The recently published KDIGO (Kidney Disease: Improvement of Global Outcomes) guideline (GL) for dialysate calcium suggests a narrow range of dialysate inlet calcium concentrations (C(di)Ca(++)) of 2.50-3.00 mEq/l. The work group's primary arguments supporting the GL were (1) there is a negligible flux of body Ca(++) during dialysis and (2) C(di)Ca(++) of 2.50 mEq/l will generally result in neutral Ca(++) mass balance (Ca(MB)). We believe we have shown that both of these arguments are incorrect. Kinetic modeling and analysis of dialyzer Ca(++) transport during dialysis (J(d)Ca(++)) demonstrates that more than 500 mg of Ca can be transferred during a single dialysis and that on average 76% of this Ca flux is from the miscible calcium pool rather than plasma pool. Kinetic modeling of intestinal calcium absorption (Ca(Abs)) shows a strong dependence of Ca(Abs) on the dose of vitamin D analogs and weaker dependence on the level of Ca intake (Ca(INT)). We used the Ca(Abs) model to calculate Ca(Abs) as a function of total Ca(INT) and prescribed doses of vitamin D analogs in 320 hemodialysis patients. We then calculated total dialyzer calcium removal (TJ(d)Ca(++)) and the C(di)Ca(++) that would be required to achieve TJ(d)Ca(++)=Ca(Abs), that is, Ca(MB)=0 over the whole dialysis cycle (that is, covering both the intra- and the inter-dialytic period). The results indicate that 70% of patients on Ca-based binders and 20-50% of patients on non-Ca-based binders would require C(di)Ca(++) <2.50 mEq/l to prevent long-term Ca accumulation.