mg led to a significant median intra-dialytic increase of 0.15 and 0.08 mmol/L for tMg, respectively. A significant augmentation in iMg concentration with acetate (0.11 mmol/L) but not with citrate dialysate (0.02 mmol/L) was observed. CONCLUSION: While a dialysate Mg concentration at 0.5 mM leads to a negative balance, increasing the concentration to 0.75 mM significantly raises post-dialysis circulating Mg. Monitoring of iMg should allow a personalized prescription in dialysate Mg.

Does the interference phenomenon affect strength development during same-session combined rehabilitation program in hemodialysis patients?

INTRODUCTION: This study aimed to assess if an interference effect could blunt the neuromuscular gains induced by a same-session combined rehabilitation in hemodialysis (HD) patients. METHODS: Patients exercised twice a week, for 16 weeks, over their HD sessions. They were either always trained with resistance and endurance exercises (continuous training, "CONT") or alternatively with 1 week of resistance alternated with 1 week of endurance (discontinuous training, "DISC"). Adherence and workload were continuously recorded. Short Physical Performance Battery (SPPB) score, one-leg balance test, and handgrip and quadriceps strength were evaluated before and after training intervention. RESULTS: Adherence to both programs was high (>90%). SPPB score had significantly improved (CONT: +1.5 point, DISC: +1.2 pt, p < 0.001), like one-leg balance test (CONT: +3.7 s, DISC: +5.5 s, p < 0.05), handgrip strength of exercised (CONT: +5.5 kg, DISC: +5.6 kg, p < 0.001) and of nonexercised arm (CONT: +4.4 kg, DISC: +2.8 kg, p < 0.01) as well as maximal quadriceps strength (+22 N·m for dominant and +29 N·m for nondominant leg in both groups, p < 0.001) bearing no difference between the trainings. CONCLUSION: Same-session combined training does not induce an interference effect in HD patients and temporal separation of exercises does not optimize strength gains. These practical data may be relevant for clinicians and practitioners to alternate endurance and resistance exercises.

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.

Dynapaenia and sarcopaenia in chronic haemodialysis patients: do muscle weakness and atrophy similarly influence poor outcome?

BACKGROUND: Sarcopaenia, defined as a decline in both muscle mass and function, has been recognized as a major determinant of poor outcome in haemodialysis (HD) patients. It is generally assumed that sarcopaenia is driven by muscle atrophy related to protein-energy wasting. However, dynapaenia, defined as weakness without atrophy, has been characterized by a different disease phenotype from sarcopaenia. The aim of this study was to compare the characteristics and prognosis of sarcopaenic and dynapaenic patients among a prospective cohort of chronic HD (CHD) patients. METHODS: Two hundred and thirty-two CHD patients were enrolled from January to July 2016 and then followed prospectively until December 2018. At inclusion, weakness and atrophy were, respectively, evaluated by maximal voluntary force (MVF) and creatinine index (CI). Sarcopaenia was defined as the association of weakness and atrophy (MVF and CI below the median) while dynapaenia was defined as weakness not related to atrophy (MVF below the median, and CI above the median). RESULTS: From a total of 187 prevalent CHD patients [65% of men, age 65.3 (49.7-82.0) years], 44 died during the follow-up period of 23.7 (12.4-34.9) months. Sarcopaenia and dynapaenia were observed in 33.7 and 16% of the patients, respectively. Compared with patients with sarcopaenia, patients with dynapaenia were younger and with a lower Charlson score. In contrast, mortality rate was similar in both groups (38 and 27%, respectively). After adjustment for age, sex, lean tissue index, serum albumin, high-sensitivity C-reactive protein (hs-CRP), haemoglobin (Hb), normalized protein catabolic rate (nPCR), dialysis vintage and Charlson score, only patients with dynapaenia were at increased risk of death [hazard ratio (HR) = 2.99, confidence interval 1.18-7.61; P = 0.02]. CONCLUSIONS: Screening for muscle functionality is highly warranted to identify patients with muscle functional impairment without muscle atrophy. In contrast to sarcopaenia, dynapaenia should appear as a phenotype induced by uraemic milieu, characterized by young patients with low Charlson score and poor prognosis outcome independently of serum albumin, hs-CRP, Hb, nPCR and dialysis vintage.

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.

Randomised trial on clinical performances and biocompatibility of four high-flux hemodialyzers in two mode treatments: hemodialysis vs post dilution hemodiafiltration.

This prospective multicenter randomized comparative cross-over trial aimed at evaluating the influence of hemodialysis vs post-dilution hemodiafiltration with high-flux dialyzers in solute clearance and biocompatibility profile. 32 patients were sequentially dialyzed with Leoceed-21HX, Polypure-22S+, Rexsys-27H and VIE-21A. Primary outcome was ß2-microglobulin removal. Secondary outcomes were (i) extraction of other uremic solutes (ii) parameters of inflammation and nutrition and (iii) comparative quantification of perdialytic albumin losses (using total 'TDC' vs partial 'PDC' collection of dialysate). Significant increases in removal rates of ß2-microglobulin (84.7 ± 0.8 vs 71.6 ± 0.8 mg/L), myoglobin (65.9 ± 1.3 vs 38.6 ± 1.3 µg/L), free immunoglobulin light chains Kappa (74.9 ± 0.8 vs 55.6 ± 0.8 mg/L), ß-trace protein (54.8 ± 1.3 vs 26.8 ± 1.4 mg/L) and orosomucoid (11.0 ± 1.1 vs 6.0 ± 1.1 g/L) but not myostatin (14.8 ± 1.5 vs 13.0 ± 1.5 ng/mL) were observed in HDF compared to HD when pooling all dialyzers. Rexsys and VIE-A use in both HD and HDF subgroups was associated to a better removal of middle/large-size molecules compared to Leoceed and Polypure, except ß2-microglobulin for Rexsys. Inflammatory parameters were unchanged between dialyzers without any interaction with dialysis modality. Mean dialysate albumin loss was comparable between TDC and PDC (1.855 vs 1.826 g/session for TDC and PDC respectively). In addition, a significant difference in albumin loss was observed between dialyzers with the highest value (4.5 g/session) observed using Rexsys. Use of all dialyzers was associated with good removals of the large spectrum of uremic toxins tested and good biocompatibility profiles, with an additional gain in removal performances with HDF. Larger surface area, thinner wall and resultant very high ultrafiltration coefficient of Rexsys should be taken into account in its clear performance advantages.

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.

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.

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.

Bisphenol A in chronic kidney disease.

The estrogenic endocrine-disrupting substance bisphenol A (BPA) is extensively used as a starting material for a variety of consumer plastic products including dialyzer materials. The present study was performed to explore plasma BPA levels in patients with impaired renal function and to investigate if dialyzers differing in elutable BPA influence plasma levels in patients on maintenance hemodialysis. In vitro BPA was eluted from high-flux polyethersulfone (PUREMA H, referred as PUR-H), high-flux polysulfone (referred as HF-PSu), and low-flux polysulfone (referred as LF-PSu) dialyzers by recirculation with water for 180 min. In a cross-sectional clinical study, plasma BPA levels of outpatients with different stages of chronic kidney disease (CKD) from four different centers were determined. Furthermore, in a prospective, randomized, and crossover setting, 18 maintenance dialysis patients were subjected successively to 4 weeks of thrice-weekly hemodialysis with each LF-PSu, HF-PSu, and PUR-H. In addition, the fractions of protein-bound and free BPA were determined in a subset of dialysis patients. The mass of BPA eluted from the blood compartments in vitro under aqueous conditions varied for the three dialyzers being very low for PUR-H (6.2 ± 2.5 ng; P < 0.001), intermediate for HF-PSu (48.1 ± 7.7 ng), and highest for LF-PSu (140.8 ± 38.7 ng; P < 0.01). In 152 prevalent patients with CKD enrolled in the cross-sectional trial, plasma BPA started to rise after stage 3. Maintenance hemodialysis patients had more than six times higher BPA concentrations than patients with CKD stage 5 not yet on dialysis (10.0 ± 6.6 vs. 1.6 ± 1.8 ng/mL; P < 0.001). The BPA concentrations highly and inversely correlated with renal function. In the randomized controlled study, the plasma BPA concentrations were highly elevated compared with healthy controls (range 9.1 ± 4.5-12.0 ± 6.0 ng/mL vs. ≤0.2 ± 0.1 ng/mL; P < 0.001), but no change of the plasma levels was observed during hemodialysis with any of the three dialyzers in the course of a single treatment and over a period of 4 weeks. The protein-bound fraction of plasma BPA in the dialysis patients was 74 ± 5%. Renal function and, most likely, the total quantity of ingested BPA are essential parameters affecting plasma BPA concentrations. Dialyzers are one additional source of BPA, but differences in the elutable BPA content are not associated with a significant effect on BPA plasma levels in Western European maintenance dialysis patients. Due to high protein binding, the removal of BPA by hemodialysis is limited.

Does hemodiafiltration improve the removal of homocysteine?

High prevalence of hyperhomocysteinemia is common in hemodialysis (HD) patients and could contribute to worsen the cardiovascular risk. Beyond vitamin B status, dialysis modality itself could influence homocysteine (Hcy) levels. The objective was compare the reduction rate (RR) of Hcy and cysteine in stable dialyzed patients treated by standard HD or hemodiafiltration (HDF). Seventy-five patients undergoing stable dialysis through standard high-flux HD (n = 35) or HDF (n = 40) were included. Biological parameters were determined before and after a midweek dialysis session. Urea percent reduction per session and Kt/V index (K, body urea clearance, T, time of dialysis, and V, urea distribution volume), defined as a marker of dialysis efficacy, were similar between HD and HDF groups. By contrast, higher RR of beta2 microglobulin (ß2m) was observed in HDF compared with HD (78.6 vs. 72.0%, respectively; P < 0.001). Likewise, higher RR of Hcy was obtained with HDF compared to HD (46.0 vs. 41.5%, respectively; P < 0.05), whereas the RR of cysteine was similar in both groups. Interestingly, a positive correlation between Hcy RR and urea Kt/V index was observed (r = 0.29, P < 0.05) and between Hcy RR and ß2m RR (r = 0.45, P < 0.001). Time-averaged concentration (TAC) of Hcy was lower with HDF compared with HD (17.8 vs. 19.1 µmol/L, respectively), although not significant. There was no difference in median Hcy according to dialysis modality for neither pre- nor postdialysis levels. Significant higher removal of Hcy was observed with HDF compared with standard HD, although urea Kt/V index was similar. Enhanced removal of middle molecules, such as ß2m, could be involved in Hcy RR improvement with HDF.

Whole-blood viscosity increases significantly in small arteries and capillaries in hemodiafiltration. Does acute hemorheological change trigger cardiovascular risk events in hemodialysis patient?

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.

Protein-bound uraemic toxin removal in haemodialysis and post-dilution haemodiafiltration.

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.

[How to estimate the dietary protein intake of a hemodialysis patient? What formulate to use in practice?]. / Comment évaluer l'apport protidique d'un patient hémodialysé ? Quelles formules utiliser en pratique ?

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.