Clinical factors associated with changing hematocrit levels in hemodialysis patients

The remarkable contributions Frank Gotch has made to the nephrology literat ure are celebrated in this special issue of Seminars in Dialysis. The bread th of his work in kinetics spans many areas, not the least of which was his collaboration with Dominik Uehlinger and Lewis Sheiner on the pharmacodyna mics of erythropoietin (EPO) therapy in uremic anemia (1). This paper set t he cornerstone of rational dosing of EPO in stable hemodialysis patients. I t is now seven years following its publication, and many millions of units of EPO have been delivered to patients. The rise in EPO doses from 2600 uni ts per dose in 1990 to 5400 units per dose in 1997 has raised concerns abou t EPO effectiveness (2). During the initial introduction of EPO, the origin al EPO kinetics were analyzed when patients were iron loaded Over the last seven years, there were shortages of intravenous iron in the 1991-1993 peri od, and severe iran depletion developed in EPO-treated patients (3-5). As p redicted by Dr. Gotch, dose responsiveness decreased and larger doses of EP O have ensued.