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Hemodiafiltration is associated with reduced inflammation, oxidative stress and improved endothelial risk profile compared to high-flux hemodialysis in children.

ABSTRACT: Randomized trials in adults have shown reduced all-cause and cardiovascular mortality on hemodiafiltration (HDF) compared to high-flux hemodialysis (HD), but the mechanisms leading to improved outcomes are not clear. We studied biomarkers of inflammation, oxidative stress, anti-oxidant capacity and endothelial dysfunction in 22 children (13 female, age 8-15 years). All children received HD for at least 3 months, and were then switched to HDF, keeping all dialysis related parameters and dialysis time constant. All the biomarkers of inflammation (ß2-microglobulin, IL-6, IL-10, high sensitive C-reactive protein [hsCRP]), oxidative stress (nitrotyrosine, advanced glycation end-products [AGEs], oxidized low density lipoprotein [ox-LDL] and anti-oxidant capacity) and endothelial dysfunction (asymmetric dimethyl arginine [ADMA], symmetric dimethyl arginine [SDMA]), were comparable between incident and prevalent patients on HD, suggesting that even a short dialysis vintage of 3 months on HD increases inflammation and endothelial stress. After 3 months of HDF therapy there was a significant reduction in ß2-microglobulin (p<0.001), hCRP, ADMA, SDMA, AGEs, ox-LDL (p<0.01 for all) and an increase in total antioxidant capacity (p<0.001) compared to HD. All children were maintained on the same dialyser, dialysis water quality, dialysis time and blood flow speeds suggesting that improved clearances on HDF led to an improved biomarker profile. Even in children with residual renal function there was a significant reduction in ß2 microglobulin, hsCRP, SDMA, ox-LDL and AGEs on HDF compared to HD. Children with a lower blood flow had higher inflammatory status (higher IL-6/IL-10 ratio; p = 0.04, r = -0.43). Children who achieved a higher convective volume (?median 12.8L/m2) had lower ox-LDL (p = 0.02). In conclusion, we have shown that a significant improvement in inflammation, antioxidant capacity and endothelial risk profile is achieved even within a short time (3 months) on HDF compared to HD treatment. TRIAL REGISTRATION:ClinicalTrials.gov: NCT02063776.

SUBMITTER: Agbas A

PROVIDER: S-EPMC6005477 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Hemodiafiltration is associated with reduced inflammation, oxidative stress and improved endothelial risk profile compared to high-flux hemodialysis in children.

Ağbaş Ayşe A Canpolat Nur N Çalışkan Salim S Yılmaz Alev A Ekmekçi Hakan H Mayes Mark M Aitkenhead Helen H Schaefer Franz F Sever Lale L Shroff Rukshana R

PloS one 20180618 6

Randomized trials in adults have shown reduced all-cause and cardiovascular mortality on hemodiafiltration (HDF) compared to high-flux hemodialysis (HD), but the mechanisms leading to improved outcomes are not clear. We studied biomarkers of inflammation, oxidative stress, anti-oxidant capacity and endothelial dysfunction in 22 children (13 female, age 8-15 years). All children received HD for at least 3 months, and were then switched to HDF, keeping all dialysis related parameters and dialysis ...[more]

PMID: 29912924

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Project description:BackgroundPatients on dialysis have a high burden of bone-related comorbidities, including fractures. We report a post hoc analysis of the prospective cohort study HDF, Hearts and Heights (3H) to determine the prevalence and risk factors for chronic kidney disease-related bone disease in children on hemodiafiltration (HDF) and conventional hemodialysis (HD).MethodsThe baseline cross-sectional analysis included 144 children, of which 103 (61 HD, 42 HDF) completed 12-month follow-up. Circulating biomarkers of bone formation and resorption, inflammatory markers, fibroblast growth factor-23, and klotho were measured.ResultsInflammatory markers interleukin-6, tumor necrosis factor-α, and high-sensitivity C-reactive protein were lower in HDF than in HD cohorts at baseline and at 12 months (P < .001). Concentrations of bone formation (bone-specific alkaline phosphatase) and resorption (tartrate-resistant acid phosphatase 5b) markers were comparable between cohorts at baseline, but after 12-months the bone-specific alkaline phosphatase/tartrate-resistant acid phosphatase 5b ratio increased in HDF (P = .004) and was unchanged in HD (P = .44). On adjusted analysis, the bone-specific alkaline phosphatase/tartrate-resistant acid phosphatase 5b ratio was 2.66-fold lower (95% confidence interval, -3.91 to -1.41; P < .0001) in HD compared with HDF. Fibroblast growth factor-23 was comparable between groups at baseline (P = .52) but increased in HD (P < .0001) and remained unchanged in HDF (P = .34) at 12 months. Klotho levels were similar between groups and unchanged during follow-up. The fibroblast growth factor-23/klotho ratio was 3.86-fold higher (95% confidence interval, 2.15-6.93; P < .0001) after 12 months of HD compared with HDF.ConclusionChildren on HDF have an attenuated inflammatory profile, increased bone formation, and lower fibroblast growth factor-23/klotho ratios compared with those on HD. Long-term studies are required to determine the effects of an improved bone biomarker profile on fracture risk and cardiovascular health.

Project description:This prospective multicenter randomized comparative cross-over trial aimed at evaluating the influence of hemodialysis vs post-dilution hemodiafiltration with high-flux dialyzers in solute clearance and biocompatibility profile. 32 patients were sequentially dialyzed with Leoceed-21HX, Polypure-22S+, Rexsys-27H and VIE-21A. Primary outcome was β2-microglobulin removal. Secondary outcomes were (i) extraction of other uremic solutes (ii) parameters of inflammation and nutrition and (iii) comparative quantification of perdialytic albumin losses (using total 'TDC' vs partial 'PDC' collection of dialysate). Significant increases in removal rates of β2-microglobulin (84.7 ± 0.8 vs 71.6 ± 0.8 mg/L), myoglobin (65.9 ± 1.3 vs 38.6 ± 1.3 µg/L), free immunoglobulin light chains Kappa (74.9 ± 0.8 vs 55.6 ± 0.8 mg/L), β-trace protein (54.8 ± 1.3 vs 26.8 ± 1.4 mg/L) and orosomucoid (11.0 ± 1.1 vs 6.0 ± 1.1 g/L) but not myostatin (14.8 ± 1.5 vs 13.0 ± 1.5 ng/mL) were observed in HDF compared to HD when pooling all dialyzers. Rexsys and VIE-A use in both HD and HDF subgroups was associated to a better removal of middle/large-size molecules compared to Leoceed and Polypure, except β2-microglobulin for Rexsys. Inflammatory parameters were unchanged between dialyzers without any interaction with dialysis modality. Mean dialysate albumin loss was comparable between TDC and PDC (1.855 vs 1.826 g/session for TDC and PDC respectively). In addition, a significant difference in albumin loss was observed between dialyzers with the highest value (4.5 g/session) observed using Rexsys. Use of all dialyzers was associated with good removals of the large spectrum of uremic toxins tested and good biocompatibility profiles, with an additional gain in removal performances with HDF. Larger surface area, thinner wall and resultant very high ultrafiltration coefficient of Rexsys should be taken into account in its clear performance advantages.

Dataset Information

Hemodiafiltration is associated with reduced inflammation, oxidative stress and improved endothelial risk profile compared to high-flux hemodialysis in children.

Publications

Hemodiafiltration is associated with reduced inflammation, oxidative stress and improved endothelial risk profile compared to high-flux hemodialysis in children.

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