Effect of post-dilutional on-line haemodiafiltration on serum calcium, phosphate and parathyroid hormone concentrations in uraemic patients

Elevated bone mineral parameters have been associated with mortality in dialysis patients. There are conflicting data about calcium, parathyroid hormone (PTH), and mortality and few data about changes in bone mineral parameters over time. We conducted a prospective cohort study of 1007 incident hemodialysis and peritoneal dialysis patients. We examined longitudinal changes in bone mineral parameters and whether their associations with mortality were independent of time on dialysis, inflammation, and comorbidity. Serum calcium, phosphate, and calcium-phosphate product (CaP) increased in these patients between baseline and 6 months (P<0.001) and then remained stable. Serum PTH decreased over the first year (P<0.001). In Cox proportional hazards models adjusting for inflammation, comorbidity, and other confounders, the highest quartile of phosphate was associated with a hazard ratio (HR) of 1.57 (1.07-2.30) using both baseline and time-dependent values. The highest quartiles of calcium, CaP, and PTH were associated with mortality in time-dependent models but not in those using baseline values. The lowest quartile of PTH was associated with an HR of 0.65 (0.44-0.98) in the time-dependent model with 6-month lag analysis. We conclude that high levels of phosphate both at baseline and over follow-up are associated with mortality in incident dialysis patients. High levels of calcium, CaP, and PTH are associated with mortality immediately preceding an event. Promising new interventions need to be rigorously tested in clinical trials for their ability to achieve normalization of bone mineral parameters and reduce deaths of dialysis patients.

Hyperphosphatemia in the hemodialysis population is ubiquitous, but phosphate kinetics during hemodialysis is poorly understood. Twenty-nine hemodialysis patients each received one long and one short dialysis, equivalent in terms of urea clearance. Phosphate concentrations were measured during each treatment and for one hour thereafter. A new model of phosphate kinetics was developed and implemented in VisSim. This model characterized additional processes involved in phosphate kinetics explaining the departure of the measured data from a standard two-pool model. Pre-dialysis phosphate concentrations were similar in long and short dialysis groups. Post-dialysis phosphate concentrations in long dialysis were higher than in short dialysis (P < 0.02) despite removal of a greater mass of phosphate (P < 0.001). In both long and short dialysis serum phosphate concentrations initially fell in accordance with two-pool kinetics, but thereafter plateaued or increased despite continuing phosphate removal. Implementation of an additional regulatory mechanism such that a third pool liberates phosphate to maintain an intrinsic target concentration (1.18 +/- 0.06 mmol/L; 95% confidence intervals, CI) explained the data in 24% of treatments. The further addition of a fourth pool hysteresis element triggered by critically low phosphate levels (0.80 +/- 0.07 mmol/L, CI) yielded an excellent correlation with the observed data in the remaining 76% of treatments (cumulative standard deviation 0.027 +/- 0.004 mmol/L, CI). The critically low concentration correlated with pre-dialysis phosphate levels (r=0.67, P < 0.0001). Modeling of phosphate kinetics during hemodialysis implies regulation involving up to four phosphate pools. The accuracy of this model suggests that the proposed mechanisms have physiological validity.