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.

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.

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.

[Dialysis monitoring: peritoneal equilibrium test, regional citrate anticoagulation and residual renal function]. / Suivi de la dialyse : test d'équilibration péritonéale, anticoagulation régionale au citrate, et fonction rénales résiduelle.

The SFBC working group aimed to deal with biological tests outside the French nomenclature that may be useful for the follow-up of dialysis patients. Our discussion was divided into 3 parts: 1) evaluation of peritoneal membrane characteristics; 2) monitoring of renal replacement therapy using regional citrate anticoagulation; 3) estimation of residual renal function (RRF). International recommendations underline the importance of assessing peritoneal membrane characteristics for peritoneal dialysis prescription. This peritoneal equilibrium test requires the measurement in dialysate of the following parameters: glucose, urea, creatinine and sodium. As part of the monitoring of continuous renal replacement therapy using regional citrate anticoagulation, the determination of ionized calcium assay is essential according to national and international guidelines to ensure a balance between effective anticoagulation and appropriate calcium levels. Finally, the RRF plays a key role in the dialysis adequacy and patient survival. European and international recommendations highlight the potential interest of RRF in peritoneal dialysis and hemodialysis. The RRF corresponds to the mean of urinary urea and creatinine clearance, assessed from a urine collection with measurement of urinary urea.

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.

High Serum Sclerostin Levels Are Associated with a Better Outcome in Haemodialysis Patients.

BACKGROUND: Sclerostin is an osteocyte hormone that decreases osteoblastogenesis. Sclerostin may play a key role in osteoporosis and also in vascular calcification (VC). In chronic kidney disease and haemodialysis (HD) patients, serum sclerostin levels are high. AIM: To assess the correlation of serum sclerostin levels with VC, bone mineral density (BMD), and survival rate in HD patients. METHODS: A cross-sectional study was conducted in prevalent HD patients to correlate serum sclerostin tertiles with the Kauppila aortic calcification score, BMD scores and survival rate. RESULTS: We studied 207 patients who had a mean serum sclerostin level of 1.9 ± 0.7 ng/ml. Compared to patients in the 1st tertile of serum sclerostin levels (0.6-1.53 ng/ml), patients in the 3rd tertile (2.2-4.6 ng/ml) were significantly older (73.7 ± 12 vs. 64.7 ± 18 years), more frequently of the male gender (74 vs. 48%), had lower serum bone-specific alkaline phosphatases values (14 ± 9 vs. 20.4 ± 13 µg/l), were less frequently treated with alfacalcidol, displayed lower aortic calcification scores (9.5 ± 5 vs. 12.5 ± 7/24) and had higher BMD scores. Furthermore, patients of the 3rd tertile displayed a lower mortality rate compared to tertile 1 using multivariable adjusted Cox model (hazard ratio 0.5, 95% CI 0.25-0.93, p = 0.03). The main factors associated with VC score were age, diabetes, cardiovascular disease, CRP level and Warfarin use. CONCLUSION: Our study of HD patients shows that higher serum sclerostin levels are associated with higher BMD, lower aortic calcification scores, and a better survival rate.

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.

Effect of Membrane Permeability on Cardiovascular Risk Factors and ß2m Plasma Levels in Patients on Long-Term Haemodialysis: A Randomised Crossover Trial.

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 (ß2m) 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 ß2m 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 ß2m level was 43.3 ± 11.1 mg/l at the end of the low-flux phase. Independent of sequence assignation, average ß2m 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 ß2m level.

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.