Resistance to erythropoiesis stimulating agents in patients treated with online hemodiafiltration and ultrapure low-flux hemodialysis: Results from a randomized controlled trial (CONTRAST)

Resistance to erythropoiesis stimulating agents (ESA) is common in patients undergoing chronic hemodialysis (HD) treatment. ESA responsiveness might be improved by enhanced clearance of uremic toxins of middle molecular weight, as can be obtained by hemodiafiltration (HDF). In this analysis of the randomized controlled CONvective TRAnsport STudy (CONTRAST; NCT00205556), the effect of online HDF on ESA resistance and iron parameters was studied. This was a prespecified secondary endpoint of the main trial. A 12 months' analysis of 714 patients randomized to either treatment with online post-dilution HDF or continuation of low-flux HD was performed. Both groups were treated with ultrapure dialysis fluids. ESA resistance, measured every three months, was expressed as the ESA index (weight adjusted weekly ESA dose in daily defined doses [DDD]/hematocrit). The mean ESA index during 12 months was not different between patients treated with HDF or HD (mean difference HDF versus HD over time 0.029 DDD/kg/Hct/week [20.024 to 0.081]; P = 0.29). Mean transferrin saturation ratio and ferritin levels during the study tended to be lower in patients treated with HDF (22.52% [24.72 to 20.31]; P = 0.02 and 249 ng/mL [2103 to 4]; P = 0.06 respectively), although there was a trend for those patients to receive slightly more iron supplementation (7.1 mg/week [20.4 to 14.5]; P = 0.06). In conclusion, compared to low-flux HD with ultrapure dialysis fluid, treatment with online HDF did not result in a decrease in ESA resistance

The cost-utility of haemodiafiltration versus haemodialysis in the Convective Transport Study

Background. Despite the growing interest in haemodiafiltration (HDF), there is no information on the costs and cost-utility of this dialysis modality yet. It was therefore our objective to study the cost-utility of HDF versus haemodialysis (HD). Methods. A cost-utility analysis was performed using a Markov model. It included data from the Convective Transport Study (CONTRAST), a randomized controlled trial that compared online HDF with low-flux HD. Costs were estimated using a societal perspective. Probabilistic sensitivity analyses were performed to study uncertainty. Results. Total annual costs for HDF and HD were (sic)88 622 +/- 19 272 and (sic)86 086 +/- 15 945, respectively (in 2009 euros). When modelled over a 5-year period, the incremental cost per quality-adjusted life year (QALY) of HDF versus HD was (sic)287 679. Sensitivity analyses revealed that this amount will not fall below (sic)140 000, even under the most favourable assumptions like a high-convection volume (>20.3 L). Conclusions. Based on accepted societal willingness-to-pay thresholds, HDF cannot be considered a cost-effective treatment for patients with end-stage renal disease at present. Apparently, minor additional costs of HDF are not counterbalanced by a relevant QALY gain

Hepcidin-25 in Chronic Hemodialysis Patients Is Related to Residual Kidney Function and Not to Treatment with Erythropoiesis Stimulating Agents

Hepcidin-25, the bioactive form of hepcidin, is a key regulator of iron homeostasis as it induces internalization and degradation of ferroportin, a cellular iron exporter on enterocytes, macrophages and hepatocytes. Hepcidin levels are increased in chronic hemodialysis (HD) patients, but as of yet, limited information on factors associated with hepcidin-25 in these patients is available. In the current cross-sectional study, potential patient-, laboratory- and treatment-related determinants of serum hepcidin-20 and -25, were assessed in a large cohort of stable, prevalent HD patients. Baseline data from 405 patients (62% male; age 63.7±13.9 [mean SD]) enrolled in the CONvective TRAnsport STudy (CONTRAST; NCT00205556) were studied. Predialysis hepcidin concentrations were measured centrally with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Patient-, laboratory- and treatment related characteristics were entered in a backward multivariable linear regression model. Hepcidin-25 levels were independently and positively associated with ferritin (p<0.001), hsCRP (p<0.001) and the presence of diabetes (p = 0.02) and inversely with the estimated glomerular filtration rate (p = 0.01), absolute reticulocyte count (p = 0.02) and soluble transferrin receptor (p<0.001). Men had lower hepcidin-25 levels as compared to women (p = 0.03). Hepcidin-25 was not associated with the maintenance dose of erythropoiesis stimulating agents (ESA) or iron therapy. In conclusion, in the currently studied cohort of chronic HD patients, hepcidin-25 was a marker for iron stores and erythropoiesis and was associated with inflammation. Furthermore, hepcidin-25 levels were influenced by residual kidney function. Hepcidin-25 did not reflect ESA or iron dose in chronic stable HD patients on maintenance therapy. These results suggest that hepcidin is involved in the pathophysiological pathway of renal anemia and iron availability in these patients, but challenges its function as a clinical parameter for ESA resistance

Endobronchial Treatment for Bronchial Carcinoid: Patient Selection and Predictors of Outcome

BACKGROUND: Traditionally, surgical resection is the preferred treatment for typical carcinoids and atypical carcinoids located in the lungs. Recently however, several studies have shown excellent long-term outcome after endobronchial treatment of carcinoid tumors located in the central airways. This study investigates clinical and radiological features as predictors of successful endobronchial treatment in patients with a bronchial carcinoid tumor. OBJECTIVES: To identify clinical and radiological features predictive of successful endobronchial treatment in patients with bronchial carcinoid. METHODS: This analysis was performed in a cohort of patients with typical and atypical bronchial carcinoid referred for endobronchial treatment. Several patient characteristics, radiological features, and histological grade (typical or atypical carcinoid) were tested as predictors of successful endobronchial treatment. RESULTS: One hundred and twenty-five patients with a diagnosis of bronchial carcinoid underwent endobronchial treatment. On multivariate analysis, a tumor diameter <15 mm (odds ratio 0.09; 95% confidence interval 0.02-0.5; p = <0.01) and purely intraluminal growth on computer tomography (CT scan) (odds ratio, 9.1; 95% confidence interval 1.8-45.8; p = <0.01) were predictive of radical endobronchial treatment. The success rate for intraluminal tumors with a diameter <20 mm was 72%. CONCLUSIONS: Purely intraluminal disease and tumor diameter on CT scan seem to be independent predictors for successful endobronchial treatment in patients with bronchial carcinoid. Based on these data, patients with purely intraluminal carcinoid tumors with a diameter <20 mm on CT scan are good candidates for endobronchial treatment, regardless of histological grade. In contrast, all patients with a tumor diameter ≥20 mm should be directly referred for surgery

Online hemodiafiltration reduces systemic inflammation compared to low-flux hemodialysis

Online hemodiafiltration may diminish inflammatory activity through amelioration of the uremic milieu. However, impurities in water quality might provoke inflammatory responses. We therefore compared the long-term effect of low-flux hemodialysis to hemodiafiltration on the systemic inflammatory activity in a randomized controlled trial. High-sensitivity C-reactive protein and interleukin-6 were measured for up to 3 years in 405 patients of the CONvective TRAnsport STudy, and albumin was measured at baseline and every 3 months in 714 patients during the entire follow-up. Differences in the rate of change over time of C-reactive protein, interleukin-6, and albumin were compared between the two treatment arms. C-reactive protein and interleukin-6 concentrations increased in patients treated with hemodialysis, and remained stable in patients treated with hemodiafiltration. There was a statistically significant difference in rate of change between the groups after adjustments for baseline variables (C-reactive protein difference 20%/year and interleukin-6 difference 16%/year). The difference was more pronounced in anuric patients. Serum albumin decreased significantly in both treatment arms, with no difference between the groups. Thus, long-term hemodiafiltration with ultrapure dialysate seems to reduce inflammatory activity over time compared to hemodialysis, but does not affect the rate of change in albumi

Studies on the effect of HDF versus HD on ESA resistance.

a<p>Ultrapure dialysis fluid is defined as <0.1 colony forming units per ml and <0.03 endotoxin units per ml <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094434#pone.0094434-Ledebo1" target="_blank">[28]</a>.</p

Baseline characteristics of patients who died during follow-up, from cardiovascular death, infection or dialysis withdrawal and of patients who survived (on treatment analysis).

<p>n.a. = not applicable; CVD = cardiovascular disease; AMI = acute myocardial infarction; CHD = coronary heart disease; TIA = transient ischemic accident; PAD = peripheral artery disease; DM = diabetes mellitus; BMI = body mass index; RKF = residual kidney function; AV = arterio-venous; CVC = central venous catheter; CRP = C- reactive protein;</p><p>IL-6 = interleukin-6; PCS = physical composite score; MCS = mental composite score; RAAS = renin angiotensin aldosterone system.</p><p>∧significantly different as compared to survivors, after adjustment for age and sex.</p>#<p>significantly different as compared to deaths due to dialysis withdrawal, after adjustment for age and sex.</p>¶<p>significantly different as compared to deaths due to infection, after adjustment for age and sex.</p>*<p>total vintage at time of end of study or date of drop-out for survivors.</p

CONSORT flow chart of patient inclusion.

<p>CONSORT flow chart of patient inclusion.</p

The distribution of death causes across age groups at time of death.

<p>The distribution of death causes across age groups at time of death.</p