Short-Term Effects of Branched-Chain Amino Acids-Enriched Dialysis Fluid on Branched-Chain Amino Acids Plasma Level and Mass Balance: A Randomized Cross-Over Study.

OBJECTIVE(S): The hemodialysis (HD) session per se is a catabolic event contributing to protein-energy wasting via several mechanisms including nutrient losses. Amino acids (AAs) losses in the dialysate are estimated from 6 to 10 g per treatment. The HD patient plasma AA concentration is usually lower than in normal subjects. This is even more marked in patients with long dialysis vintage or malnutrition. METHODS: The aim of the study was to evaluate the effect on mass balance of a branched-chain AA (BCAA)-enriched (valine, isoleucine, leucine) dialysis fluid in a group of 6 stable HD anuric patients, fasting since 12 hours. The specific choice of BCAA relied on their key role on protein and muscle anabolism and their usual decreased plasma concentration in HD patients. Each patient was prescribed in a cross-over design and random order, either receiving a standard high-flux HD or an HD treatment using a BCAA-enriched acid concentrate designed to achieve a physiological plasma concentration of BCAAs. HD prescription remained unchanged during the 2 phases of study. Dialysate electrolytes prescription was kept constant for each individual patient, as well as dialysate glucose concentration (5.5 mmol/L). Pre- and post-dialysis BCAAs concentrations were measured by Ion-Exchange Liquid Chromatography. Postdialysis concentrations were corrected for hemoconcentration, and net mass transfer was calculated. RESULTS: Six stable prevalent end-stage kidney disease patients were studied. They consisted of 5 men and 1 woman, aged 69.9 years, with body mass index of 25.2 kg/m2. Treatment schedule consisted of treatment time 4 hours, high-flux polysulfone membrane (1.8 m2), blood flow 350 mL/minute, and dialysate/blood flow ratio at 1.5. The average BCAAs concentration in dialysate was targeted to physiological levels and assessed in 6 different samples, respectively for plasma valine, isoleucine, and leucine at 271, 78, and 145 µmol/L. With standard dialysate, plasma valine decreased from 204.5 to 130.8 (P = .0014). Plasma isoleucine and leucine changes were not significant, respectively from 65.7 to 59.3 µmol/L and 110.3 to 113.4 µmol/L. When using the BCAA-enriched dialysis fluid, plasma valine increased from 197.2 to 269.2 µmol/L (P = .0001), plasma isoleucine and leucine respectively from 63.2 to 84.7 (P = .0022) and from 107.2 to 161.6 µmoles/L (P = .0002). Dialysis dose estimated from KT/V did not differ between the sessions. The mass transfer with BCAA-enriched dialysate was +115, +16, and + 83 µmol per session for leucine, isoleucine, and valine, respectively. CONCLUSION(S): In conclusion, the addition of BCAAs at physiological concentration in the dialysis fluid contributes to restore physiological plasma concentrations for valine, isoleucine, and leucine at the end of a dialysis session. As BCAAs are essential to muscle balance, this could help to limit losses of BCAAs, restore physiological BCAAs concentrations, and decrease muscle catabolism observed during the HD treatment. Further outcome-based studies are needed to confirm this hypothesis on a larger scale and longer treatment time.

Even a Moderate Fluid Removal Rate during Individualised Haemodialysis Session Times Is Associated with Decreased Patient Survival.

BACKGROUND: Several studies report that fluid removal rate (FRR) above 10-13 mL/h/kg is associated with increased mortality in haemodialysis (HD) patients. AIM: The aims of this study are to assess the influence of moderate FRR on survival in a cohort of prevalent dialysis patients with various dialysis session times and to challenge the FRR thresholds associated with increased mortality risk reported previously. METHODS: Interdialytic weight gain (IDWG) and FRR (calculated from ultrafiltration [UF], target weight, and session time prescriptions) were studied in 190 prevalent dialysis patients (female: 42%, mean age: 69.5 years, median vintage: 40.2 months, diabetes: 34.7%, loop diuretic prescription: 5.8%) and averaged during the final quarter of 2010. Patient survival was analysed using Kaplan-Meier and Cox-multivariate analyses. RESULTS: The median IDWG, median session time, and median FRR were 2.33 kg (-0.54-4.57), 5.0 h (3.9-8.0 h), 6.8 mL/h/kg (1.3-16.7), respectively, and FRR was ≥10 mL/h/kg in 11.6% of the patients. The Kaplan-Meier analysis showed decreased patient survival when the FRR was above the median (6.8 mL/h/kg; p = 0.012). The FRR was found to be independently associated with increased mortality (hazard ratio 1.15 [95% CI 1.02-1.29]; p = 0.027) using stepwise Cox proportional hazard regression analysis, including age, vintage, gender, body mass index (BMI), serum albumin level, ß2-microglobulin level, cardiovascular and diabetes history, and session time. Online haemodiafiltration did not change this result. The role of residual renal function was unlikely because 74% of the patients had a vintage of >18 months, a minority (5.8%) were prescribed loop diuretics (a surrogate of significant urine output) and ß2-microglobulin level was not different in patients who were below or above the FRR median. CONCLUSION: We concluded that the FRR threshold above which there is an increased mortality is lower than what has been reported (7.8 mL/h/kg). It raises the question of the hazard of fluid removal and intermittence of standard HD.

Analysis of the kinetics of the parathyroid hormone, and of associated patient outcomes, in a cohort of haemodialysis patients.

BACKGROUND: Observational studies have recently associated a decrease in serum parathyroid hormone (PTH) level with a higher rate of mortality among hemodialysis (HD) patients. Decreases in PTH level can result from medical intervention (MPD) and surgical parathyroidectomy (PTX), or may occur spontaneously, usually associated with an underlying malnutrition-inflammation syndrome (SPD). The aim of our study was to prospectively identify the incidence of decreases in PTH level in a cohort of HD patients and the frequency distribution of the different causes (MPD, PTX and SPD), as well as to evaluate the survival outcomes for each PTH group (MPD, PTX and SPD) compared to patients who did not experience a PTH decrease over the first 36 months of the study (NPD). METHODS: The 197 patients receiving HD at our center in January 2010, and meeting our eligibility criteria, were enrolled in our prospective study, and were observed for a period of 60 months. A decrease in PTH level >50 % between two successive PTH measurements obtained within an interval <3 months was defined as a significant event. MPD referred to a decrease in PTH due to an increased oral calcium intake, increased dialysate calcium concentration (DCC), increased alfacalcidol use, or use of cinacalcet therapy. A surgical 7/8 PTX was performed in young patients or in patients in whom cinacalcet therapy failed. SPD referred to a decrease in PTH related to a medical or surgical event. Baseline characteristics among patients in each group (MPD, PTX, SPD, and NPD) were evaluated using Fisher's exact test. The 60-month survival was evaluated using Kaplan-Meier and Cox multivariable proportional hazards models. Univariate and multivariate Cox analyzes were used identify variables with mortality. The relative risk of mortality was expressed as a hazard ratio (HR). RESULTS: The distribution of the 197 patients forming our four study groups was 34 % in the NPD group, 35 % in the SPD group, 25 % in the MSD group and 6 % in the PTX group. Among patients in the SPD group, the main acute comorbid conditions were peripheral vascular and cardiac complications, sepsis, fractures, and cancers with an increase in serum CRP level (from 14.3 ± 18 to 132 ± 90 mg/L) and a decrease in serum albumin (from 33 ± 4.5 to 28.6 ± 4 g/L). In the MPD group, the main therapeutic change was an increase in DCC, either independently or in association with cinacalcet therapy. The median survival rate among patients was 10 months for SPD, compared to 22 months among patients in the MPD group (p < 0.001). Using multivariable Cox model and taking the NPD group as reference, the risk of mortality was lower among patients in the MPD group (HR, 0.42[0.2-0.87] p = 0.01), with survival being comparable for the SPD and NPD groups (HR, 1.3 [0.75-2.2]). No mortality was observed in the PTX group. CONCLUSION: The poor outcomes associated with SPD, related to acute comorbid conditions, should not lead to undertreat secondary hyperparathyroidism whose appropriate medical or surgical therapies are associated with better outcomes.

Online-haemodiafiltration vs. conventional haemodialysis: a cross-over study.

BACKGROUND: The main short-term advantages of haemodiafiltration (HDF) are supposedly better removal of Beta2-microglobulin (ß2-m) and phosphate, and better haemodynamic stability. The main disadvantage is higher costs. The aim of the study was to compare the clinical and biological parameters associated with HDF and high-flux haemodialysis (HD), using a cross-over design, while maintaining the same dialysis parameters. METHODS: All patients on a 3 × 4 hours schedule were observed during 3 identical 6-months periods: HDF1 - HD - HDF2. The mean values for the 2 last months of each period were compared. RESULTS: A total of 51 patients (76 % males, 45 % diabetic) with a mean age of 74 ± 15 years, and who had been on dialysis for 49 ± 60 months were included. The mean blood flow (329 ± 27 ml/min), dialysate flow (500 ml/min), and convection volumes (21.6 ± 3.2 L) were recorded. Patient medications were not changed. Predialysis blood pressure, phosphataemia, calcaemia, iPTH, Kt/V, nPNA and intradialytic events were similar throughout the 3 periods. Only serum albumin (34. 4 ± 3.6, 35.9 ± 3.4, 34.1 ± 4 g/L, p < 0. 0001) and ß2-m serum levels (26.1 ± 5.4, 28 ± 6, 26.5 ± 5 mg/L, p < 0.001, values shown for HDF1, HD, HDF2, respectively) were significantly lower during the HDF periods. Factor associated with higher delta serum albumin levels between HD and HDF periods was mainly a lower convection volume. CONCLUSION: Comparing HDF and HD, we did not observe any differences in haemodynamic stability or in serum phosphate levels. Only serum ß2-m (-6% vs. HD) and albumin (-5% vs. HD) levels changed. The long-term clinical consequences of these biochemical differences should be prospectively assessed.

Target weight gain during the first year of hemodialysis therapy is associated with patient survival.

BACKGROUND: Hemodialysis (HD) patients are exposed to a high risk of death. Nutritional status has been recognized as a key factor for patient survival. Nutritional markers have been shown to improve after HD onset. In this study we have analyzed the dynamics of target weight (TGW) change and the evolution of other nutritional parameters during the first year of HD treatment and their influence on patients' outcomes. METHODS: We have analyzed a retrospective cohort of incident patients starting HD therapy between January 2000 and January 2009, and studied the values and changes in TGW, interdialytic weight gain (IDWG), predialysis systolic blood pressure, serum albumin, protein intake, C-reactive protein (CRP) from the start and first week (W1), W8, W12, W26 and W52 in patients who survived the first year of therapy. We have analyzed the relationship between TGW changes with other nutritional parameters and the patient survival. RESULTS: Among the cohort including 363 patients starting HD therapy, 251 (age 65.8 ± 14.8 years, 93 female/158 male, diabetes 36%) survived at least 1 year after dialysis onset and were followed for 44.9 months. During the first 8 weeks, the TGW decreased by 6.5 ± 5.6% (initial TGW change). The initial TGW change was correlated with IDWG at W12 and W26, and with changes in serum albumin and nPNA (normalized protein equivalent of nitrogen appearance) between HD W1 and W52 (respectively +7.8 and +11.4%). From W8 to W52, the TGW increased by +1.9 ± 7.4% (secondary TGW change). The Kaplan-Meier analysis displayed a significantly better survival in patients above the median (+2.3%) of the secondary TGW change (respectively -3.6 ± 5.2% and +7.6 ± 4.5%). The two groups above and below this median were not different according to age, diabetes or cardiovascular event history but the patients above the median had a significant higher IDWG and protein intake. In the Cox model analysis the patient overall mortality was related to age (p < 0.0001), to the secondary TGW change (p = 0.0001), and to the CRP level at W52 (p < 0.0001). CONCLUSIONS: The initial fluid removal was related to nutritional markers. The secondary TGW change during the first year of HD treatment calculated after the initial phase of fluid removal was identified as a strong predictor of survival. It was associated with a better food intake whereas the patient case mix was not different. These data highlight the importance of nutrition and food intake in the first year of dialysis therapy and the need for nutritional follow-up and support in incident HD patients. It stresses the need in understanding the key factors associated with food intake in this setting.

Biological impact of targeted dialysate calcium changes in haemodialysis patients: the key role of parathyroid hormone.

BACKGROUND: Establishing an optimal dialysate calcium (DCa) concentration in haemodialysis patients is crucial. DCa individualization has been advocated but most dialysis centres use a fixed DCa, preferably 1.25 mmol/L in the USA and 1.5 mmol/L in European countries. The aim of the study was to assess the short-term biological impact of individual DCa prescription aiming at maintaining normal serum calcium and serum parathyroid hormone (PTH) between 150 and 300 pg/mL. METHODS: Between January 2008 and December 2010, all prevalent patients were checked for the need for DCa change according to our usual strategy. Baseline (T0) and after 3 months (T3), values were compared for serum calcium, phosphate, total alkaline phosphatases (t-ALP) and PTH. RESULTS: Seventy-eight patients were followed up for analysis with only one DCa change. Vitamin D derivatives, oral calcium and cinacalcet doses remained stable. Increasing DCa from 1.25 to 1.5 mmol/L and from 1.5 to 1.75 mmol/L led to a significant increase of calcaemia (+2.2 and +1.7%) and a decrease of phosphataemia (-7 and -9%), t-ALP (-10 and -12%) and PTH (-50 and -62%). Decreasing DCa from 1.75 to 1.5 mmol/L and from 1.5 to 1.25 mmol/L led to a decrease of calcaemia (-2.5 and -1.7%) and an increase of phosphataemia (+11 and +12%), t-ALP (+12 and +10%) and PTH (+138 and +175%). CONCLUSIONS: DCa individualization has a significant impact on mineral metabolism parameters, especially on serum PTH levels, and could be considered as an additional therapy in a more global strategy together with phosphate binder, vitamin D and calcimimetics prescription.

Physical activity and energy expenditure in haemodialysis patients: an international survey.

BACKGROUND: The assessment of physical activity and energy expenditure is relevant to the care of maintenance haemodialysis (MHD) patients. In the current study, we aimed to evaluate measurements of physical activity and energy expenditure in MHD patients from different centres and countries and explored the predictors of physical activity in these patients. METHODS: In this cross-sectional multicentre study, 134 MHD patients from four countries (France, Switzerland, Sweden and Brazil) were included. The physical activity was evaluated for 5.0 ± 1.4 days (mean ± SD) by a multisensory device (SenseWear Armband) and comprised the assessment of number of steps per day, activity-related energy expenditure (activity-related EE) and physical activity level (PAL). RESULTS: The number of steps per day, activity-related EE and PAL from the MHD patients were compatible with a sedentary lifestyle. In addition, all parameters were significantly lower in dialysis days when compared to non-dialysis days (P < 0.001). The multivariate regression analysis revealed that diabetes and higher body mass index (BMI) predicted a lower PAL and older age and diabetes predicted a reduced number of steps. CONCLUSIONS: The physical activity parameters of MHD patients were compatible with a sedentary lifestyle. This inactivity was worsened by aging, diabetes and higher BMI. Our results indicate that MHD patients should be encouraged by the health care team to increase their physical activity.

Predialysis systolic blood pressure evolution in incident hemodialysis patients: effects of the dry weight method and prognostic value.

BACKGROUND: The relationship between predialysis blood pressure (BP) and hemodialysis (HD) patient outcomes is controversial. We report the evolution of predialysis BP in incident patients treated with the dry weight method and its relationship with patients' outcomes. METHODS: Between January 2000 and 2009, 308 patients started HD treatment. Fluid was progressively removed. The patients were encouraged to accept long-hour dialysis session and to follow a salt-restricted diet. BP and body weight (BW) were recorded and analyzed at start (week 1, W1) and weeks 8, 12, 26 and 52. RESULTS: The predialysis systolic BP decreased from 142.1 at W1 to 130.7 mm Hg at W52. Postdialysis BW decreased from W1 to W8 (-5.0 ± 4.5%). It was correlated with the decrease of the predialysis systolic BP at W26 and W52. Whereas the patient survival was significantly lower in the lower predialysis systolic BP tertile at W1 like in previous reports calling this phenomenon 'reverse epidemiology', no relationship between predialysis BP levels and outcomes was found at W12, W26 and W52. The patients in the tertile of the greater predialysis systolic BP decrease at W12 had significantly better survival in the whole group and in hypertensive patients. This relationship remained significant in the Cox proportional-hazards analysis. CONCLUSIONS: Hence the dry weight method is efficient in decreasing the predialysis BP in incident HD patients. The initial BW decrease was correlated with BP decrease at W26 and W52. Early correction of BP by fluid removal erases the reverse epidemiology for BP and influences positively the patient survival.

[Natriuretic peptides in dialysis: From theory to clinical practice]. / Les peptides natriurétiques en dialyse : de la théorie à la pratique.

Cardiologists and emergency-wards physicians are used to check natriuretic peptides serum level, mainly B-type natriuretic peptide and N-terminal pro-Brain natriuretic peptide for acute cardiac failure diagnosis. Due to their accumulation in chronic kidney disease and their elimination by dialysis, natriuretic peptides sampling remains debatable in chronic kidney disease patients. In dialysis patients, high natriuretic peptides values are associated with mortality, left ventricular hypertrophy and cardiac failure. However, a single value cannot provide a reliable diagnosis. Our clinical practice is as follows: First, we prefer B-type natriuretic peptide to N-terminal pro-Brain natriuretic peptide because of its shorter half-life, with less impact of renal function and dialysis, making its interpretation easier in case of advanced chronic kidney disease or in dialysis patients; second, we define a reference value of B-type natriuretic peptide at dry weight from serial measurements; third, the B-type natriuretic peptide changes are interpreted according to extracellular fluid and cardiac status, but also from the arteriovenous fistula blood flow. In stable dialysis patients, B-type natriuretic peptide is sampled monthly and weekly in unstable patients. We illustrate our experience using clinical cases of overhydration, new cardiac disease onset, hypovolemia and arteriovenous fistula with high blood flow. Longitudinal follow-up of B-type natriuretic peptide is an important advance in dialysis patients in order to detect and treat extracellular fluid variations and cardiac disease status early, both important factors associated with hard outcomes.

The effect of protein-enriched snacks on serum albumin concentration in non-selected haemodialysis patients.

OBJECTIVE: Serum albumin level is not only one of the protein-energy wasting criteria but also a powerful marker of mortality in patients on haemodialysis (HD) treatment. The study aimed to assess the effect of a protein-enriched snack given during HD treatment on serum albumin level. DESIGN AND METHODS: This prospective, single-centre, observational, non-randomized 16-month study was sub-divided into four 4-month periods. Patients on hemodialysis for more than three months and receiving a regular standard snack (8.8 g of protein) during the HD session were included and assigned during four four-month periods to receive either the standard snack or a protein-enriched snack (28.7 g). Patients were not selected based on nutritional criteria. RESULTS: Sixty-six patients completed the study. Serum albumin levels significantly increased, from 3.43 ± 0.28 g/dl in the first period (standard snack) to 3.62 ± 0.32 g/dl (p < 0.0001) in the second period (enriched snack). In the third period (standard snack), albumin levels remained stable (3.61 ± 0.35 g/dl). After the fourth period (enriched snack), serum albumin levels further increased significantly (3.69 ± 0.30 g/dl; p = 0.05 and p = 0.007, respectively). Weight and normalized protein nitrogen appearance remained stable during the 16-month study period. CONCLUSIONS: This study suggests that the intake of a protein-enriched snack during HD treatment, independently from baseline serum albumin level, could significantly increase their serum albumin levels. Serum albumin level is a powerful predictor of mortality; therefore, this simple and effective action could be of real interest to improve patients' outcomes.

[Comparison of citrate 4% and heparin as tunneled-catheters-locking solution in chronic hemodialysis]. / Comparaison des verrous de cathéters tunnellisés par citrate 4 % et héparine en hémodialyse chronique.

INTRODUCTION: Citrate 4% is an alternative to heparin as catheter-locking solution in chronic hemodialysis patients. We compared catheter dysfunction episodes, dialysis adequacy, plasminogen-tissular activators use and costs according to catheter-locking solution in our centre. METHODS: Prospective, monocentric, cohort study (NephroCare Tassin-Charcot) on 49 prevalent patients in chronic hemodialysis. Two main groups were formed according to the prescription of catheter-locking solution at the beginning of the study (03/02/2016) and followed until 05/10/2016: heparin (n=26) and citrate (n=22). RESULTS: The number of diabetic patients was higher in the citrate group (12/22) than in the heparin one (5/26; P=0.025). The 2 groups were comparable for the other studied variables. We didn't observe any difference in terms of catheter-dysfunction (4.23 versus 4.14% in heparin and citrate groups, respectively; P=1.0) and dialysis adequacy. The prescription of citrate was associated with lower TPA uses (1/604 versus 14/946; P=0.022) and lower costs (1.42 € for one session versus 2.94 €). CONCLUSION: Administration of citrate 4% as a catheter-locking solution is not inferior to heparin in terms of catheter-dysfunction episodes, is associated with similar dialysis adequacy results, lower plasminogen-tissular activators uses and reduced costs in chronic prevalent hemodialysed patients.

Severe secondary hyperparathyroidism in patients on haemodialysis is associated with a high initial serum parathyroid hormone and beta-CrossLaps level: Results from an incident cohort.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is a frequent complication of renal disease and most commonly occurs in patients on haemodialysis (HD) with metabolic, vascular, endocrine, and bone complications. The aim of this study was to analyze the evolution of mineral metabolism parameters during the first 36 months of HD treatment and identify the initial factors associated with severe SHPT. METHODS: Serum parathyroid hormone (PTH), calcium and phosphate levels were measured monthly; bone-specific alkaline phosphatase (b-ALP) and beta-CrossLaps (CTX) were measured biannually. Severe SHPT was defined as the need for cinacalcet treatment. Patients with less than 24 months of follow-up were excluded. RESULTS: One hundred thirty-three incident HD patients were included. Baseline mean PTH was 275 ± 210 pg/mL. After an initial drop at the third month (172 ± 133 pg/mL), the serum PTH level progressively increased to the maximum at 36 months (367 ± 254 pg/mL). This initial drop was associated with the initial correction of both hypocalcaemia and hyperphosphataemia. Serum CTX and b-ALP revealed no significant changes over time. Severe SHPT was observed in 18% of patients and was associated with higher mean calcaemia and phosphataemia. In logistic regression, the initial factors associated with the risk of severe SHPT were: female sex, higher baseline PTH and CTX values. A receiver operation characteristic curve analysis identified a cut-off value of >374 pg/mL for baseline PTH and >1.2 µg/L for CTX for increased risk of developing severe SHPT. The relative risk of developing severe SHPT was 3.7 (1.8-7.5, p = 0.002) for high baseline CTX, 4.9 (2.4-9.7, p = 0.001) for high baseline PTH, and 7.7 (3.6-16, p< 0.0001) when both criteria were present. CONCLUSION: After an initial drop, a progressive increase in the serum PTH level during the first 3 years of HD treatment was observed despite aggressive therapy. High baseline levels of PTH and CTX increased the risk of developing severe SHPT.

Brain Natriuretic Peptide Is a Marker of Fluid Overload in Incident Hemodialysis Patients.

BACKGROUND/AIMS: Brain natriuretic peptide (BNP) is secreted by cardiomyocytes under stretch condition. High blood levels are associated with decreased patient survival in heart failure patients and in hemodialysis (HD) patients. We report the monthly BNP change in the first months of HD therapy in incident patients and its relationship with fluid removal and cardiac history (CH). METHODS: All patients starting HD therapy in our unit from May 2008 to December 2012 were retrospectively analyzed. Every month (M1 to M6), BNP was assessed before a midweek dialysis session. CH, monthly pre- and postdialysis blood pressure, and postdialysis body weight were collected. RESULTS: A total of 236 patients were included in the analysis. The median BNP at HD start was 593 (175-1,433) pg/mL, with a significant difference between CH- and CH+ patients (291 vs. 731 pg/mL, p < 0.0001). Mortality was significantly higher in patients in the higher BNP tertile. BNP decreased significantly between M1 and M2 and then plateaued. The BNP change between M1 and M2 and between M1 and M6 was significantly correlated with the initial fluid removal. Applying stepwise multiple regression, the BNP change between M1 and M2 was significantly and independently related to fluid removal. The BNP level at M6 was also related to patient survival. CONCLUSIONS: We confirm that in incident HD patients, BNP level is related to fluid excess and cardiac status. The BNP decrease in the first months of HD therapy is related to fluid excess correction. BNP appears as an important tool to evaluate hydration status correction after HD onset.

Vascular Calcification Progression Is an Independent Predictor of Mortality in Patients on Haemodialysis.

BACKGROUND: We previously reported that vascular calcification (VC) score was associated with mortality in patients on haemodialysis (HD) and that a high serum level of parathyroid hormone (PTH) and fibroblast growth factor (FGF)-23 were the only factors associated with VC progression. AIM: To assess the impact of VC progression on HD patient survival. METHODS: The study cohort including 85 HD patients studied between 2006 and 2007 and between 2009 and 2010 was divided into patients with VC progression (PG+, n = 38) and no-progression (PG-, n = 47), based on VC scores measured twice at 3-year intervals (VC1 and VC2). Patients were followed during 3 additional years. RESULTS: Kaplan-Meier analysis determined that PG+ displayed increased mortality (hazard ratio (HR): 2.4; 95% confidence interval (CI): 1.12-4.8; p = 0.03). This result was confirmed using a Cox proportional hazards model adjusted for age, dialysis duration, the VC1 score, and the mean FGF-23 and iPTH serum levels (HR: 2.7; 95% CI: 1.12-6.6; p = 0.02). CONCLUSION: VC progression is associated with poor survival in patients on HD, irrespective of a patient's baseline VC score.

Usefulness and feasibility of measuring ionized calcium in haemodialysis patients.

BACKGROUND: Measuring blood calcium level is recommended in haemodialysis (HD) patients. The Kidney Disease Improving Global Outcomes position states that the measurement of ionized calcium (ICa) level is preferred, but in the clinical setting, due to technical difficulties, total calcium (tCa) level is preferred to ICa. AIM: The aim of this study was to test the possibility of delayed ICa analysis using frozen serum, and so to identify the factors associated with predialysis ICa level and compare the ability of tCa and Alb-Ca to predict ICa level and finally to compare the survival rate according to the three calcium measurements. METHODS: All prevalent HD patients, dialysed by a native AV fistula in a 3 × 4 to 3 × 8 h schedule, had their predialysis ICa, tCa and Alb-Ca levels and usual mid-week biology recorded. Intergroup comparisons between ICa quartile were performed. Bland-Altman plots and linear regression were used to assess the differences between 30 fresh and frozen samples. Survival analyses were performed using ICa and tCa levels. RESULTS: Comparing fresh blood and frozen serum samples, linear regression (y = 0.98 + 0.02, r = 0.961) showed that the two methods were quite identical with the same mean ICa value (1.1 ± 0.1 mmol/L, P = 0.45). A total of 160 HD patients were included in the study. Hypocalcaemia, using ICa values, was highly prevalent in our population (40%) whereas hypercalcaemia was observed only in three cases (1.8%). In predicting ICa hypocalcaemia (<1.12 mmol/L, n = 64), the use of tCa was accurate in 48.4% of patients, and the use of Alb-Ca was accurate in only 17.2% of patients; tCa was not a predictive factor for hypercalcaemia (ICa > 1.32 mmol/L, n = 3); Alb-Ca value predicted hypercalcaemia in 2/3 of the patients. In predicting normocalcaemia, the use of tCa values was correct in 92.4% of patients and the use of Alb-Ca values in 88.1% of patients; only younger age (P = 0.03) and female sex (P = 0.01) were associated with higher ICa quartile. None of the three calcium measures was significantly associated with survival rate using log-rank and Cox models adjusted for age, dialysis vintage, diabetes and sex. CONCLUSION: In the present study, we report that (1) delayed ICa measure is feasible in dialysis patients using a freezing technique, (2) hypocalcaemia is highly prevalent in HD patients and poorly predicted by Alb-Ca level, (3) the main factor associated with ICa level is sex of the individual and (4) calcaemia is not associated with survival rate using any of the three methods.

[Bone biomarkers in haemodialysis patients: bone alkaline phosphatase or ß-Crosslaps?]. / Quels marqueurs osseux chez les patients hémodialysés: phosphatases alcalines osseuses ou ß-CrossLaps?

BACKGROUND: Bone turnover (BT) abnormalities are frequently observed in patients with chronic kidney disease. Bone biopsy remains the gold standard for diagnosis; however, its invasive nature has led to its decreased utilisation. The serum parathyroid hormone (PTH) level is not a reliable bone marker (BM) for BT assessment. The latest international recommendations suggest the use of total alkaline phosphatase (t-ALP) or bone-specific alkaline phosphatase (b-ALP), but not ß-CrossLaps (CTX). We compared b-ALP, t-ALP, and CTX levels in patients on haemodialysis (HD). METHODS: All HD patients at a single institution following a standard 3×4 to 3×5 hours schedule were included in the study, provided they were free from liver disease. Serum intact PTH, t-ALP, b-ALP, and CTX values were compared at baseline and after 18 months of treatment. A kinetic study was performed for pre- and postdialysis CTX values over a 2-week period. We described the longitudinal evolution of these BMs in two typical patients. RESULTS: A total of 98 patients on HD (46% female) were evaluated. The mean age was 69.8±11 years and the mean duration of dialysis was 54.4±61 months. At baseline, CTX (2.1±1 µg/L) correlated well with b-ALP (18±11 µg/L; r=0.64; P<0.001) and PTH (221±165 pg/mL; r=0.62; P<0.001). The changes in these values at 18 months were also correlated (ΔCTX compared with Δb-ALP: r=0.51; P<0.001; Δb-ALP compared with ΔPTH: r=0.37, P<0.01). b-ALP and t-ALP (245±132 U/L) were closely correlated (r=0.78), as was their variation over 18 months (r=0.67), but t-ALP did not correlate with PTH, and correlated poorly with CTX (r=0.38). The CTX reduction ratio during standard dialysis was approximately 70 to 75% over each session, although predialysis values remained stable. CONCLUSION: In HD patients, mean CTX values are five times higher than the normal range. CTX appears to be an alternative to b-ALP for assessing BT. b-ALP remains the standard BM, despite being expensive, infrequently available in many laboratories, and not useful for patients with liver disease.