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Rationale and Objective: This study aimed to develop a cosmesis scale to evaluate the cosmetic appearance of hemodialysis (HD) arteriovenous (AV) accesses from the perspective of the patient and clinician, which could be incorporated into clinical trials., Study Design: Using a modified Delphi process, two AV access cosmesis scale (AVACS) components were developed in a four-round Delphi panel consisting of two surveys and two consensus meetings with two rounds of patient consultation., Setting and Participants: The Delphi panel consisted of 15 voting members including five interventional or general nephrologists, five vascular surgeons, three interventional radiologists, and two vascular access nurse coordinators. Four patients experienced with vascular access were involved in patient question development., Analytical Approach: For a component to be included in the AVACS, it had to meet the prespecified panel consensus agreement of ⩾70%., Results: The clinician component of the AVACS includes nine questions on the following AV access features: scarring, skin discoloration, aneurysm/pseudoaneurysms and megafistula appearance. The patient component includes six questions about future vascular access decisions, interference with work or leisure activities, clothing choices, self-consciousness or attractiveness, emotional impact, and overall appearance., Limitations: Delphi panel methods are subjective by design, but with expert clinical opinion are used to develop classification systems and outcome measures. The developed scale requires further validation testing but is available for clinical trial use., Conclusions: While safety and efficacy are the primary concerns when evaluating AV access for HD, cosmesis is an important component of the ESKD patient experience. The AVACS has been designed to assess this important domain; it can be used to facilitate patient care and education about vascular access choice and maintenance. AVACS can also be used to inform future research on developing new techniques for AV access creation and maintenance, particularly as relates to AV access cosmesis., Competing Interests: Declaration of Conflicting InterestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The authors declare that they have no conflicts of interest regarding patents or royalties, stock/stock options, or first-degree relatives with any of these relationships related to this work. No reimbursement was received for the development of the manuscript.DR, VN, MM, CR, ED, CG, TV, SH, PB, LD and patients CS, DDR, FM, and MB (see acknowledgements) received remuneration from Becton Dickinson (BD) for their participation in the Delphi process.GW, AH, and NF are employees of CRG-EVERSANA Canada Inc., which was contracted by BD to facilitate the Delphi panel process and analyze the results.EK and DC are employees of the American Association of Kidney Patients (AAKP) which was contracted by BD to advise on patient input and recruited the Patient Ambassadors.DR is a consultant for BD and Gore Medical. VN is a consultant for the NACCME – Moderator for AV Access Webcast, supported by an educational grant from Medtronic. SH is a consultant/speaker for BD, Merit Medical, Medtronic, and Gore Medical. ED is a consultant for WL Gore, Angiodynamics, and 3M/KCI. ED is a scientific advisor for Boston Scientific. TY is a consultant for BD, WL Gore and Merit Medical and a scientific advisory board member of BD and Medtronic. CK is a consultant for BD and ACI/Humacyte and advisory board member for Boston Scientific. CL is a consultant for BD, Gore, and Medtronic.Other ConflictsED, KW, and TY are authors and ED is an editor for UpToDate.

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., Competing Interests: The authors have the following interests: Guillaume JEAN, Patrik DELEAVAL, Christie LORRIAUX, Jean-Marc HUROT, Brice MAYOR, Manolie MEHDI and Charles CHAZOT are employed by NEPHROCARE and Sylvain LECHEVALLIER by CERBALLIANCE. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

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., (Copyright © 2017 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.)

Patients commencing on haemodialysis (HD) have an increased risk of cardiovascular events in the first year after starting HD compared to those patients established on HD longer. Left ventricular (LV) hypertrophy and abnormal myocardial strain predict mortality. There may be changes in the myocardium of incident HD patients over a 6-month period of HD which may explain changes in cardiovascular risk. We used CMR to consider changes in LV mass, myocardial strain and T1 mapping. We examined changes in pre-dialysis highly sensitive troponin T. 33 patients undergoing HD for <12 months were recruited. Participants underwent CMR at baseline and after 6-months of standard care. 6-months of HD was associated with reduction in LV mass index (Baseline: 78.8 g/m 2 follow up: 69.9 g/m 2 , p = <0.001). LV global longitudinal strain also improved (Baseline: -17.9%, follow up: -21.6%, p = <0.001). Change in T1 time was not significant (Baseline septal T1 1277.4 ms, follow up 1271.5 p = 0.504). Highly sensitive troponin T was lower at follow up (Baseline 38.8 pg/L, follow up 30.8 pg/L p = 0.02). In incident HD patients, 6-months of HD was associated with improvements in LV mass, strain and troponin. These findings may reflect improvement in known cardiac tissue abnormalities found in patients over the first year of HD.

Background: Native T1 mapping is a cardiovascular magnetic resonance (CMR) technique that associates with markers of fibrosis and strain in hemodialysis patients. The reproducibility of T1 mapping in hemodialysis patients, prone to changes in fluid status, is unknown. Accurate quantification of myocardial fibrosis in this population has prognostic potential., Methods: Using 3 Tesla CMR, we report the results of 1) the inter-study, inter-observer and intra-observer reproducibility of native T1 mapping in 10 hemodialysis patients; 2) inter-study reproducibility of left ventricular (LV) structure and function in 10 hemodialysis patients; 3) the agreement of native T1 map and native T1 phantom analyses between two centres in 20 hemodialysis patients; 4) the effect of changes in markers of fluid status on native T1 values in 10 hemodialysis patients., Results: Inter-study, inter-observer and intra-observer variability of native T1 mapping were excellent with co-efficients of variation (CoV) of 0.7, 0.3 and 0.4% respectively. Inter-study CoV for LV structure and function were: LV mass = 1%; ejection fraction = 1.1%; LV end-diastolic volume = 5.2%; LV end-systolic volume = 5.6%. Inter-centre variability of analysis techniques were excellent with CoV for basal and mid-native T1 slices between 0.8-1.2%. Phantom analyses showed comparable native T1 times between centres, despite different scanners and acquisition sequences (centre 1: 1192.7 ± 7.5 ms, centre 2: 1205.5 ± 5 ms). For the 10 patients who underwent inter-study testing, change in body weight (Δweight) between scans correlated with change in LV end-diastolic volume (ΔLVEDV) (r = 0.682;P = 0.03) representing altered fluid status between scans. There were no correlations between change in native T1 between scans (ΔT1) and ΔLVEDV or Δweight (P > 0.6). Linear regression confirmed ΔT1 was unaffected by ΔLVEDV or Δweight (P > 0.59)., Conclusions: Myocardial native T1 is reproducible in HD patients and unaffected by changes in fluid status at the levels we observed. Native T1 mapping is a potential imaging biomarker for myocardial fibrosis in patients with end-stage renal disease.

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, β2-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 β2-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., (© 2017 S. Karger AG, Basel.)

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.

Survival of haemodialysis (HD) patients is influenced by many factors. Mortality is mainly of cardiovascular (CV) origin and related to both traditional and nontraditional CV risk factors. Low plasma Beta2-microglobulin (β2m) levels are associated with improved HD patient survival. HD session times that are longer than the conventional 4 h (i.e., extended dialysis) provide better middle molecule clearance and are also associated with a survival advantage. In this crossover randomised trial, we investigated the effect of membrane flux on CV risk factors and on β2m plasma levels in patients treated with extended dialysis. Dialysis session duration was between 5 and 8 h for all patients. Patients were randomly assigned to the treatment sequences low-flux/high-flux dialysis versus high-flux/low-flux dialysis in a crossover design after a 3-month run-in period, with each phase lasting 9 months. Of the initially enrolled 168 patients, 155 patients started the study after the run-in period, 117 patients completed Phase 1, and 83 patients completed the whole study. Lp(a), homocystein, LDL cholesterol, HDL cholesterol and serum albumin were comparable in the low-flux and high-flux treatments. The average β2m level was 43.3 ± 11.1 mg/l at the end of the low-flux phase. Independent of sequence assignation, average β2m was significantly lower at the end of the high-flux phase (27.5 ± 76.0 mg/l, p < 0.0001 versus end of low-flux phase). Both phosphate and nPNA were significantly lower at the end of the high-flux phase compared to the low-flux phase (p = 0.045 and p = 0.002, respectively). Inclusion of those patients who completed Phase 1 and who dropped out of the study during Phase 2 did not significantly change the results. In conclusion, this study did not find an influence of high-flux filters on several traditional CV risk factors in a population of HD patients treated with extended dialysis. However, high-flux filters are necessary to optimise middle molecule clearance and reduce the β2m level., (© 2015 S. Karger AG, Basel.)

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., (2015 S. Karger AG, Basel.)

After creation of an arteriovenous fistula or placement of an arteriovenous graft, several weeks are required for maturation prior to first cannulation. Patients need an alternative way to receive hemodialysis during this time, frequently a catheter. After multiple failed access attempts, patients can run out of options and become catheter dependent. At our institution, we place HeRO grafts in eligible patients who have otherwise been told they would be catheter dependent for life. By combining the HeRO graft system with a Flixene graft, patients are able to remove catheters sooner or avoid placement as they can undergo cannulation for hemodialysis the next day. Utilizing this novel technique, twenty-one patients over a two-year period with various forms of central venous stenosis, catheter dependence, or failing existing arteriovenous access have been successfully converted to stable long term noncatheter based upper extremity access.

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., (© 2014 S. Karger AG, Basel.)

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., (Copyright © 2013 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.)

Background: The target for serum parathyroid (PTH) hormone level in dialysis patients is higher than that in the normal population in order to prevent adynamic bone disease (ABD) that is associated with more frequent cardiovascular and bone disease. Based on biological and clinical data, we aimed at identifying the different types of low PTH (L-PTH) in order to determine the best therapeutic strategies in these patients., Methods: Between 2004 and 2010, all haemodialysis (HD) patients were assessed. Patients with serum L-PTH (<130pg/mL) were classified into five groups as follows : 'PTX' for patients with a history of parathyroidectomy (PTX); 'HypoMed' for patients with a tendency to hypocalcemia without PTX; 'IatroMed' for patients who had undergone excessive PTH-lowering treatments (calcium, vitamin D, or cinacalcet); 'EndoG' for patients with endogenous hypercalcaemia (immobilization, cancer, or granulomatosis); and 'SponT' for patients with L-PTH without evident causes and with 'normal' biology in most cases., Results: From 520 charts, 163 (31.3 %) L-PTH cases were recorded, with 17.7% of PTX in younger patients with longer dialysis times; 2.4% of HypoMed in older women with high co-morbidities (these two groups needed calcium and vitamin D therapy to prevent hypocalcaemia); 22.6% of IatroMed in diabetic patients receiving excessive PTH-lowering treatments; 3% of EndoG in hypercalcaemic patients, more frequently in the hospitalization ward; and 54% of SponT, more frequently comprising old diabetic patients not receiving PTH-lowering treatment and without biological signs of ABD. Treatment changes were necessary only in cases of IatroMed and EndoG, requiring a lowered prescription of PTH-lowering therapies and the addition of bisphosphonates for EndoG., Conclusion: In our HD population, we could identify five types of L-PTH based on medical conditions and biological data. Only two types, i.e. approximately 25% of patients needed therapeutic modifications. For the other patients, L-PTH could be maintained without decreasing the calcium and vitamin D intake that can lead to osteomalacia or administering recombinant PTH 1-34 or calcium-receptor inhibitors that need to be assessed in HD patients., (Copyright © 2012 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.)

Objective: The Kidney Disease: Improving Global Outcomes "KDIGO" recommends regular sampling of bone turnover markers (BTMs) such as total alkaline phosphatases (t-ALP) and bone-specific alkaline phosphatase (b-ALP) in the case of haemodialysis (HD) patients., Design and Methods: We present our results of the regular assessment of t-ALP, b-ALP, and PTH, obtained for existing HD patients with chronic liver disease (LD)., Results: 76 prevalent HD patients were examined. Linear regression showed that b-ALP and t-ALP levels were closely related (r²: 0.6; p<0.0001), even when the serum PTH level was <250 pg/mL (r²: 0.56; p<0.001). The b-ALP/t-ALP ratio was 0.07 ± 0.12 and correlated poorly with PTH levels (r²: 0.03; p=0.01). Both b-ALP and t-ALP levels did not correlated with PTH levels., Conclusion: Our results did not confirm the KDIGO recommendation for using b-ALP as BTM in the special cases of HD patients with LDs., (Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

The diagnosis and treatment of hyperparathyroidism (HPT) are not yet well standardized in chronic renal failure patients. The aim of this study was to identify the main types of HPT on the basis of clinical and biological findings in a haemodialysis population. Between 2004 and 2010, all patients undergoing haemodialysis were observed and treated using the same strategy: conventional therapy with vitamin D supplements, phosphate binders, dialysate calcium adjusted to serum parathyroid hormone (PTH) level and calcitriol analogues (CA), along with regular bone marker analysis. Wherever required, cinacalcet (CC) was administered and parathyroidectomy (PTX) was performed. Of the 520 patients, 158 were classified as having HPT (30%) with a serum PTH level greater than 300 pg/mL. From this population, we identified five main types of HPT: (1) HPT with 'no bone impact' had normal or low bone marker levels (n=28, 17.7%); (2) 'secondary' HPT had elevated bone marker levels, but showed favorable response to CT (n=59, 37.7%); (3) 'tertiary' HPT was accompanied with hypercalcemia and required CC or PTX in case of CT failure (n=11, 6.9%); (4) 'mixed' HPT could not be completely treated with CT and required CC or PTX (n=57, 36%); (5) 'resistant' HPT did not show hypercalcemia, but required PTX after CT and CC failure (n=3, 1.8%). CC was prescribed in 51% cases, CA in 76%, and PTX in 7% of cases. We typified HPT on the basis of physiopathology and stages of HPT progression. Further studies on HPT that focus on bone marker levels are required to establish well-defined treatment strategies. In our study, HPT cases did not show uniform findings in Hémodialyse (HD) patients because of the variation in the stages of the disease at the time of diagnosis., (Copyright © 2011. Published by Elsevier SAS.)

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., (Copyright © 2012 S. Karger AG, Basel.)

Objectives: Brain natriuretic peptide (BNP) is a cardiac peptide secreted by ventricle myocardial cells under stretch constraint. Increased BNP has been shown associated with increased mortality in end-stage renal disease patients. In patients starting haemodialysis (HD), both fluid overload and cardiac history are frequently present and may be responsible for a high BNP plasma level. We report in this study the evolution of BNP levels in incident HD patients, its relationship with fluid removal and cardiac history as well as its prognostic value., Methods: Forty-six patients (female/male: 21/25; 68.6 ± 14.5 years old) surviving at least 6 months after HD treatment onset were retrospectively analysed. Plasma BNP (Chemoluminescent Microparticule ImmunoAssay on i8200 Architect Abbott, Paris, France; normal value < 100 pg/mL) was assessed at HD start and during the second quarter of HD treatment (Q2)., Results: At dialysis start, the plasma BNP level was 1041 ± 1178 pg/mL (range: 14-4181 pg/mL). It was correlated with age (P = 0.0017) and was significantly higher in males (P = 0.0017) and in patients with cardiac disease history (P = 0.001). The plasma BNP level at baseline was not related to the mortality risk. At Q2, predialysis systolic blood pressure (BP) decreased from 140.5 ± 24.5 to 129.4 ± 20.6 mmHg (P = 0.0001) and the postdialysis body weight by 7.6 ± 8.4% (P < 0.0001). The BNP level decreased to 631 ± 707 pg/mL (P = 0.01) at Q2. Its variation was significantly correlated with systolic BP decrease (P = 0.006). A high BNP level was found associated with an increased risk of mortality., Conclusions: Hence, plasma BNP levels decreased during the first months of HD treatment during the dry weight quest. Whereas initial BNP values were not associated with increased mortality risk, the BNP level at Q2 was independently predictive of mortality. Hence, BNP is a useful tool to follow patient dehydration after dialysis start. Initial fluid overload may act as a confounding factor for its value as a prognostic marker because of cardiac disease.

Calciphylaxis (CPX) or calcific uraemic arteriolopathy is a rare life-threatening complication, affecting mainly dialysis patients. The condition is characterized by calcifications and thrombosis of the small cutaneous vessels and small vessels in the fat tissue, resulting in the development of necrotizing and non-healing ulcers. The development of these lesions leads to poor outcomes owing to infectious complications and some frequently associated unfavourable medical conditions: obesity, diabetes, and peripheral vascular disease. We report the case of six patients with different clinical forms of CPX in the past 10 years with favourable outcomes observed in five of the six patients. The diagnosis was based on clinical presentation: bilateral and hyperalgesic necrotic lesions along with a history of mineral metabolism disorder or warfarin use. The therapeutic strategy included the following: daily dialysis, hyperbaric oxygen therapy, treatment of limb artery stenosis, maintenance of the optimal haemodynamic stability, delivery of cutaneous care, administration of analgesics and antibiotics, warfarin and calcium cessation, and additional therapy with cinacalcet or parathyroidectomy and therapy with bisphosphonates or sodium thiosulphate. Healing was observed in five out of six CPX patients by using this strategy that should be rapidly employed in order to decrease the necrotizing areas that result in poor outcomes. Prevention includes identification of at-risk patients in order to optimize the treatment of the identified risk factors for CPX., (Copyright © 2010 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.)

Introduction: The treatment of secondary hyperparathyroidism (SHPT) in dialysis patients has changed with the introduction of cinacalcet (CC), which represents a medical alternative to surgical parathyroidectomy (PTX). The aim of our study is to prospectively assess the tolerance and efficacy of CC in patients, treated in one centre using long haemodialysis, with SHPT who do not respond to conventional therapy., Patients and Methods: We prospectively observed all patients treated with CC between September 2004 and 2009. The characteristics of the patients were compared with that recorded for the patients non treated with CC. Biological factors and the efficacy of the treatment in the patients were compared before (T-0) and after (T-End) CC therapy. The haemodialysis (HD) schedule was 3 x 5 to 3 x 8 h per week. The biological criteria for CC prescription were a serum PTH level greater than 300 pg/ml, calcium level greater than 2.45 mmol/l and bone alkaline phosphatase level greater than 20 microg/l or, in cases of tertiary hyperparathyroidism (THPT), a calcium level greater than 2.55 mmol/l., Results: Eighty-one (14.7%) among the 550 HD patients were treated with CC. As compared to the untreated population, these patients were younger and had higher body mass index (BMI) and higher protein-catabolic rate (nPCR). The treatment failed in 6.1% of the treated patients; 12.3% had severe gastrointestinal side effects and 10% underwent PTX. The treatment was successful in 81.4% patients who were prescribed a mean final CC dosage of 51+/-30 mg/day. Between T-0 and T-End (18+/-15) months), the serum PTH levels decreased by 77%, calcaemia levels decreased by 10% and phosphataemia levels decreased by 14%. Therefore, the percentage of patients with normal biological parameters increased significantly : serum PTH (150-300 pg/ml: 0 to 50%), calcaemia (2.1-2.37 mmol/l: 6 to 77%) and phosphataemia (1.15-1.78 mol/l: 58 to 84%). After 12 months, eight patients (10%) successfully weaned from CC therapy. No episodes of hypocalcaemia (<2.0 mmol/l) occurred. Treatments with alfacalcidol (68 to 40%) and sevelamer (72 to 50%) decreased, treatments with CaCO(3) remained stable (20%), those with native vitamin D increased (55 to 95%)., Conclusion: The treatment of HD patients having SHPT and THPT with CC and vitamin D derivatives was efficacious and well tolerated in a majority of cases after the failure of conventional therapies. These treatments improved mineral metabolism significantly., (Copyright 2010 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.)

In hemodialysis (HD) patients, mineral metabolism (MM) disorders have been associated with an increased mortality rate. We report the evolution of MM parameters in a stable HD population undergoing long hemodialysis by performing an annual cross-sectional analysis for every year from 1994 to 2008. The therapeutic strategy has changed: the dialysate calcium concentration has decreased from a mean of 1.7 +/- 0.1 to 1.5 +/- 0.07 mmol/L and has been adapted to parathyroid hormone serum levels (from 1 to 1.75 mmol/L). The use of calcium-based and aluminum-based phosphate binders has decreased and they have been replaced by sevelamer; alfacalcidol has partly been replaced by native vitamin D. The percentage of patients with a parathyroid hormone serum level between 150 and 300 pg/mL has increased from 9% to 67% (P<0.001); the percentage of patients with phosphataemia between 1.15 and 1.78 mmol/L has increased from 39% to 84% (P<0.001). The percentage of those with albumin-corrected calcemia between 2.1 and 2.37 mmol/L has increased from 29% to 61% (P<0.001), and that of patients with a calcium-phosphorous product (Ca x P) level >4.4 mmol/L decreased from 8.8% to 2% (P=0.02). Although patients undergo long and intensive HD treatment, MM disorders are common. However, an appropriate strategy, mostly consisting of native vitamin D supplementation, progressive replacement of calcium-based phosphate binders with non-calcium-based ones, and individualization of dialysis session duration and dialysate calcium concentration, would result in a drastic improvement.

Background: Fibroblast growth factor (FGF)-23, a novel bone-derived phosphaturic factor involved in mineral metabolism, is increased in chronic kidney disease (CKD); in dialysis patients, it has been linked to increased mortality rates and vascular calcification (VC). The present investigation aimed to study the factors associated with elevated serum FGF-23 levels in patients treated with long haemodialysis (LHD) sessions and to determine whether a relationship exists between serum FGF-23 levels and patient survival., Methods: All patients treated in one haemodialysis centre from September 2006 were included in the study. Standard laboratory values, medical history, cardiovascular events and risk factors, medication and FGF-23 levels [ELISA (C-Term) Immutopics] were recorded. Patients received haemodialysis three times a week, on a 5- to 8-h schedule. Patient data were analysed according to FGF-23 quartiles. The effect of FGF-23 on the 2-year survival rate was assessed using the Cox proportional hazard model, adjusted for confounding variables and according to the serum phosphate tertiles., Results: The study included 219 patients. Serum FGF-23 levels were high: 7060 +/- 13 500 RU/mL (median, 2740 RU/mL). In logistical regressions, only calcaemia (P = 0.002), phosphataemia (P = 0.008) and warfarin use (P = 0.04) were associated with the highest FGF-23 quartile. In the subgroup of patients with an estimated VC score, the third and fourth quartiles of the FGF-23 levels were associated with more severe VC. In multivariate linear regressions, only phosphataemia remained significantly correlated with FGF-23 (P = 0.04). The 2-year mortality rate was significantly higher for haemodialysis patients with serum FGF-23 levels in the higher quartile [P = 0.007; hazard ratio, 2.5 (1.3-5)] than in the first quartile, whereas within the phosphataemia tertiles, the lowest serum FGF-23 quartile was associated with lowered mortality., Conclusion: This study demonstrated a high level of circulating FGF-23 in LHD patients, despite infrequent hyperphosphataemia. However, phosphataemia is still the main factor correlating with serum FGF-23. The association of higher serum FGF-23 levels with mortality and VC, regardless of the serum phosphate levels, has thus been confirmed.

Introduction: Catheter-related adverse events (CAE) remain a major cause of mortality and morbidity., Aim: We aimed to compare the CAE prevalence and adverse events rate at 10 years interval in one centre using different devices, dressing procedures., Methods: We compared two periods, from 1994 to 1997 (period 1) and from 2004 to 2007 (period 2). We recorded all prevalent tunnelled CAE and their related adverse event rate: catheter-related bacteraemia (CRB), catheter local infection (CLI), catheter dysfunction leading to CAE exchange, thrombolytic use and spontaneous pulling up., Results: In period 1, PermCath catheter (Quinton, N=63) and TwinCath catheter (MedComp, N=76) were used in 95 HD. BioFlex catheter (N=52) and ASPC split catheter (MedComp, N=52) were used in 72 HD in period 2. In period 1, we performed catheter dressing using povidone iodine versus alcoholic chlorexidine in period 2. Between period 1 and period 2, the CAE prevalence decreased from 15-18% to 9-6%, CRB from 1.1 to 0.23/1000 day-catheter (p<0.001), CLI from 1.1 to 0.28/1000 day-catheter (p<0.001), definitive dysfunction from 12 to 1.2% (p<0.001) and CAE pulling up from 4 to 0%. The annual urokinase consumption decreased from three to one unit per CAE., Conclusion: This study shows the dramatic decrease in CAE prevalence (-50%) and related-adverse events (approximately -200%) since 10 years. Switching povidone iodine to chlorexidine and using more recent catheter devices appear very efficient in decreasing catheter-related adverse events.

Background: Vascular calcifications (VCs) are frequently observed in chronic kidney disease (CKD) and haemodialysis (HD) patients. They have been associated with numerous factors, particularly hyperphosphataemia, excess calcium load, hypertension and increased mortality rate. The purpose of this study is to measure VCs in long-HD patients with good blood pressure and phosphate control, with the occasional use of sevelamer, using a plain radiological score to identify the associated factors and effects on the 1-year survival rate., Methods: We studied HD patients from one centre using a semi-quantitative score ranging from 0 to 3 according to the severity and extent of VCs. The following patients' characteristics were compared according to their VC scores: medical history, treatments, blood pressure, standard biological data, fibroblast growth factor (FGF) 23, osteoprotegerin (OPG), whole PTH, beta-crosslaps, bone alkaline phosphatases and bone mineral density scores. One-year survival analyses were also performed., Results: Among the 250 HD patients of the centre, 161 were studied; the mean age was 67.2 +/- 13 years, 45% of the subjects were females, 35% were diabetics, and they had been on dialysis for between 1-486 months (median: 45 months) with a 3 x 5-3 x 8 h dialysis schedule using 1.5 mmol/l dialysate calcium and providing a mean 2.25 +/- 0.5 Kt/V. Only 17% of the patients were free from VCs and 11% had severe VCs. The factors associated with VCs were classified into 'classic' (age, diabetes, male gender, tobacco use, inflammation, more frequent warfarin treatment and peripheral vascular and cardiac diseases) and 'non-traditional' (higher FGF-23 and OPG serum levels, low albumin serum levels and low alfacalcidol and CaCO(3) use). In logistic regression, only age, diabetes and FGF-23 serum levels were associated with VC scores of 2 and 3. The patients with a score of 3 had a higher 1-year mortality rate (RR 2.1; P = 0.01) as compared to patients with a 0 score., Conclusion: A plain radiological score showed the high prevalence (83%) of VCs in HD patients in spite of a long and intensive dialysis strategy and adherence to guidelines. The main associated factors were classic factors such as ageing and diabetes. No relationship was found with blood pressure and phosphataemia that remained well controlled in long dialysis; the association with FGF-23 serum levels may aggregate some non-traditional risk factors. The harmful effects of VCs on survival require their systematic assessment and optimization of the potentially modifiable associated factors in CKD and HD patients.

Background: In hemodialysis (HD) patients, the plasma brain natriuretic peptide (BNP) level is associated with left ventricular dysfunction and patients' survival. Malnutrition is common in HD patients, it is associated with inflammation and contributes to the high incidence of cardiovascular (CV) disease in this setting (malnutrition-inflammation-atherosclerosis syndrome). In a cross-sectional study, we assessed the relationship between predialysis plasma BNP level and nutritional markers in chronic HD patients., Methods: Of 210 patients receiving HD treatment in our unit, 51 patients who were treated with three times weekly long-hour HD (5-8 h/session) for at least 6 months (mean age 65.8 +/- 15.0 years; F/M ratio 23/28; vintage 71.3 +/- 71.9 months; BMI 24.9 +/- 5.9; session time 6.9 +/- 1.3 h; percentage of diabetic patients 31%) were studied before a mid-week HD session for nutritional markers (plasma albumin 35.3 +/- 3.7 g/l; prealbumin 0.36 +/- 0.09 g/l; CRP 15.3 +/- 14.7 mg/l; nPNA 1.29 +/- 0.29 g/kg/day) and plasma BNP (246.9 +/- 252.2 ng/l, normal <100 ng/l, Bayer(R) kit). The interdialytic weight gain was 2.1 +/- 1.0 kg. In the last 3 months prior to the commencement of the study, the patients' dry weight varied by +0.17 +/- 1.9 kg., Results: Predialysis plasma BNP levels did not differ according to gender and the presence of diabetes. It was not correlated with age and vintage but was found to be negatively associated with the session time (r = -0.34, p = 0.018). Several nutritional markers were negatively correlated with BNP levels: prealbumin (r = -0.46, p = 0.001), BMI (r = -0.33, p = 0.018), nPNA (r = -0.46, p = 0.002). The plasma albumin relationship with the BNP level was close to significance (p = -0.26, p = 0.070). The 3-month dry weight variation was also negatively correlated with BNP levels (r = -0.34, p = 0.018). With multiple stepwise regression analysis, prealbumin and session time remained significant (respectively p = 0.004 and 0.01). BNP levels were higher in a subgroup of malnourished patients (n = 12) (400 +/- 405 vs. 202 +/- 166 ng/l, p = 0.03) than in patients who did not meet the malnutrition criteria (34 patients). They were not correlated with CRP levels, interdialytic weight gain, or predialysis MAP., Conclusions: Hence, the plasma BNP level was found to be associated with malnutrition but not with inflammation. This underlines the relationship between nutrition and the CV system in HD patients. The body weight variations associated with malnutrition and the difficulties in assessing and adjusting dry weight may lead to fluid overload, which could explain, in part, these correlations., (Copyright 2009 S. Karger AG, Basel.)

Background: Vitamin D deficiency is frequently observed in end-stage renal disease (ESRD) patients; however, the effects of vitamin D supplementation have rarely been reported. We aimed to assess the effects of daily 25(OH)D(3) supplementation on mineral metabolism, bone markers and Kidney Disease Outcomes Quality Initiative (KDOQI) targets in haemodialysis (HD) patients for a period of 6 months., Methods: HD patients were included in this study if their serum 25(OH)D level was <75 mmol/L. Oral 25(OH)D(3) was administered daily at 10-30 microg/day based on the severity of the deficiency. Characteristics of the patients were compared from the baseline to 6 months on the basis of their response to 25(OH)D(3) administration and the patients were divided into three groups. Patients who showed partial response [serum 25(OH)D <75 nmol/L] were placed in group 1, those who showed normal response [serum 25(OH)D ranging from 75 to 150 nmol/L] were placed in group 2 and those who showed excessive response [serum 25(OH)D >150 nmol/L] were placed in group 3., Results: Of the 253 HD patients, 225 (89%) showed vitamin D insufficiency or deficiency, 172 were included in the study and 149 patients completed the study. After 6 months of treatment [mean daily 25(OH)D(3): 16 +/- 5 microg/day], the serum 25(OH)D level increased (30 +/- 19 to 126 +/- 46 nmol/ L, P < 0.001), with 13% of patients in group 1, 57% in group 2 and 30% in group 3. The serum intact parathyroid hormone (iPTH) level decreased (235 +/- 186 to 189 +/- 137 pg/mL, P = 0.05), except in group 1. Bone alkaline phosphatase (BALP) showed a tendency to normalize (23 +/- 16 to 18.3 +/- 11 microg/L, P < 0.05), leading to a decrease in alfacalcidol administration from 66% to 43% (P < 0.05), except in group 1. The KDOQI targets achieved increased significantly for serum calcium (76% to 85%) and phosphate levels (66% to 77%) in all patients. The serum albumin level increased in all groups (34.6 +/- 4 to 36.8 +/- 4 g/L, P < 0.05), without any significant improvement in normalized protein catabolic rate (nPCR) or C-reactive proteins (CRP)., Conclusion: With a daily dose ranging from 10 to 30 microg, daily oral 25(OH)D(3) supplementation corrects most vitamin D deficiencies or insufficiencies in HD patients, without any evident toxicity. The main effects observed included correction of excessive bone turnover, despite less alfacalcidol administration, increase in serum albumin level and increase in the percentage of patients with serum calcium and phosphorus levels within the recommendation of the KDOQI guidelines.