SAT-040 HAEMODIAFILTRATION IMPROVES THE CARDIOVASCULAR RISK PROFILE AND PATIENT RELATED OUTCOME MEASURES COMPARED TO CONVENTIONAL HAEMODIALYSIS IN CHILDREN – THE HDF, HEART AND HEIGHT (3H) STUDY

Abstract

Fluid overload, hypertension and cardiovascular disease are common in children on dialysis. In adults, haemodiafiltration (HDF) is shown to reduce cardiovascular mortality compared to conventional haemodialysis (HD), but causes for this are not clear and data in children are scarce. We performed a non-randomized parallel-arm clinical trial within the International Paediatric Haemodialysis Network registry to compare outcomes on HD versus post-dilution on-line HDF: the HDF, Heart and Height (3H) study. Co-primary outcome measures were annualised changes in carotid intima-media thickness standard deviation score (cIMT-SDS) and height-SDS. ClinicalTrials.gov: NCT02063776 190 children (from 28 centres in 10 countries across Europe and North America) were recruited, and 177 fulfilled inclusion criteria. 133 children (78 on HD and 55 on HDF) completed one-year follow-up. There was no difference between HD and HDF groups in age, gender, underlying renal disease, comorbidities, dialysis vintage, access type, blood flow or presence of residual renal function. There were 44 dropouts, mainly (79%) due to transplantation; there were no deaths. The median convective volume achieved in the HDF group was 13.33 (inter-quartile range 12.4 to 14.5) ml/m2/session. Annualised change in cIMT SDS was 10-fold lower in HDF compared to HD (0.013 vs 0.48; p=0.002; Figure 1). On propensity score analysis, after adjusting for potential confounders, children on HD had a +0.47 greater increase in annualised cIMT-SDS (95%CI 0.07-0.87; p=0.02) compared to those on HDF. The 24-hour mean arterial pressure (MAP)-SDS increased on HD but reduced on HDF. Serum β2-microglobulin, PTH and high-sensitivity CRP were lower and haemoglobin was higher in HDF patients at 1-year. Predictors of higher cIMT-SDS and MAP-SDS at 12-months (data adjusted for country and baseline values) were HD group, higher inter-dialytic weight gain and ultrafiltration rate and higher β2-microglobulin. Height-SDS increased in HDF but remained static in HD. Importantly, the type of vascular access, blood flow rate and residual renal function did not correlate with cIMT SDS, suggesting that convective clearance is a significant determinant of outcome. Patient related outcome measures that are primarily associated with fluid status, such as the post-dialysis recovery time, headaches, dizziness and cramps, were less frequent and less severe in HDF compared to HD patients. Lower inter-dialytic weight gain on HDF, implying lower ultrafiltration rates per session and greater hemodynamic stability, was strongly associated with fewer symptoms. HDF patients had improved school attendance and greater physical activity scores, but there was no difference in hospitalisation rates. A significant limitation of the study is that randomization was not possible due to small patient numbers. In conclusion, 3H, the largest paediatric dialysis study to date, has shown that HDF improves blood pressure and hemodynamic stability and increases the removal of middle-molecular weight uremic toxins that may, in turn, may halt the progression of vascular disease, improve growth rates and patient related outcome measures compared to conventional HD. Randomised trials to study to confirm these outcomes are required.