Hemodiafiltration Is Associated With Reduced Inflammation and Increased Bone Formation Compared With Conventional Hemodialysis in Children: The HDF, Hearts and Heights (3H) Study

Background: Patients 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). Methods: The 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. Results: Inflammatory 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. Conclusion: Children 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.