A Kinetic Model of Inorganic Phosphorus Mass Balance in Hemodialysis Therapy

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.