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.

Effects of online hemodiafiltration on anemia and nutritional status in chronic hemodialysis patients

“…According to a US Renal Data System report, 87.3% of incident patients with ESRD in the US used HD for RRT in 2016. The recent introduction of online-hemodiafiltration (OL-HDF) may offer major advantages in clearing molecules of various sizes, reducing HD-associated amyloidosis and chronic inflammation [5][6][7]. Because this modality has been officially approved for ESRD patients, the number of patients worldwide undergoing OL-HDF therapy doubled between 2004 and 2010, reaching 80,000 [8].…”

Effects of Hemodiafiltration versus Conventional Hemodialysis in Children with ESKD: The HDF, Heart and Height Study

“…11 Even within a short period of 3 months on conventional hemodialysis (HD), biomarkers of inflammation, oxidative stress, and endothelial dysfunction were shown to increase. 12 Clearly, the sine qua non is prevention, but no studies in children have shown how to prevent the inexorable progression of CVD in patients on dialysis.…”

Variations in Circulating Active MMP-9 Levels during Renal Replacement Therapy

“…In the case of ESRD, and especially dialysis, there are conflicting results on the levels of MMP-9 in the pre-and post-dialysis states [32,33]. This could be due to the different types of dialysis membranes [34,35], or to the type of dialysis itself [19,25]. We demonstrate herein that active MMP-9 is cleared during dialysis when the type of dialysis is not considered, but a decrease in active MMP-9 is only seen in HFD.…”

“…In addition, the type of dialysis used directly influences the oxidative status of the patients. Indeed, recent studies demonstrate that patients under OL-HDF have less inflammation, endothelial damage, and oxidative stress [19,24,25], which could be associated with the improved prognosis in this group [26,27]. The reduction in middle-molecules is associated with the preservation of residual renal function [28], which decreases the mortality risk in dialysis [29] and is improved in OL-HDF [30].…”