Hemodiafiltration Reduces All-Cause and Cardiovascular Mortality in Incident Hemodialysis Patients: A Propensity-Matched Cohort Study.

BACKGROUND: The majority of studies suggesting that online hemodiafiltration reduces the risk of mortality compared to hemodialysis (HD) have been performed in dialysis-prevalent populations. In this report, we conducted an epidemiologic study of mortality in incident dialysis patients, comparing post-dilution online hemodiafiltration and high-flux HD, with propensity score matching (PSM) used to correct indication bias. METHODS: Our study cohort comprised 3,075 incident dialysis patients treated in 64 Spanish Fresenius Medical Care clinics between January 2009 and December 2012. The primary outcome of this study was to investigate the impact of the type of renal replacement on all-cause mortality. An analysis of cardiovascular mortality was defined as the secondary outcome. To achieve these objectives, patients were followed until December 2016. Patients were categorized as high-flux HD patients if they underwent this treatment exclusively. If >90% of their treatment was with online hemodiafiltration, then the patient was grouped to that modality. RESULTS: After PSM, a total of 1,012 patients were matched. Compared with patients on high-flux HD, those on online hemodiafiltration received a median replacement volume of 23.45 (interquartile range 21.27-25.51) L/session and manifested 24 and 33% reductions in all-cause and cardiovascular mortality (all-cause mortality hazards ratio [HR] 0.76, 95% CI 0.62-0.94 [p = 0.01]; and cardiovascular mortality HR 0.67, 95% CI 0.50-0.90 [p = 0.008]). CONCLUSIONS: This study shows that post-dilution online hemodiafiltration reduces all-cause and cardiovascular mortality compared to high-flux HD in an incident HD population.

The relationship of NT-proBNP and dialysis parameters with outcome of incident haemodialysis patients: results from the membrane permeability outcome study.

BACKGROUND/AIMS: The association of raised levels of natriuretic peptides with elevated risk of mortality was investigated in the present analysis of the Membrane Permeability Outcome study. METHODS: N-terminal probrain type natriuretic peptide (NT-proBNP) was measured in 618 incident haemodialysis patients, randomised to either high-flux or low-flux. Characteristics of patients with NT-proBNP levels below or above the median were descriptively analysed and survival analysis was performed. RESULTS: Median NT-proBNP value was 2,124 pg/ml, with 1,854 pg/ml in the high-flux and 2,919 pg/ml in the low-flux group. Survival probability was lowest in patients with both a history of cardiovascular disease and NT-proBNP values above the median (p < 0.001). A multivariate Cox proportional hazard model showed interaction between presence of cardiovascular diseases and NT-proBNP levels above the median. CONCLUSIONS: NT-proBNP is an independent predictor of mortality also in incident haemodialysis patients. Lower concentrations associated with high-flux dialysis suggest a possible biological link to improved survival in this group.

Correction of 25-OH-vitamin D deficiency improves control of secondary hyperparathyroidism and reduces the inflammation in stable haemodialysis patients. / La corrección del déficit de 25-OH-vitamina D mejora el control del hiperparatiroidismo secundario y el estado inflamatorio de pacientes estables en hemodiálisis.

INTRODUCTION: Patients on haemodialysis (HD) have a high prevalence of 25-OH-vitamin D (25-OH-D)deficiency. Secondary hyperparathyroidismis a common condition in these patients, which is very important to control. 25-OH-D is involved in regulating calcium homeostasis. As such, appropriate levels of this vitamin could help to control bone mineral metabolism. OBJECTIVE: To evaluate the effect 25-OH-D repletion in HD patients with 25-OH-D deficiency (<20ng/ml) on the control of secondary hyperparathyroidism and microinflammation status. PATIENTS AND METHODS: Prospective observational study in which stable patients on HD with 25-OH-D deficiency (<20ng/ml) were treated with oral calcifediol 0.266mcg/every 2 weeks for three months. Dialysis characteristics, biochemical parameters and drug doses administered were analysed before and after the correction of the deficiency. RESULTS: Forty-five stable HD patients with a mean age of 74.08±12.49 years completed treatment. Twenty-seven patients (60%) achieved 25-OH-D levels above 20ng/ml (23 with levels>30ng/ml and 4 between 20-30ng/ml). Parathyroid hormone levels decreased in 32 of the 45 patients, 23 of which (51%) achieved a>30% decrease from baseline. In terms of concomitant treatment, we observed a significant reduction in the selective vitamin D receptor activator dose, but no changes in calcimimetic or phosphate binders administration. In terms of malnutrition-inflammation status, a decrease in C-reactive protein was noted, although other microinflammation parameters, such as activated monocytes (CD14+/CD16+ and CD 14++/CD16+) were unchanged. No changes were observed in the levels of FGF-23. CONCLUSIONS: Correcting 25-OH-D deficiency in HD patients is associated with better secondary hyperparathyroidism control with lower doses of vitamin D analogues, as well as an improvement in inflammatory status. Our results support the recommendation to determine 25-OH-D levels and correct its deficiency in these patients.

Microinflammation in hemodialysis is related to a preactivated subset of monocytes.

Increased percentage of monocytes with low CD14 expression and that co-express CD16 (CD14+/CD16+) have been reported in hemodialysis (HD) patients. We sought to determine whether CD14+/CD16+ monocytes in HD therapy are sensibilized cells to a proinflammatory activity. Cells from 32 HD patients, and from 9 Systemic Lupus Erythematosus (SLE), 9 individuals with human immunodeficiency virus (HIV)-1- and 15 healthy controls were studied. Cells were analyzed by means of flow cytometry for CD14/CD16 expression and immune function (cytokine, chemokines, and sialoadhesin expression), and phagocytosis. Increased percentage of CD14+/CD16+ monocytes was observed in HD patients. Compared with CD14++ monocytes, the CD14+/CD16+ monocytes exhibited increased expression of proinflammatory cytokines and markers of differentiated cells. In addition, these monocytes showed an increased phagocytic activity. Similarly, CD14+/CD16+ monocytes from SLE and HIV patients showed increased inflammatory activity as compared with CD14++ cells. These results support that CD14+/CD16+ monocytes from HD patients evidence characteristics of primed prestimulated proinflammatory cells, similar to data observed in SLE and HIV.

La corrección del déficit de 25-OH-vitamina D mejora el control del hiperparatiroidismo secundario y el estado inflamatorio de pacientes estables en hemodiálisis / Correction of 25-OH-vitamin D deficiency improves control of secondary hyperparathyroidism and reduces the inflammation in stable haemodialysis patients

Introducción: El déficit de 25-OH-vitamina D (25-OH-D) es común en los pacientes en hemodiálisis (HD). Por otra parte, es bien conocida la elevada incidencia de hiperparatiroidismo secundario en este grupo de pacientes, y lo importante que es su adecuado control. La 25-OH-D está implicada en la regulación de la homeostasis del calcio, por lo que tener niveles adecuados puede contribuir en el control del metabolismo óseo-mineral. Objetivos: Evaluar el efecto de la repleción de 25-OH-D en pacientes en HD con déficit vitamínico (niveles<20ng/ml), en el control del hiperparatiroidismo secundario y en el estado de microinflamación. Pacientes y métodos: Estudio observacional, prospectivo en el que se trataron pacientes estables en HD con déficit de 25-OH-D (<20ng/ml), con calcifediol 0,266mcg/15 días vía oral durante 3 meses. Los datos de HD, parámetros bioquímicos y las dosis de fármacos administrados fueron analizados antes y después de la corrección del déficit. Resultados: Un total de 45 pacientes estables en HD con edad media 74,08±12,49 años completaron el tratamiento. Del total, 27 pacientes (60%) alcanzaron niveles de 25-OH-D>20ng/ml (en 23 fueron>30ng/ml, y 4 entre 20-30ng/ml). Las cifras de hormona paratiroidea descendieron en 32 de los 45 pacientes, alcanzando en 23 (51% de tratados) un descenso>30% respecto al valor basal. En cuanto al tratamiento concomitante, se objetivó un descenso significativo de la dosis de activador selectivo del receptor de vitamina D; sin evidenciarse cambios en la dosis de calcimimético ni de quelantes. Respecto al estado de malnutrición-inflamación, destaca un descenso de la proteína C reactiva, aunque no se modificaron otros parámetros de microinflamación como los monocitos activados (CD14+/CD16+ y CD 14++/CD16+). Tampoco se observaron cambios en los niveles de FGF-23. Conclusiones: La corrección del déficit de 25-OH-D en pacientes en HD se asocia a un mejor control del hiperparatiroidismo secundario con menores dosis de análogos de vitamina D y a una mejoría en el estado inflamatorio de estos pacientes. Nuestros resultados apoyan la recomendación de determinar niveles de 25-OH-D y corregir el déficit en pacientes en HD (AU)

Introduction: Patients on haemodialysis (HD) have a high prevalence of 25-OH-vitamin D (25-OH-D)deficiency. Secondary hyperparathyroidismis a common condition in these patients, which is very important to control. 25-OH-D is involved in regulating calcium homeostasis. As such, appropriate levels of this vitamin could help to control bone mineral metabolism. Objective: To evaluate the effect 25-OH-D repletion in HD patients with 25-OH-D deficiency (<20ng/ml) on the control of secondary hyperparathyroidism and microinflammation status. Patients and methods: Prospective observational study in which stable patients on HD with 25-OH-D deficiency (<20ng/ml) were treated with oral calcifediol 0.266mcg/every 2 weeks for three months. Dialysis characteristics, biochemical parameters and drug doses administered were analysed before and after the correction of the deficiency. Results: Forty-five stable HD patients with a mean age of 74.08±12.49 years completed treatment. Twenty-seven patients (60%) achieved 25-OH-D levels above 20ng/ml (23 with levels>30ng/ml and 4 between 20-30ng/ml). Parathyroid hormone levels decreased in 32 of the 45 patients, 23 of which (51%) achieved a>30% decrease from baseline. In terms of concomitant treatment, we observed a significant reduction in the selective vitamin D receptor activator dose, but no changes in calcimimetic or phosphate binders administration. In terms of malnutrition-inflammation status, a decrease in C-reactive protein was noted, although other microinflammation parameters, such as activated monocytes (CD14+/CD16+ and CD 14++/CD16+) were unchanged. No changes were observed in the levels of FGF-23. Conclusions: Correcting 25-OH-D deficiency in HD patients is associated with better secondary hyperparathyroidism control with lower doses of vitamin D analogues, as well as an improvement in inflammatory status. Our results support the recommendation to determine 25-OH-D levels and correct its deficiency in these patients (AU)

On-line hemodiafiltration reduces the proinflammatory CD14+CD16+ monocyte-derived dendritic cells: A prospective, crossover study.

It is not known whether high convective transport may have a role in modulating the chronic inflammation of hemodialysis (HD) patients. The aim of this study was to evaluate the effect of on-line hemodiafiltration (OL-HDF) on proinflammatory peripheral monocytes: Percentage of CD14+CD16+ cells and their telomere length and spontaneous or bacterial DNA-induced production of cytokines (TNF-alpha and IL-6). In a prospective, crossover study, 31 patients who were on high-flux HD (HF-HD) were evaluated. Patients underwent the following sequence of treatments (4 mo each): HF-HD (basal), OL-HDF (period 1), HF-HD (period 2), OL-HDF (period 3), and HF-HD (period 4). The dialysis characteristics were similar in the two modalities; the only difference was a higher convective transport in the OL-HDF than in the HF-HD. All patients who were on OL-HDF periods showed a significantly lower number of CD14+CD16+ cells than on HF-HD (18.5 +/- 2.3 basal versus 13.6 +/- 2.9 period 1 and 13.9 +/- 2.3 period 3; P = 0.001). By contrast, HF-HD restored the number of CD14+CD16+ cells to the basal values (19.2 +/- 2.8 and 18.6 +/- 1.4, periods 2 and 4, respectively; NS). During OL-HDF periods, the reduction of CD14+CD16+ was paralleled by a decreased number of short telomere cells. Spontaneous or bacterial DNA-induced production of cytokines (TNF-alpha and IL-6) was increased in HF-HD as compared with OL-HDF. In conclusion, these results demonstrate that as compared with HF-HD, OL-HDF markedly reduces the number of proinflammatory CD14+CD16+ cells and the production of TNF-alpha and IL-6. Future studies are needed to assess the possible therapeutic effect of convective transport on chronic inflammation that is associated with HD.