A randomized cross-over trial of pre-and post-filter hemodiafiltration modalities in children on maintenance dialysis -- effects on solute removal and blood pressure.

INTRODUCTION: Children on post-filter hemodiafiltration (post-HDF) have reduced cardiovascular damage and improved growth compared to conventional hemodialysis. High convection volumes in post-HDF are associated with improved outcomes. Even higher convection volumes can be reached with pre-filter HDF (pre-HDF). However, data is limited. Here, we compare the effect of pre- vs post-HDF on solute removal, inflammation, nutrition markers and blood pressure in a randomized, multicenter cross-over trial. METHODS: After a four-week wash-out period in post-HDF, 24 children on maintenance dialysis were randomized either to four-weeks pre- then four-weeks post-HDF, or vice-versa, keeping all other dialysis related parameters constant. The primary outcome measure was reduction in α1-microglobulin, a large-middle molecular weight (MW) uremic retention solute. RESULTS: Twenty-one patients completed the study. The median age was 15.1 years, with 15(71%) girls. Median convection volumes were 36.2 (inter quartile range 32;40) vs 14.3 (12.9;15.8) l/m2 body surface area per session in pre-HDF and post-HDF respectively. Pre-dialysis α1- microglobulin [median difference -17.0 ng/ml (95% confidence interval (CI) -27.0;-3.5)], ß2-microglobulin [-5.19 mg/l (95%CI -9.34;-1.76)] and myoglobin [-76.0 ng/ml (95%CI-100;-44.5)] concentrations were significantly lower, and reduction ratios (RR) were significantly higher in pre-HDF compared with post-HDF. Interleukin-10, tumor necrosis factor-α and high sensitivity C-reactive protein were significantly lower in pre-HDF. Pre-HDF achieved significantly higher RRs of total indoxyl sulfate and p-cresyl sulfate. The RR for small MW solutes, Kt/V and serum albumin did not differ meaningfully between modalities. Diastolic blood pressure was significantly higher in pre-HDF, correlating with higher replacement volume and higher post-dialysis serum sodium concentration. CONCLUSIONS: Pre-HDF achieves superior removal of middle and larger-middle MW uraemic retention solutes and was associated with a more favorable inflammatory profile, without compromising small MW retention solute removal or albumin levels, compared to post-HDF. Pre-HDF may be associated with higher blood pressure in a sub-set of patients, potentially due to greater sodium load from higher replacement volumes.