Renal replacement therapy and bone mineral metabolism

Mineral bone disturbances are common in chronic kidney disease (CKD), and associated with significant risk of mortality and morbidity in patients on renal replacement therapy (RRT). Surrogate biomarkers of bone turnover such as parathyroid hormone (PTH), phosphate, calcium and Vitamin D are used to diagnose, evaluate, and guide treatment. This thesis examines the effect of RRT on mineral bone disturbances, it’s association with bone morbidity, and management strategies for phosphate control. Initially the incidence of radiologically proven bone fracture by site, in prevalent RRT groups is quantified and the relationship to associated risk factors studied. In this multicentre observational study of 2096 patients over a 3-year period the risk of fracture is higher in haemodialysis (HD) patients than in transplant patients even when controlling for other risk factors. Exposure to lanthanum and Vitamin D is apparently a protective factor in the HD group. I then examine a thrice-weekly nocturnal in-centre dialysis model in which we attain normal phosphate levels without dietary restriction or supplementation by altering the dialysis prescription and time. This observational trial over a 2-year period with over 2000 sessions of dialysis in 14 patients is associated with reduction of blood pressure medications. Subsequently I investigate the relationship of phosphate to FGF23 in a group of peritoneal dialysis patients. Finally, I study the effect of dialysis on clearances of FGF23 and expand on the knowledge of FGF-23 during a session of dialysis