Background: There is growing evidence that inorganic phosphorus (iP) accumulation in tissues (dTiP/dt) is a risk factor for cardiac death in hemodialysis therapy (HD). The factors controlling iP mass balance in HD are dietary intake (GiP), removal by binders (JbiP) and removal by dialysis (JdiP). If iP accumulation is to be minimized, it will be necessary to regularly monitor and optimize GiP, JbiP and JdiP in individual patients. We have developed a kinetic model (iPKM) designed to monitor these three parameters of iP mass balance in individual patients and report here preliminary evaluation of the model in 23 HD patients. Methods: GiP was calculated from PCR measured with urea kinetics; JdiP was calculated from the product of dialyzer plasma water clearance (K_pwiP) and time average plasma iP concentration (TACiP) and treatment time (t); a new iP concentration parameter (nTAC_iP, the TACiP normalized to predialysis CoiP) was devised and shown to be a highly predictable function of the form nTAC_iP = 1 – α(1 – exp[–βK_pwiP· t/ViP]), where the coefficients α and β are calculated for each patient from 2 measure values for nTAC_iP, K_pwiP·t/ViP early and late in dialysis; we measured 8–10 serial values for nTAC_iP, K_pwiP· t/ViP over a single dialysis in 23 patients; the expression derived for iP mass balance is ΔTiP = 12(PCR) – [K_pwiP(t) (N/7)][CoiP(1 – α(1 – exp[–β(Kt/ViP)]))] – k_b·Nb. Results: Calculated nTAC_iP = 1.01(measured nTAC_iP), r = 0.98, n = 213; calculated JdiP = 0.66(measured total dialysate iP) + 358, n = 23, r = 0.88, p < 0.001. Evaluation of 10 daily HD patients (DD) and 13 3 times weekly patients with the model predicted the number of binders required very well and showed that the much higher binder requirement observed in these DD patients was due to much higher NPCR (1.3 vs. 0.96). Conclusion: These results are very encouraging that it may be possible to monitor the individual effects of diet, dialysis and binders in HD and thus optimize these parameters of iP mass balance and reduce phosphate accumulation in tissues.

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We conclude that (1) the osmotic Na distribution volume in blood is total blood water; (2) K(ecn) measured with a short, high/low, and asymmetric dialysate profile shows R(ac) effect but neither R(cp) nor R(s) effects on K(ecn) and K(ecn)/K(eu)= 1.0; (3) the K(ecn)/K(eu) ratio is strongly dependent on the type of dialysate profile used, which must be optimized to minimize net Na transfer to and from blood during measurement of conductivity clearance to avoid erroneous underestimation of K(ecn) and K(ecn)/K(eu) ratios <1.

In vivo solute clearances can be estimated from dialyzer blood (Qb) and dialysate (Qd) flow rates and a solute- and dialyzer-specific overall permeability membrane area product (KoA). However, these calculations require knowledge of the flow rate of the effective solute distribution volume in the flowing bloodstream (Qe) in order to calculate in vivo clearances and KoAs. We have determined Qe for urea, creatinine, and inorganic phosphorus from changes in concentrations across the blood compartment and mass balance between the blood and dialysate streams. We made four serial measurements over one dialysis in 23 patients and found that Qeu equals the total blood water flow rate, Qecr equals the plasma water flow rate plus 61% of red cell water flow rate, and QeiP is limited to the plasma water flow rate. Equations are derived to calculate Qe for each of these solutes from Qb and hematocrit and in vivo KoAs for each solute were calculated.