The optimal method for diagnosing iron deficiency in end-stage renal disease is an area of controversy. This study compared the use of zinc protoporphyrin (ZPP) with the use of conventional tests for determination of iron deficiency when evaluating the need for intravenous iron therapy in hemodialysis patients maintained on erythropoietin (EPO). A baseline survey was performed in all hemodialysis patients at the Baumritter Kidney Center (Bronx, NY), measuring ZPP, ferritin, transferrin saturation (TSAT), mean corpuscular volume, and hematocrit. Patients with ZPP > or = 90 mumol/mol heme or ferritin less than 100 ng/mL were considered likely to be iron deficient and were treated with 1,000 mg of intravenous iron dextran over 10 hemodialysis treatments. The positive predictive values of ferritin and ZPP for predicting a response to intravenous iron dextran were similar (73% v 83%, respectively; two-tailed, P = 0.48). To determine the sensitivity and specificity of the tests, patients were divided into two groups at the end of the study period: those in whom iron therapy was required (n = 23) (patients treated with intravenous iron dextran who had a 5% increase in hematocrit or a decrease in erythropoietin dose of > or = 2,000 U/treatment) and those in whom iron therapy was not required (n = 24) (patients either treated with intravenous iron dextran without a response [n = 9] or patients whose initial ZPP and ferritin levels were not suggestive of iron deficiency and who maintained a stable hematocrit and erythropoietin dose during the study period [n = 15]).(ABSTRACT TRUNCATED AT 250 WORDS)