Models of Phosphate Kinetics in the Setting of Hemodialysis

High plasma phosphate concentration, hyperphosphatemia, is an electrolyte disturbance in patients with chronic kidney disease (CKD); 40% of 45% of patients with end-stage CKD experience it. The usual treatment to maintain phosphate concentrations in the normal range is dialysis. In general, maintaining a normal phosphate balance in patients on dialysis is desirable because it may help prevent severe complications such as vascular calcifications, renal osteodystrophy, and hyperparathyroidism.

Preventing hyperphosphatemia relies on an understanding of phosphate kinetics in dialysis patients. Physiologic modeling has been used to gain new insights into phosphate behavior, and various models to describe and quantify intra- and/or interdialytic phosphate kinetics have been suggested; however, there are few studies comparing the available models. Sisse H. Laursen, MSc, and colleagues in Demark conducted a systematic review and analysis of existing published models of phosphate metabolism in the setting of maintenance hemodialysis therapy. They reported results of the review in the American Journal of Kidney Diseases [2018; 71(1):75-90].

Eligibility criteria were studies of phosphate modeling within hemodialysis therapy published prior to August 31, 2016. The search was restricted to full-text peer-reviewed journal articles in English that focused on intradialytic or intra- and interdialytic phosphate kinetic modeling. Excluded studies focused only on dialytic phosphate removal, peritoneal dialysis, hemodiafiltration treatment, hemofiltration treatment, and/or urgent dialysis.

The researchers evaluated 1964 nonduplicate studies; of those, 11 were included in the analysis. The 11 studies comprised nine different phosphate models. The model approaches included 1-, 2-, 3-, and 4-compartment structures; the number of model parameters ranged from two to 11.

All 11 studies agreed that the observed mobilization of phosphate requires some kind of generation term. In addition, the intra- and extracellular compartments were set to be equal to the included compartments in the majority of the studies.

Using the Newcastle-Ottawa Scale with 14 quality indicators, the scores of the included studies ranged from two to 11. Two of the studies were ranked low quality, six were medium quality, and three were considered high quality. The studies ranked high quality were more likely to have been published recently; the exception was a study from 2012 with a score of four that was assessed as poor quality (the score is preliminary because the model has not yet been validated).

The three indicators that were most frequently met were: (1) transparency of the model approach; (2) presentation of the model parameters; and (3) conclusions. The indicators that were considered to be of a lower quality were: (1) treatment setup and (2) study design.

All of the studies were in agreement that a model should consist of a minimum of two compartments to ensure stabilization of phosphate. Four of the models suggest that it can be difficult to predict and describe phosphate rebound even using a 2-compartment structure. The studies also indicate that for kinetic phosphate models to succeed, they should have high accountability and accuracy.

Limitations to the analysis cited by the authors included reviewing studies that used varying treatment setups and sampling methods; focusing solely on phosphate modeling in the setting hemodialysis therapy without considering hemodiafiltration models; and reviewing only studies published in English.

“Many parameters known to influence phosphate balance are not included in existing phosphate models that do not fully reflect the physiology of phosphate metabolism in the setting of hemodialysis. Moreover, models have not been sufficiently validated for their use as a tool to simulate phosphate kinetics in hemodialysis therapy,” the authors said.

Takeaway Box

  1. Researchers in Denmark conducted a systematic review and analysis of studies describing models of phosphate metabolism in the setting of maintenance hemodialysis.
  2. Of 1964 nonduplicate studies evaluated, the review and analysis included 11, comprising nine different phosphate models with 1-, 2-. 3- or 4-compartment assumptions.
  3. The analysis found that parameters known to influence phosphate balance are not included in existing phosphate models that do not fully reflect the physiology of phosphate metabolism in the setting of hemodialysis.