Elimination of Phosphate in HD and PD Reference: Kuhlmann MK. Phosphate elimination in modalities of hemodialysis and peritoneal dialysis. Blood Purif. 2010;29:137–144.

Introduction Kidney is the major organ for maintaining phosphate homeostasis. Hyperphosphatemia is a strong and unique risk factor for cardiovascular mortality in patients on dialysis for chronic renal failure. A comprehensive management of hyperphosphatemia is based on three principles—dietary phosphorus restriction, use of phosphate binder substances and phosphate elimination by one of several dialysis modalities.

HD Modalities Inorganic phosphorus acts like a small molecular weight uremic toxin with a distribution volume that is assumed to be equal to total body water. Due to its hydrophilic nature, the molecular weight of phosphate is considerably increased. The phosphate molecule when compared with urea cannot diffuse through the cell membrane easily. Hence, the elimination characteristics of phosphate in hemodialysis (HD) and peritoneal dialysis (PD) are dissimilar to those of urea and other small-molecular weight toxins and much more similar to those of typical middle molecules (see Fig. 1).

Phosphate Kinetics during HD During HD, blood urea nitrogen (BUN) concentrations continuously decline and, following a short rebound period immediately after termination of the treatment, steadily return to predialysis values in relation to protein intake and endogenous urea generation during the interdialytic interval. Intradialytic plasma Pi kinetics shows a characteristic 2-phase pattern. In the fi rst phase, serum phosphate levels, after an initial relatively steep decline, reach a plateau after about 2– 2.5 h into dialysis and, during the second half of the treatment, do not further decline or even slightly increase (see Fig. 1).

Dialyzer Membrane and Surface Area For any dialyzer membrane, phosphate clearance is generally lower than urea because of the higher diffusive resistance for phosphate in full blood. Membrane surface area plays an important role in phosphate mass removal. The dialyzer phosphate clearance increases with membrane surface area. Recent studies have shown that low fl ux and high fl ux membranes apparently do not differ if corrected for membrane surface area.

Blood Flow Rate and Dialysate Flow Rate Generally for any dialyzer, the clearance depends upon effective blood flow rate (QB). In contrast to urea and potassium removal, if QB is increased by >250–300 mL/ min, it has only limited effect on Pi, whereas, if dialysate fl ow rate is increased (QD) by 300–500 mL/min, then it is associated with 10% increase in Pi clearance. The use of anticoagulants such as heparin sometimes interferes with the dialytic removal of phosphate and other solutes. In a recent study, it has been demonstrated that acidifying bicarbonate-based dialysate with citrate instead of acetate may be associated with increased solute removal including phosphate.

Physical activity before or during dialysis has been shown to increase Pi removal by 6–9% and it also makes the muscle perfusion easier. Physical activity also aids to attain equilibration for urea, phosphate and other solutes. Online hemodiafi ltration (HDF) involves a signifi cant removal of uremic middle olecules and phosphate. The traditional postdilution mode and predilution mode can be applied in this therapy. Postdilution HDF has been shown to be more effective than predilution HDF. Mixed dilution may be of special advantage in patients with high predialysis hematocrit and an increased risk of fi lter clotting with postdilution HDF due to hemoconcentration. Increasing the dialysis frequency from 3 to 6 times per week provides increased quality of life and better phosphate control. Extending weekly dialysis treatment time from 12 to 15 h signifi cantly increases the phosphate removal by 13%.

Peritoneal Dialysis Modalities Hyperphosphatemia is common in both HD and PD patients and is associated with cardiovascular mortality. The phosphate anions are negatively charged and so are capillary walls and interstitial matrix. Phosphate cannot easily diffuse through the membrane when compared with urea. As a result, fl ow resistance is increased. The phosphate transport across the peritoneal membrane is infl uenced by osmotic, chemical and electrical gradients, and also by transmembrane phosphate transporters. Therefore, it is a complex process. Peritoneal Pi clearance is lower than creatinine and urea clearance in PD patients.

Renal clearance follows different characteristics for Pi clearance than creatinine and urea. The Pi clearance at the start of the dialysis is about 65%, which may decline over a period of time. The loss of renal Pi clearance can be compensated by increasing peritoneal Pi clearance due to three mechanisms. First, prescription of higher dialysate volume, second, structural changes in the peritoneal membrane with increased transport of small substances caused by the exposure to dialysis fl uid components, and third, an increase in 24-h ultrafi ltration volume with concomitantly increased convective Pi removal. Recent studies have shown that membrane transport types are characterized by peritoneal creatinine equilibration kinetics. Patients who fall under low-average and low membrane transport categories have lower peritoneal Pi clearance than those in the high- average or high membrane transport categories.

Conclusion Severe hyperphosphatemia has been associated directly with increased overall and cardiovascular mortality in HD and PD patients. The goal of normalization of serum phosphorus levels can only be reached by optimization of dialysis prescription in combination with individualized dietary and medical strategies. Management of hyperphosphatemia remains a major challenge for all subjects involved in end-stage renal disease. A variety of additional risk factors contribute to the excessive mortality, conceivably additional risk factors need to be targeted to affect the mortality.

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