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.

Fig 1. Flow chart of the study.

22 eligible chronic HD patients were recruited from two centers. Patients were treated with at least 3 months on high-flux HD and then switched to post-dilution online-HDF for 3 months. Dialysis prescription (time, blood flow rate, dialysate flow rate, dialyser type and size) and vascular access type were kept constant during each period.

Fig 2. Comparison of biomarkers in children on high-flux HD and HDF.

(A) Markers of oxidative stress (ox-LDL, AGEs) were significantly reduced in addition to improvement in total antioxidant capacity, however nitrosative stress (nitrotyrosine) was not changed on HDF compared to HD. (B) Markers of inflammation (ß2M, hsCRP) except IL-6 were reduced significantly while anti-inflammatory marker IL-10 was not changed on HDF compared to HD. (C) Markers of endothelial dysfunction (ADMA, SDMA) were reduced significantly on HDF compared to HD.

Fig 3

Percent increase in TAC and percent decrease in SDMA from HD to HDF was more pronounced in patients with higher blood flow rate (A,B). Higher blood flow rate was also associated with lower IL-6 to IL-10 ratio on HDF (C). Percent change = [(HDF-HD)/HD]*100.

Fig 4. Comparison of biomarkers in children with and without residual renal function (RRF) on high-flux HD and HDF.

Markers of oxidative stress (A), inflammation (B) and endothelial dysfunction (C) were significantly decreased in addition to a significant increase in anti-oxidant capacity on HDF compared to HD. This improvement was observed not only in patients without RRF but also in patients with RRF.

Fig 5. Demonstrating the molecular weights of the studied markers and comparison with albumin.

AGEs are not shown in the figure because they are composed of several molecules, which are mostly middle molecules.