Determinants of the serum phosphate concentration in chronic kidney disease

Abstract

If C_cr is creatinine clearance and E_P and TR_P are rates of phosphate excretion and reabsorption, the serum phosphate concentration (P_s) is the sum of E_P/C_cr and TR_P/C_cr, i.e., the amounts of phosphate excreted and reabsorbed per volume of filtrate. At equilibrium, influx of phosphate into plasma determines E_P, and E_P/C_cr quantifies the contribution of phosphate influx to P_s. We used data obtained at 688 clinic visits of 387 patients to analyze the evolution of P_s in chronic kidney disease (CKD) stages G1 - 5 (dialysis excluded). E_P/C_cr was calculated as (P_u×cr_s)/cr_u and TR_P/C_cr as P_s-E_P/C_cr (where u is urine, s is serum, and cr is creatinine). Means of these parameters were plotted against CKD stages, and correlations among variables were determined with regression analyses. In comparison to values in CKD stages G1 - 2, E_P/C_cr rose and TR_P/C_cr fell by the same amount in CKD G3a and G3b, and P_s did not change. In stages G4 and G5, E_P/C_cr increased sharply, TR_P/C_cr fell minimally, and P_s rose significantly. At estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73m², TR_P/C_cr was the principal determinant of P_s at eGFR < 45 mL/min/1.73m², contributions of E_P/C_cr and TR_P/C_cr to P_s were comparable. Taken together, our results show that in CKD stages G4 and G5, the effect of phosphate reabsorption on P_s changes negligibly while that of phosphate influx increases dramatically. Because the tubular response to rising E_P/C_cr is limited, maintenance of stable P_s in advanced CKD requires extreme reduction of phosphate influx into plasma. TR_P/C_cr may define the lowest attainable P_s.