Steven Fishbane

Reduction in recombinant human erythropoietin doses by the use of chronic intravenous iron supplementation.

We have compared the efficacy of oral to intravenous iron for the chronic maintenance of iron stores in hemodialysis patients. Fifty-two hemodialysis patients with initial serum ferritin greater than 100 ng/mL and transferrin saturation greater than 15% were randomly assigned to one of two groups: those receiving oral iron therapy (n = 32) and those receiving intravenous iron dextran (100 mg twice weekly) (n = 20). At study completion (4 months), the mean hematocrit was significantly higher in the intravenous group than in the oral iron group (34.4% +/- 0.7% v 31.8% +/- 0.4%, respectively; P < 0.05), the final mean recombinant human erythropoietin dose was 46% lower in the intravenous iron group than in the oral group (4,050 +/- 634 U/treatment v 7,563 +/- 378 U/treatment; P < 0.05), and the mean serum ferritin was significantly higher in the intravenous group than in the oral iron group (753.9 +/- 30.2 ng/mL v 157.3 +/- 15.4 ng/mL, respectively; P < 0.05). We have found that administering iron intravenously instead of orally for chronic maintenance iron supplementation in hemodialysis patients resulted in improved erythropoiesis. We hypothesize that most hemodialysis patients have inadequate iron stores for optimal erythropoiesis when currently recommended levels of ferritin and transferrin saturation are used to guide therapy, and that the chronic use of intravenous iron could reduce recombinant human erythropoietin requirements by maximizing iron stores. The improvement in erythropoiesis was accompanied, however, by an increase in iron indices to levels that could be indicative of tissue iron overload. Future studies must be performed to determine whether lower doses of intravenous iron dextran would improve erythropoiesis without causing potential organ iron overload.

Iron management in end-stage renal disease

One of the important components of successful anemia therapy in patients with end-stage renal disease (ESRD) treated with recombinant human erythropoietin is the maintenance of adequate available iron. To accomplish this task, iron status must be serially monitored and supplemental iron administered as required. Among nonuremic subjects, the bodys iron supply is tightly conserved, and iron deficiency usually develops only when chronic blood loss occurs. In patients with ESRD, iron deficiency occurs more frequently, because of increased external losses of iron, decreased availability of the bodys storage of iron, and perhaps a deficit in intestinal iron absorption. Detecting iron deficiency in these patients can be difficult because of the inaccuracy of available diagnostic tests. The goals of iron therapy in ESRD include the prevention of iron deficiency by chronically supplementing iron, and the prompt treatment of overt iron deficiency. Oral iron supplements are inexpensive and safe, but poor patient compliance and reduced intestinal absorption may limit their effectiveness. Intravenous iron supplements have a greater efficacy then oral iron, which must be weighed against the small risk of allergic reactions. We present strategies for using the various diagnostic tests and treatment modalities to effectively manage iron supply for predialysis, hemodialysis, and peritoneal dialysis patients.

Ankle-arm blood pressure index as a marker for atherosclerotic vascular diseases in hemodialysis patients

The ankle to arm blood pressure index (AABI) has been recently found to be a strong predictor of cardiovascular and overall mortality in several populations. The test, which is a noninvasive marker for lower extremity vascular disease (when the index is < 0.9), is an office procedure that is simple to perform. The purpose of this study was to evaluate the AABI in hemodialysis patients. One hundred seventy-seven hemodialysis patients were studied, of which the AABI could be measured in 142. The AABI was then compared in patients with and without coronary artery disease, cerebrovascular disease, and peripheral vascular disease. In patients with or without coronary artery disease, the AABI was, respectively, 0.87 +/- 0.03 and 1.03 +/- 0.02 (P < 0.0001). For cerebrovascular disease, the mean AABI for patients with or without disease was, respectively, 0.82 +/- 0.04 and 1.00 +/- 0.02 (P < 0.0004). In patients with or without peripheral vascular disease, the mean AABI was, respectively, 0.75 +/- 0.04 and 1.02 +/- 0.02 (P < 0.0001). The mean AABI was 0.86 +/- 0.03 in patients with any of the three diseases compared with 1.07 +/- 0.02 in patients without any vascular disease (P < 0.0001). Thirty-eight percent of patients had an AABI of less than 0.9; 24% were less than 0.8 and 11% were less than 0.7.(ABSTRACT TRUNCATED AT 250 WORDS)

Proximal calciphylaxis in four insulin-requiring diabetic hemodialysis patients

We present four cases of proximal calciphylaxis in end-stage renal disease patients treated with hemodialysis. All patients were diabetic and developed lesions in areas that had previously served as sites of insulin injection. We review the presentation, pathogenesis, pathology, prognosis, and treatment of this devastating condition. Finally, we hypothesize that subcutaneous injection of insulin may play a pathogenic role in the development of proximal calciphylaxis.

The utility of zinc protoporphyrin for predicting the need for intravenous iron therapy in hemodialysis patients.

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)

Anemia and Cardiovascular Risk in the Patient with Kidney Disease

Patients with chronic kidney disease (CKD) often experience anemia, which causes fatigue and diminished quality of life. In addition, anemia in CKD has been associated with increased risk for cardiovascular events and left ventricular hypertrophy. To the extent that anemia plays a causal role in these relationships, treatment with erythropoiesis-stimulating agents (ESAs) could potentially help improve outcomes. To date, however, results from interventional studies have been disappointing in this regard. This article reviews the relationship between anemia in CKD and cardiovascular risk and explores current knowledge on ESA treatment.

A Consensus on Current Issues and Controversies in Iron Management of Patients with Chronic Renal Failure

The objective of the consensus panel was to review existing literature on iron management in chronic renal failure (CRF) patients relative to the National Kidney Foundation–Dialysis Outcomes Quality Initiative (NKFDOQI) Anemia Guidelines in order to help guide clinicians in improving outcomes in CRF patients. Participants on the panel were leading nephrologists and research clinicians. The panel meeting was convened on October 5, 1997. The participants’ expertise includes physiology of renal disease and anemia, iron metabolism, management of anemia of chronic renal disease, and quality-of-life issues related to treatment. The group reviewed evidence in the existing literature on major topics: lessons learned during clinical trials and since recombinant human erythropoietin (rHuEPO) therapy became commercially available in 1989; iron physiology and metabolism; potential consequences of iron overload; effect of elevated iron levels on morbidity; use of oral iron versus intravenous (IV) iron; and riskbenefit ratio of IV iron. The strength of the evidence was reviewed in relation to the NKF-DOQI Anemia Guidelines. Potential barriers to implementing these guidelines were discussed and recommendations were made on the basis of the evidence presented. According to our current knowledge, no valid barriers exist to the implementation of the NKF-DOQI Anemia Guidelines. To date, no convincing evidence suggests that iron overload and tissue deposition, increased risk of infection or cardiovascular disease, or adverse events should dissuade physicians from following the guidelines. Several areas warrant additional research: studies of iron deposition in cardiac tissue in patients receiving only iron dextran; examination of the effect of repeated administration of IV iron dextran on tissue deposition in renal dialysis patients (through autopsy studies); and determination of whether correction of iron deficiency with IV iron can improve cognitive function and quality of life, independent of its effect on hematocrit or hemoglobin.