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.

[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.

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.

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.

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.

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.

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.

[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.

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.

Increased levels of serum parathyroid hormone and fibroblast growth factor-23 are the main factors associated with the progression of vascular calcification in long-hour hemodialysis patients.

The aim of the present study was to assess the frequency and factors associated with the progression of vascular calcifications (VCs) using a semiquantitative X-ray score. We included all prevalent hemodialysis patients with initial radiological scores ranging from 0 to 3 according to the severity of the VCs. Patients were classified as non-progressors or progressors after 3 years. Among the 85 patients, 44.7% were classified as progressors. Only exhibiting high levels of serum intact parathyroid hormone (PTH, >190 pg/ml) and fibroblast growth factor (FGF)-23 levels (>3,000 RU/ml) is associated with the risk of VC progression (OR 5.8, 95% CI 1.7-19.8, p = 0.004). Calcitriol analogs (38%), cinacalcet (15%), dialysate calcium (mean 1.48 mmol/l), dialysis session time (4-8 h) and calcium- (10%) and non-calcium-based phosphate binders (38%) were prescribed on an individual basis. Hyperphosphatemia (<10%) and, especially, hypercalcemia (1%) and hyperparathyroidism (>585 pg/ml = 0%) were infrequently observed. In conclusion, the main factor associated with VC progression was the association of higher serum PTH and FGF-23 levels. It remains to be seen whether patients should be treated to lower their PTH value, even within the target range, using calcitriol analogs, calcimimetics, parathyroidectomy, or by modifying the Klotho-FGF-23 axis.

[How to deal with those low parathyroid hormone values in dialysis patients?]. / Que faire de ces valeurs d'hormones parathyroïdiennes réputées trop basses chez les patients dialysés ?

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.

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.

Total and bone-specific alkaline phosphatases in haemodialysis patients with chronic liver disease.

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.

[Clinical and biological forms of secondary hyperparathyroidism in dialysis patients]. / Les formes cliniques et biologiques de l'hyperparathyroïdie secondaire en dialyse.

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.

Fluid overload correction and cardiac history influence brain natriuretic peptide evolution in incident haemodialysis patients.

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 in dialysis patients: To recognize and treat it as soon as possible]. / La calciphylaxie chez le patient dialysé : la reconnaître pour la traiter aussitôt que possible.

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.

[Treatment of secondary hyperparathyroidism resistant to conventional therapy and tertiary hyperparathyroidism with Cinacalcet: an efficiency strategy]. / Traitement de l'hyperparathyroïdie secondaire, résistante aux thérapeutiques conventionnelles, et de l'hyperparathyroïdie tertiaire par le cinacalcet: une stratégie efficace.

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.

Treating mineral metabolism disorders in patients undergoing long hemodialysis: a search for an optimal strategy.

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.