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These preliminary analyses suggest that it may be possible to reliably model and predict Ca balance during dialysis. It must be emphasized, however, that the model must be validated in patients with appropriate in vivo studies of mass balance measurements which are guided by the model.

It will also be essential to obtain measurements of interdialytic Ca balance as a function of dietary and binder Ca intake which will require metabolic ward studies.

The model suggests that we are at present routinely loading Ca during dialysis in most patients, which, with or without use of CaCO3 binders, would appear to be inappropriate management of Ca/P balance in these pa-

A Estimated predialysis Ca2+, mEq/L

500 400

500 400

-800

0 10 20 30 40 50 60 70 80 90 100 B Cumulative % of patients

-800

0 10 20 30 40 50 60 70 80 90 100 B Cumulative % of patients

Fig. 14. A Frequency distribution of calculated CpCa in FMC patients compared to normal subjects and the current standard CdiCa. Simple inspection of the data indicates that there is substantial uptake of Ca from the dialysate during dialysis in virtually all patients. Is this optimal therapy? B Modeled Ca balance during dialysis calculated as a function of CdiCa2+ and the frequency distribution of CopCa2+ in FMC patients. Note that Ca balance is positive in nearly all patients when CdiCa = 2.5 mEq/l. What should Ca balance be? There are no clinical guidelines at this time because there are no overall mass balance data.

tients. It does not intuitively make sense that we should be providing positive Ca balance during dialysis to essentially all our patients [5]. It would seem likely that with widespread use of vitamin D analogues and normal to high dietary protein intakes there may be a substantial amount of Ca absorption from diet and binders which would logically mandate negative Ca balance during dialysis for optimal management of mineral metabolism in these patients. There is a high rate of vascular calcification which may to a considerable extent be due simply to mismanagement of Ca and P balance with chronic overloads of both Ca and P [5]. As noted above, the Ca loading is directly proportional to treatment time so that the use of longer treatment time to increase PO4 removal will also result in increased Ca loading with current therapy unless there is appropriate adjustment of CdiCa. Substantial improvement in clinical outcome might result from the validation of the model and its clinical use to control mass balance in dialysis therapy. The model could also possibly provide a novel experimental tool to evaluate the effects of acute quantified levels of net positive and negative Ca balance on PTH for example. It can be used to remove substantial amounts of Ca with CdiCa2+.

We will proceed with in vitro studies already underway with aqueous solutions of bovine plasma and bovine whole blood to characterize dialysance of Ca with the FMC low- and high-flux dialyzers. Once we have these numbers we plan to promptly start in vivo studies with the model at RRI. Initial protocols have been written for these studies.

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