Inorganic phosphorous acts like a small molecular weight toxin with a distribution volume equal to total body water. However, the kinetics of intradialytic phosphate removal differ significantly from classical urea kinetics. While blood urea nitrogen continuously declines during HD and, following a short rebound period immediately after termination of HD, steadily increases during the interdialytic interval, serum iP levels, after an initial relatively steep decline during the first 2-2.5 h, reach a plateau without a further decline during the second half of HD. Moreover, after termination of HD plasma iP rapidly rebounds to nearly predialysis levels [6, 7]. The intra-dialytic iP plateau predictably occurs when plasma iP baseline levels drop to about 40% of predialysis values. Since dialyzer phosphate clearance does not change during this time, these findings suggest that a substantial fraction of iP removal occurs from the intracellular space and that the transfer rate from the intracellular compartment to the plasma completely balances phosphate removal rate across the dialyzer [8].

For various reasons the average iP removal during a standard conventional 4-hour HD treatment is limited to about 700-900 mg:

(1) Dialyzer iP clearances are much higher from water and plasma than from whole blood. Unlike urea, iP is not freely diffusible across cellular membranes and thus, blood cells act like a barrier for iP diffusion, increasing the diffusion resistance for iP at the dialyzer blood side. Accordingly, intradialytic iP clearance is inversely correlated with hematocrit [9], and decreases in response to an increase in hematocrit during ultrafiltration.

(2) Membrane surface area is an important determinant of iP clearance and should be maximized in order to improve phosphate removal [10]. Limitations are set by the availability of dialyzers with larger membrane surface area.

(3) An increase in blood flow rate (Qb) to >300 ml/ min has only limited effects on phosphate removal [11].

whereas raising dialysate flow rate (Qd) is associated with a small, but significant (10%) increase in phosphorus clearance [9].

(4) Limiting treatment time to 4-5 h is the major barrier to better phosphate management. Treatment time is the most important factor governing phosphate elimination and extending treatment time increases iP mass removal even when urea-Kt/V is not changed [12]. The fact that blood iP levels reach a plateau during dialysis favors longer treatment times since, in contrast to urea, a stable concentration gradient across the dialyzer membrane is maintained throughout the second treatment phase, thereby sustaining iP mass removal. It is therefore evident that iP removal benefits much more from extended treatment times than urea removal.

(5) Phosphate removal from peripheral tissues depends on tissue, especially muscle perfusion, which may be reduced due to hypotension or peripheral atherosclerotic vascular disease. Physical activity before or during HD increases iP mass removal by 6-9% [12].

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