European Hemodialysis Patients Research Articles

Chronic kidney disease-associated pruritus: a comparison of instruments and associations with patient-reported outcomes using an electronic patient-reported outcome survey in Europe.

The associations between self-reported chronic kidney disease-associated pruritus (CKD-aP) and patient-reported outcomes (PROs) have been reported using various instruments to assess itch. Data collection via multiple CKD-aP instruments allows the evaluation of different domains and measurements of CKD-aP burden and may help tailor data capture for future research or clinical care. An electronic PRO (ePRO) survey was distributed to European hemodialysis (HD) patients enrolled in the Dialysis Outcomes and Practice Patterns Study (DOPPS) in 2021-23. The DOPPS is an international cohort study that aims to investigate practice patterns and outcomes in HD patients. The ePRO survey included multiple CKD-aP instruments: Average Itch and Worst Itching Intensity Numerical Rating Scales (AI-NRS, WI-NRS) and a Kidney Disease Quality of Life (KDQOL)-36 single question. Linear and logistic regression were used to estimate adjusted associations between CKD-aP instruments and various PROs. This analysis included 769 patients who completed the WI-NRS from HD facilities in France, Germany, Italy, Spain, Sweden and the UK. The correlation between WI-NRS and the KDQOL-36 itch question was 0.88 overall and 0.46 among patients at least somewhat bothered by itch. Mean WI-NRS scores stratified by response to the KDQOL-36 itch question were 8.1, 6.4, 4.1 and 3.1 for extremely, very much, moderately and somewhat bothered, respectively. Patients with worse WI-NRS scores reported worse sleep quality, greater fatigue, more depressive symptoms, and lower mental and physical quality of life; these associations were similar to those observed for the KDQOL-36 itch question. Correlation between CKD-aP instruments was high overall, but moderate among the subgroup of patients bothered by itch; differences can be partially attributed to the recall period for the KDQOL-36 (4 weeks) vs the AI- and WI-NRS (24 h). The consistent associations of these instruments with poor outcomes underscores the importance to identify and effectively treat HD patients suffering from pruritus.

MO792CONTEMPORARY MINERAL AND BONE DISORDER MARKERS AND TREATMENT AMONG HEMODIALYSIS PATIENTS IN THE EUROPEAN DIALYSIS OUTCOMES AND PRACTICE PATTERNS STUDY (DOPPS)*

Abstract Background and Aims Chronic kidney disease mineral and bone disorder (CKD-MBD) is characterized by abnormalities in serum calcium, phosphorus, and parathyroid hormone (PTH) and associated with morbidity and mortality. Previous publications from the Dialysis Outcomes and Practice Patterns Study (DOPPS) have demonstrated country differences in the prevalence and treatment of CKD-MBD among hemodialysis patients in participating European countries. We aim to compare the distribution of CKD-MBD related labs and treatments across countries in a contemporary population of European hemodialysis patients. Method DOPPS is an international prospective cohort study of hemodialysis patients ≥18 years of age. Patients are enrolled randomly from a representative sample of dialysis facilities within each nation at the start of each study phase. The current analysis includes n=1,701 patients from 91 facilities in the initial prevalent cross section of Europe DOPPS phase 7 (2019-present; Belgium, Germany, Italy, Spain, Sweden, UK). Results from Belgium should be considered preliminary as initial questionnaire completion is ongoing. Results The % of patients with a high PTH (>600 pg/mL) ranged from 6% in Italy to 24% in the UK, with 12-17% having high PTH in all other countries. Mean serum total calcium ranged from 8.7 in Germany to 9.1 mg/dL in the UK (Table). Mean serum phosphorus varied from 4.5 in Belgium to 5.3 mg/dL in Germany. Dialysate calcium of 2.5 mEq/L was predominant in Germany, Sweden, and the UK while 3.0 mEq/L was the most common prescription in Belgium, Italy, and Spain. Calcimimetic prescription ranged from 13% in the UK to 32% in Spain. Etelcalcetide prescription ranged from 1% in the UK to 12% in Spain and 14% in Italy. Active vitamin D prescription ranged from 27% in Belgium to 75% in Sweden. Nearly all vitamin D prescriptions were administered intravenously in Spain versus about half in Italy; in all other countries, the route of active vitamin D administration was primarily oral. Patient age and dialysis vintage varied by country, potentially contributing to some of the observed country differences in MBD marker levels and treatment practices. Conclusion CKD-MBD related abnormalities in PTH, serum phosphorus and calcium remain common in European dialysis patients, with prevalence varying considerably by country. Substantial international variation in CKD-MBD treatments was also observed in prescription of vitamin D and calcimimetics. Uptake of the relatively new calcimimetic, etelcalcetide, varied considerably by country. A detailed understanding of the effect of treatment variation on CKD-MBD marker levels and patient outcomes is needed to provide important insights for the European HD community in optimizing management of secondary hyperparathyroidism.

Time-dependent lipid profile inversely associates with mortality in hemodialysis patients - independent of inflammation/malnutrition.

Patients with end-stage kidney disease have an extremely high cardiovascular mortality rate, but there is a paradoxical relationship between lipid profile and survival in haemodialysis patients. To investigate whether inflammation/malnutrition confounds the associations between lipids and mortality, we studied a full lipid profile comprising of five clinically well-established lipid parameters and its associations with mortality in a large, multinational European cohort with a median follow-up >3years. The association between quartiles of total, high-density lipoprotein (HDL), non-HDL, low-density lipoprotein (LDL) cholesterol, as well as triglyceride, levels and the end-points of all-cause, cardiovascular and non-cardiovascular mortality was assessed in a cohort of 5,382 incident, adult haemodialysis patients from >250 Fresenius Medical Care dialysis centres out of 14 participating countries using baseline and time-dependent Cox models. Analyses were fully adjusted and stratified for inflammation/malnutrition status and other patient-level variables. Time-dependent quartiles of total, HDL, non-HDL and LDL cholesterol were inversely associated with the hazard for all-cause, cardiovascular and non-cardiovascular mortality. Compared with the lowest quartile of the respective lipid parameter, hazard ratios of other quartiles were <0.86. Similar, albeit weaker, associations were found with baseline lipid profile and mortality. Neither time-dependent nor baseline associations between lipid profile and mortality were affected by inflammation/malnutrition, statin use or geography. Baseline and time-dependent lipid profile are inversely associated with mortality in a large, multicentre cohort of incident haemodialysis patients. Inflammation/malnutrition is not a confounder nor effect modificator of the associations between lipid profile and mortality in European haemodialysis patients.

Estimating hospital inpatient cost-savings with sucroferric oxyhydroxide in patients on chronic hemodialysis in five European countries: a cost analysis

Aims Hyperphosphatemia is common among patients with advanced chronic kidney disease (CKD) undergoing dialysis. The iron-based phosphate binder (PB), sucroferric oxyhydroxide (SO), has a low daily pill burden and is indicated for the control of serum phosphorus in these patients. In a retrospective database study, hemodialysis patients switched to long-term SO therapy had fewer hospitalizations compared with patients switched to other PB therapies. This economic analysis aimed to quantify potential cost-savings of reduced hospitalizations associated with SO for healthcare systems in five European countries. Materials and methods All-cause hospital admissions incidence data were sourced from a real-world retrospective database study comparing adult, in-center hemodialysis patients maintained on 2 years of SO therapy (mSO) versus patients who discontinued SO (dSO) within 90 days of their first prescription and switched to other PBs. A literature search was conducted to determine the cost per hospital admission for dialysis patients in the healthcare setting of each European country. A cost-model combined the incidence rate of all-cause hospital admissions and the cost per admission to estimate the country-specific inpatient costs for the mSO and dSO groups. Results Annual inpatient cost-savings per patient in the mSO group versus the dSO group were €1,201, €2,097, €2,059, €1,512, and €3,068 in France, Germany, Italy, Spain, and the UK, respectively. When annual PB drug costs per patient were considered, the net annual economic cost-savings per patient were €327, €1,585, €1,022, €1,100, and €2,204, respectively. Limitations Hospital admissions data used in the analysis were observational in nature and derived from a US hemodialysis patient population; the effect of SO therapy on hospitalization rates for US and European hemodialysis patients may differ. The analysis did not consider indirect healthcare costs associated with hospitalizations. Conclusion SO therapy may offer substantial inpatient cost-savings by reducing all-cause hospital admissions attributable to uncontrolled hyperphosphatemia.

The real-world effectiveness of sucroferric oxyhydroxide in European hemodialysis patients: a 1-year retrospective database analysis

BackgroundThe iron-based phosphate binder (PB), sucroferric oxyhydroxide (SFOH), demonstrated its effectiveness for lowering serum phosphate levels, with low daily pill burden, in clinical trials of dialysis patients with hyperphosphatemia. This retrospective database analysis evaluated the real-world effectiveness of SFOH for controlling serum phosphate in European hemodialysis patients.MethodsDe-identified patient data were extracted from a clinical database (EuCliD®) for adult hemodialysis patients from France, Italy, Portugal, Russia and Spain who were newly prescribed SFOH for up to 1 year as part of routine clinical care. Serum phosphate and pill burden were compared between baseline (3-month period before starting SFOH) and four consecutive quarterly periods of SFOH therapy (Q1−Q4; 12 months) in the overall cohort and three subgroups: PB-naïve patients treated with SFOH monotherapy (mSFOH), and PB-pretreated patients who were either switched to SFOH monotherapy (PB → mSFOH), or received SFOH in addition to another PB (PB + SFOH).Results1096 hemodialysis patients (mean age: 60.6 years; 65.8% male) were analyzed, including 796, 188 and 53 patients in, respectively, the PB + SFOH, mSFOH, and PB → mSFOH groups. In the overall cohort, serum phosphate decreased significantly from 1.88 mmol/L at baseline to 1.77–1.69 mmol/L during Q1–Q4, and the proportion of patients achieving serum phosphate ≤1.78 mmol/L increased from 41.3% at baseline to 56.2–62.7% during SFOH treatment. Mean PB pill burden decreased from 6.3 pills/day at baseline to 5.0–5.3 pills/day during Q1–Q4. The subgroup analysis found the proportion of patients achieving serum phosphate ≤1.78 mmol/L increased significantly from baseline during SFOH treatment in the PB + SFOH group (from 38.1% up to 60.9% [Q2]) and the mSFOH group (from 49.5% up to 75.2% [Q2]), but there were no significant changes in the PB → mSFOH group. For the PB + SFOH group, serum phosphate reductions were achieved with a similar number of PB pills prescribed at baseline prior to SFOH treatment (6.5 vs 6.2 pills/day at Q4). SFOH daily pill burden was low across all 3 subgroups (2.1–2.8 pills/day).ConclusionIn this real-world study of European hemodialysis patients, prescription of SFOH as monotherapy to PB-naïve patients, or in addition to existing PB therapy, was associated with significant improvements in serum phosphate control and a low daily pill burden.

Changes in pre-dialysis blood pressure variability in the first year of dialysis associate with mortality in European hemodialysis patients: a retrospective cohort study on behalf of the MONDO Initiative.

Pre-hemodialysis systolic blood pressure variability (pre-HD SBPV) has been associated with outcomes. The association of a change in pre-HD SBPV over time with outcomes, and predictors of this change, has not yet been studied. Therefore, we studied this in a cohort of 8825 incident hemodialysis (HD) patients from the European Monitoring Dialysis Outcomes Initiative database. Patient level pre-HD SBPV was calculated as the standard deviation of the residuals of a linear regression model of systolic blood pressure (SBP) over time divided by individual mean SBP in the respective time periods. The pre-HD SBPV difference between months 1-6 and 7-12 was used as an indicator of pre-HD SBPV change. The association between pre-HD SBPV change and all-cause mortality in year 2 was analyzed by multivariate Cox models. Predictors of pre-HD SBPV change was determined by logistic regression models. We found the highest pre-HD SBPV tertile, in the first 6 months after initiation of HD, had the highest mortality rates (adjusted HR 1.44 (95% confidence intervals (95% CI): 1.15-1.79)). An increase in pre-HD SBPV between months 1-6 and 7-12 was associated with an increased risk of mortality in year 2 (adjusted HR 1.29 (95% CI: 1.05-1.58)) compared with stable pre-HD SPBV. A pre-HD SBPV increase was associated with female gender, higher mean pre-HD SBP and pulse pressure, and lower HD frequency.

SO073IRON-RELATED PARAMETERS AND ANTI-ANAEMIC THERAPY IN HAEMODIALYSIS PATIENTS TREATED WITH SUCROFERRIC OXYHYDROXIDE: A 1-YEAR RETROSPECTIVE EUROPEAN CLINICAL DATABASE (EUCLID) ANALYSIS

Abstract Background and Aims This retrospective analysis of data from the European Clinical Database (EuCliD®) evaluated changes in iron-related parameters and use of concomitant anti-anaemic therapies in European haemodialysis (HD) patients treated with sucroferric oxyhydroxide (SFOH). Previous Phase 3 clinical studies and non-clinical studies have indicated that there is minimal iron absorption from SFOH. This study aimed to evaluate the changes in iron-related parameters among patients treated with SFOH in the real-world setting. Method De-identified patient data were extracted from a clinical database (EuCliD®) for adult HD patients newly prescribed SFOH routinely for up to 1 year (1 Jan 2015–1 Jan 2019). Levels of serum ferritin, transferrin saturation (TSAT) and haemoglobin were compared between baseline (BL; 3-month period before starting SFOH) and each quarterly period in the year after starting SFOH treatment (Q1–Q4). Proportions of patients receiving intravenous (IV) iron and erythropoiesis-stimulating agent (ESA) therapies, in addition to their mean weekly doses, during each quarter were recorded. Results The cohort included 1,096 patients with recorded SFOH prescriptions (mean age: 60.6 years; 65.8% male). There were small, but significant increases in ferritin from BL to Q1–Q4 (P&amp;lt;0.05 for all periods vs BL). There were also increases in TSAT (P&amp;lt;0.05 at Q1 and Q2 vs BL) and haemoglobin (P&amp;lt;0.001 at Q1 and Q3 vs BL) (Table). During the 1-year SFOH treatment period, the proportion of patients receiving IV iron therapy decreased (P&amp;lt;0.05 at Q2 and Q3 vs BL) and there was a significant reduction in the mean weekly dose of IV iron administered (P&amp;lt;0.05 at Q2 and Q3 vs BL). The use of ESA therapy also declined (P&amp;lt;0.05 at Q3 and Q4) and there was a significant decrease in the mean weekly dose of ESA during the 1-year SFOH follow-up period (P&amp;lt;0.05 for all periods vs BL). Conclusion This real-world study showed that SFOH treatment in routine clinical practice for up to 1 year was associated with small increases in iron-related parameters and decreases in the use and mean dose of concomitant anti-anaemic therapies in European HD patients. The results from this study indicate that SFOH treatment may be associated with the reduction in concomitant IV iron and ESA use in HD patients, in line with previous findings from the Phase 3 study.

Cinacalcet-induced hypocalcemia in a cohort of European haemodialysis patients: predictors, therapeutic approaches and outcomes

BackgroundCalcimimetic treatment of secondary hyperparathyroidism in chronic dialysis patients is often followed by hypocalcemia.MethodsWe investigated the frequency, predictors, consequences and therapeutic responses following cinacalcet-induced hypocalcemia in an incident European hemodialysis cohort of 1068 patients with a cinacalcet prescription.ResultsOf 905 normocalcemic patients initiating cinacalcet, 67% developed hypocalcemia within 12 months: 68% mild, 23% moderate, 9% severe. Compared to persistently normocalcemic patients, those with severe hypocalcemia were more often diabetic, overweight, had cardiovascular disease, shorter dialysis vintage, used a catheter dialysis access, had fewer active vitamin-D sterols, and exhibited higher CRP and iPTH and lower calcium levels. Multivariate predictors of hypocalcemia included a catheter for vascular access, low albumin and high iPTH. Generally, no therapeutic intervention to prevent hypocalcemia was taken prior to cinacalcet initiation. After the hypocalcemic event, the most common clinical response was no change of the dialysis or medical regimen. Following the hypocalcemic event, iPTH remained low even in those with severe hypocalcemia. The number of deaths and cardiovascular events did not differ between patients with and without hypocalcemia within six months following cinacalcet initiation.ConclusionTwo-thirds of cinacalcet initiated patients experienced hypocalcaemia with 9% being severe. Hypocalcemia was mostly asymptomatic, transient (with and without targeted intervention to correct it) and not associated with an increase in cardiovascular events or deaths.

Predictors of cinacalcet discontinuation and reinitiation in hemodialysis patients: results from 7 European countries

BackgroundThe putative benefits of cinacalcet therapy for management of secondary hyperparathyroidism (SHPT) are thought to be most manifested when patients are taking it consistently and as prescribed. Real-world descriptions of cinacalcet prescription discontinuation and reinitiation in European hemodialysis patients are lacking. To address this knowledge gap, we used Dialysis Outcomes and Practice Patterns Study (DOPPS) data, based on dialysis facility medical records, from seven European countries to estimate rates and predictors of cinacalcet prescription discontinuation and reinitiation in hemodialysis patients and to describe the trajectories of CKD-MBD laboratory values after discontinuation.MethodsCox regression analyses were used to predict (1) cinacalcet discontinuation among 613 patients with ≥3 consecutive months without cinacalcet prescription immediately prior to a new cinacalcet prescription and (2) cinacalcet reinitiation among 415 patients with a newly discontinued cinacalcet prescription immediately after ≥3 consecutive months of prescribed use.ResultsCinacalcet was discontinued in 21 and 35% of new users after 6 and 12 months, respectively. Cinacalcet was reinitiated in 38 and 49% of newly-discontinued users after 6 and 12 months, respectively. Predictors of discontinuation included lower parathyroid hormone (PTH) in the previous month (< 150 pg/ml vs. 150–299, HR = 2.57 [95% CI: 1.52–4.33]) and lower serum calcium in the previous month (< 8.4 mg/dl vs. 8.4–10.19, HR = 1.67 [95% CI: 1.08–2.59]). Predictors of reinitiation included higher PTH in the previous month (300–599 pg/ml vs. 150–299, HR = 1.88 [95% CI = 1.19–2.97]; 600+ pg/ml, HR = 3.02 [95% CI = 1.92–4.76]). After cinacalcet discontinuation, mean serum PTH increased from 408 to 510 pg/ml, mean serum calcium briefly rose from 9.12 to 9.22 mg/dl before declining to 9.06 mg/dl, and mean serum phosphorus showed little change.ConclusionsNephrologist discontinuation of cinacalcet therapy is common in European countries. Additional research is needed to identify optimal cinacalcet treatment strategies for SHPT management, including comparisons of intermittent cinacalcet therapy versus sustained treatment with reduced dose or frequency.

Guideline attainment and morbidity/mortality rates in a large cohort of European haemodialysis patients (EURODOPPS).

Haemodialysis patients experience a wide variety of intermediate complications, such as anaemia, hypertension and mineral bone disease (MBD). We aimed to assess the risk of death and hospital admissions as a function of the simultaneous attainment of different guideline targets (for hypertension, anaemia and MBD) in a large European cohort of dialysis patients. EURODOPPS is part of the Dialysis Outcomes and Practice Patterns Study (DOPPS) international, prospective cohort study of adult, in-centre haemodialysis patients for whom clinical data are extracted from medical records. In the present analysis, 6317 patients from seven European countries were included between 2009 and 2011. The percentages of patients treated according to the international guidelines on anaemia, hypertension and MBD were determined. The overall degree of guideline attainment was considered to be high if four or all five of the evaluated targets were attained, moderate if two or three targets were attained, and low if fewer than two targets were attained. Fully adjusted multivariate Cox models were used to investigate the relationship of target attainment with mortality and first hospital admission. At baseline, the degree of target attainment was low in 1751 patients (28%), moderate in 3803 (60%) and high in 763 (12%). In the fully adjusted model using time-dependent covariates, low attainment was associated with higher all-cause mortality [hazard ratio (95% confidence interval) = 1.19 (1.05-1.34)] and high attainment was associated with lower all-cause mortality [0.82 (0.68-0.99)]. In a similar model that additionally accounted for death as a competing risk, low and high attainments were not associated with hospital admission. In a large international cohort of dialysis patients, we have shown that more stringent application of guidelines is associated with lower mortality.

Risk of hospitalization associated with body mass index and weight changes among prevalent haemodialysis patients

The impact of body mass index (BMI) and body weight on hospitalization rates in haemodialysis patients is unknown.This study hypothesizes that being either underweight or obese is associated with a higher hospitalization rate.Observational study of 6296 European haemodialysis patients with prospective data collection and follow-up every six months for three years (COSMOS study). The risk of being hospitalized was estimated by a time-dependent Cox regression model and the annual risk (incidence rate ratios, IRR) by Poisson regression. We considered weight loss, weight gain and stable weight. Weight change analyses were also performed after patient stratification according to their baseline BMI.A total of 3096 patients were hospitalized at least once with 9731 hospitalizations in total. The hospitalization incidence (fully adjusted IRR 1.28, 95% CI [1.18–1.39]) was higher among underweight patients (BMI <20kg/m2) than patients of normal weight (BMI 20–25kg/m2), while the incidence of overweight (0.88 [0.83–0.93]) and obese patients (≥30kg/m2, 0.85 [0.79–0.92]) was lower. Weight gain was associated with a reduced risk of hospitalization. Conversely, weight loss was associated with a higher hospitalization rate, particularly in underweight patients (IRR 2.85 [2.33–3.47]).Underweight haemodialysis patients were at increased risk of hospitalization, while overweight and obese patients were less likely to be hospitalized. Short-term weight loss in underweight individuals was associated with a strikingly high hospitalization rate.

A model of vascular refilling with inflammation

Inflammation is prevalent in hemodialysis patients and is believed to significantly contribute to cardiovascular disease progression in end stage renal disease patients undergoing hemodialysis. Increased vascular permeability associated with inflammation is likely to influence the capillary wall properties, affecting vascular refilling during hemodialysis. In this paper, we present a model that incorporates inflammation into a vascular refilling model. We investigate how inflammation may affect the fluid volume and protein concentration dynamics in the plasma and interstitial spaces. In our work, we quantify inflammation by considering the concentration of the inflammatory biomarker C-reactive protein (CRP). Traditional sensitivity functions and subset selection based on asymptotic standard errors were used to aid in parameter identification. Estimates of the parameters were calculated from numerically generated measurements for fluid flux and hematocrit. Observations on the capillary wall properties, filtration and reflection coefficients, were done using data on mean CRP and serum albumin from a large population of European hemodialysis patients in their terminal two years before death and patients surviving for at least four years after dialysis initiation.

Risk of hospitalization associated with body mass index and weight changes among prevalent haemodialysis patients

The impact of body mass index (BMI) and body weight on hospitalization rates in haemodialysis patients is unknown.This study hypothesizes that being either underweight or obese is associated with a higher hospitalization rate.Observational study of 6296 European haemodialysis patients with prospective data collection and follow-up every six months for three years (COSMOS study). The risk of being hospitalized was estimated by a time-dependent Cox regression model and the annual risk (incidence rate ratios, IRR) by Poisson regression. We considered weight loss, weight gain and stable weight. Weight change analyses were also performed after patient stratification according to their baseline BMI.A total of 3096 patients were hospitalized at least once with 9731 hospitalizations in total. The hospitalization incidence (fully adjusted IRR 1.28, 95% CI [1.18–1.39]) was higher among underweight patients (BMI <20kg/m2) than patients of normal weight (BMI 20–25kg/m2), while the incidence of overweight (0.88 [0.83–0.93]) and obese patients (≥30kg/m2, 0.85 [0.79–0.92]) was lower. Weight gain was associated with a reduced risk of hospitalization. Conversely, weight loss was associated with a higher hospitalization rate, particularly in underweight patients (IRR 2.85 [2.33–3.47]).Underweight haemodialysis patients were at increased risk of hospitalization, while overweight and obese patients were less likely to be hospitalized. Short-term weight loss in underweight individuals was associated with a strikingly high hospitalization rate.

Acetate-free, citrate-acidified bicarbonate dialysis improves serum calcification propensity-a preliminary study.

A novel in vitro test (T50 test) assesses ex vivo serum calcification propensity and predicts mortality in chronic kidney disease and haemodialysis (HD) patients. For the latter, a time-dependent decline of T50 was shown to relate to mortality. Here we assessed whether a 3-month switch to acetate-free, citrate-acidified, standard bicarbonate HD (CiaHD) sustainably improves calcification propensity. T50 values were assessed in paired midweek pre-dialysis sera collected before and 3 months after CiaHD in 78 prevalent European HD patients. In all, 44 were then switched back to acetate. Partial correlation was used to study associations of changing T50 and changing covariates. Linear mixed effect models were built to assess the association of CiaHD and covariates with changing T50. A significant intra-individual increase of serum calcification resilience was found after 3 months on CiaHD (206 ± 56 to 242 ± 56 min; P < 0.001), but not after switching back to acetate (252 ± 63 to 243 ± 64 min; n = 44; P = 0.29). CiaHD, Δ serum phosphate and Δ albumin but not Δ ionized calcium and magnesium were the strongest determinants of changing T50. Beneath T50, only serum albumin but not phosphate changed significantly during 3 months of CiaHD. CiaHD dialysis favourably affected calcification propensity as measured by the T50 test. Whether this treatment, beyond established phosphate-directed treatments, has the potential to sustainably tip the balance towards a more anti-calcific serum milieu needs to be further investigated.

Geographical Variations in Blood Pressure Level and Seasonality in Hemodialysis Patients.

Seasons and climate influence the regulation of blood pressure (BP) in the general population and in hemodialysis patients. It is unknown whether this phenomenon varies across the world. Our objective was to estimate BP seasonality in hemodialysis patients from different geographical locations. Patients from 7 European countries (Spain, Italy, France, Belgium, Germany, United Kingdom, and Sweden) participating in the DOPPS (Dialysis Outcomes and Practice Patterns Study) on years 2005 to 2011 were studied. Factors influencing pre- and postdialysis systolic BP and diastolic BP levels were analyzed by mixed models. There were 9655 patients (median age, 68; 59% male) from 263 facilities, seen every 4 months during a median duration of 1.3 years. Pre- and postdialysis systolic BP increased by a mean estimate of 5.1 mm Hg (95% confidence interval [CI], 3.7-6.4 mm Hg) and 4.4 mm Hg (95% CI, 2.9-5.9 mm Hg) for each 10° increase in latitude (1111 km to the North). In the longitudinal analysis, predialysis systolic BP was lower in summer and higher in winter (difference, 1.7 mm Hg; 95% CI, 1.3-2.2 mm Hg), with greater differences in southern locations (Pinteraction=0.04). Predialysis systolic BP was inversely associated with outdoor temperature (-0.8 mm Hg/7.2°C; 95% CI, -1.0 to -0.5 mm Hg/7.2°C), with steeper slopes in southern locations (Pinteraction=0.005). Results were similar for predialysis diastolic BP. In conclusion, there is a geographical and seasonal gradient of BP in European hemodialysis patients. There is a need to consider these effects when evaluating and treating BP in this population and potentially in others.

HFE gene mutations are not risk factors for iron overload in European hemodialysis patients

<i>HFE</i> gene mutations are not risk factors for iron overload in European hemodialysis patients

Anti-parathyroid treatment effectiveness and persistence in incident haemodialysis patients with secondary hyperparathyroidism

BackgroundAnti-parathyroid treatment initiation and discontinuation are important decisions in chronic haemodialysis (HD) patients, where pill burden is often excessive. The present study aimed to describe secondary hyperparathyroidism (sHPT) drug therapy changes in HD patients. MethodsRetrospective observational cohort study of incident European HD patients with sHPT who were prescribed calcitriol or alfacalcidol (alpha calcitriol), paricalcitol or cinacalcet. ResultsTreatment-naïve patients prescribed alpha calcitriol (N=2259), paricalcitol (N=1689) and cinacalcet (N=1245) were considered for analysis. Serum intact parathyroid hormone (iPTH) levels decreased post-initiation with all treatment modalities; serum calcium and phosphate levels increased in response to activated vitamin D derivatives but decreased with cinacalcet. Approximately one-third of alpha calcitriol and paricalcitol patients but less than one-quarter of cinacalcet patients discontinued treatment. Although the three groups had comparable serum iPTH control at the time of treatment discontinuation, they differed in terms of calcium and phosphate levels. Following discontinuation, the evolution of laboratory parameters differed by treatment modality: whilst iPTH increased for all three treatment groups, calcium and phosphate decreased in patients who were being treated with alpha calcitriol and paricalcitol at the time of discontinuation, and increased in those who had been treated with cinacalcet. ConclusionsIn conditions of daily clinical practice, attaining and maintaining recommended biochemical control of sHPT appears to be more frequently achievable with cinacalcet than with activated vitamin D compounds.

Anti-parathyroid treatment effectiveness and persistence in incident haemodialysis patients with secondary hyperparathyroidism

BackgroundAnti-parathyroid treatment initiation and discontinuation are important decisions in chronic haemodialysis (HD) patients, where pill burden is often excessive. The present study aimed to describe secondary hyperparathyroidism (sHPT) drug therapy changes in HD patients. MethodsRetrospective observational cohort study of incident European HD patients with sHPT who were prescribed calcitriol or alfacalcidol (alpha calcitriol), paricalcitol or cinacalcet. ResultsTreatment-naïve patients prescribed alpha calcitriol (N=2259), paricalcitol (N=1689) and cinacalcet (N=1245) were considered for analysis. Serum intact parathyroid hormone (iPTH) levels decreased post-initiation with all treatment modalities; serum calcium and phosphate levels increased in response to activated vitamin D derivatives but decreased with cinacalcet. Approximately one-third of alpha calcitriol and paricalcitol patients but less than one-quarter of cinacalcet patients discontinued treatment. Although the three groups had comparable serum iPTH control at the time of treatment discontinuation, they differed in terms of calcium and phosphate levels. Following discontinuation, the evolution of laboratory parameters differed by treatment modality: whilst iPTH increased for all three treatment groups, calcium and phosphate decreased in patients who were being treated with alpha calcitriol and paricalcitol at the time of discontinuation, and increased in those who had been treated with cinacalcet. ConclusionsIn conditions of daily clinical practice, attaining and maintaining recommended biochemical control of sHPT appears to be more frequently achievable with cinacalcet than with activated vitamin D compounds.

Serum Magnesium and Sudden Death in European Hemodialysis Patients.

Despite suggestions that higher serum magnesium (Mg) levels are associated with improved outcome, the association with mortality in European hemodialysis (HD) patients has only scarcely been investigated. Furthermore, data on the association between serum Mg and sudden death in this patient group is limited. Therefore, we evaluated Mg in a post-hoc analysis using pooled data from the CONvective TRAnsport STudy (CONTRAST, NCT00205556), a randomized controlled trial (RCT) evaluating the survival risk in dialysis patients on hemodiafiltration (HDF) compared to HD with a mean follow-up of 3.1 years. Serum Mg was measured at baseline and 6, 12, 24 and 36 months thereafter. Cox proportional hazards models, adjusted for confounders using inverse probability weighting, were used to estimate hazard ratios (HRs) of baseline serum Mg on all-cause mortality, cardiovascular mortality, non-cardiovascular mortality and sudden death. A generalized linear mixed model was used to investigate Mg levels over time. Out of 714 randomized patients, a representative subset of 365 (51%) were analyzed in the present study. For every increase in baseline serum Mg of 0.1 mmol/L, the HR for all-cause mortality was 0.85 (95% CI 0.77–94), the HR for cardiovascular mortality 0.73 (95% CI 0.62–0.85) and for sudden death 0.76 (95% CI 0.62–0.93). These findings did not alter after extensive correction for potential confounders, including treatment modality. Importantly, no interaction was found between serum phosphate and serum Mg. Baseline serum Mg was not related to non-cardiovascular mortality. Mg decreased slightly but statistically significant over time (Δ -0.011 mmol/L/year, 95% CI -0.017 to -0.009, p = 0.03). In short, serum Mg has a strong, independent association with all-cause mortality, cardiovascular mortality and sudden death in European HD patients. Serum Mg levels decrease slightly over time.

Preservation of anemia control and weekly ESA dosage after conversion from PEG-Epoetin beta to darbepoetin alfa in adult hemodialysis patients: the TRANSFORM study.

IntroductionThere is scant real-world information on switching treatment for anemia associated with chronic kidney disease (CKD) from methoxy polyethylene glycol-epoetin beta (PEG-Epo) to darbepoetin alfa (DA). TRANSFORM was a multi-center, observational study designed to describe the time course of hemoglobin (Hb) concentration (primary outcome measure) and other parameters of clinical management of anemia in European hemodialysis patients in clinical practice before and after a switch from PEG-Epo to DA.MethodsEligible subjects were adult patients with CKD dialyzed at European dialysis centers for ≥26 weeks and treated with PEG-Epo for ≥14 weeks immediately prior to being switched to DA and no earlier than January 2011. Erythropoiesis-stimulating agent doses and Hb values were recorded for the 14-week pre-switch and 26-week post-switch periods.ResultsOf the 1,027 eligible patients enrolled at 42 hemodialysis centers in 7 European countries, 785 were included in analyses. Mean (95% confidence interval [CI]) Hb was generally stable: 11.19 (11.11, 11.26), 11.48 (11.40, 11.57), and 11.29 (11.20, 11.37) g/dL at month −1 pre-switch and months 3 and 6 post-switch, respectively. The geometric mean (95% CI) PEG-Epo dose at month −1 was 27.4 (26.0, 28.8) µg/week; DA dose was 29.4 (27.9, 30.9), 23.3 (21.9, 24.9), and 25.6 (24.1, 27.1) µg/week at months 1, 4, and 6, respectively. The geometric mean (95% CI) dose ratio at switching was 1.06 (1.01, 1.11). When stratifying by dose-ratio categories <0.8, 0.8–1.2, and >1.2 at switching, mean DA dose and Hb converged within narrow ranges by month 6 post-switch: 23.9–27.0 µg/week and 11.1–11.5 g/dL, respectively. Hb excursions <10 g/dL were less frequent post-switch versus pre-switch.ConclusionMean Hb values remained within a narrow range following switching from PEG-Epo to DA in this population of hemodialysis patients. Time trends of mean Hb and DA dose indicate that physicians titrated DA doses post-switch, to attain Hb concentrations comparable to those attained pre-switch with PEG-Epo.FundingAmgen (Europe) GmbH, Zug, Switzerland.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-014-0161-5) contains supplementary material, which is available to authorized users.