Joseph W. Eschbach

Iron Balance in Hemodialysis Patients

Iron deficiency is a frequent complication in chronically hemodialyzed patients because of the significant blood losses associated with this technique. Quantitating iron stores (by marrow examination or serum iron and total iron-binding capacity) on a repetitive basis had been difficult or unreliable, often resulting in failure to recognize iron deficiency superimposed on the existing anemia of chronic renal failure, or overtreating, which can lead to iron excess. Use of the serum ferritin allows easier quantitation of iron stores and, when measured serially in dialysis patients, can predict the emergence of iron deficiency. There was no correlation between serum ferritin levels and serum iron, total iron-binding capacity, or percent transferrin saturation. Iron absorption studies show that food iron absorption is physiologic, increasing when the serum ferritin is below 30 ng/ml, decreasing when more than 300 ng/ml. Treatment of iron deficiency with oral iron compounds increases serum ferritin levels and usually can maintain iron balance.

Ferrokinetics: a biologic model for plasma iron exchange in man

A method is presented for calculating internal iron kinetics. An early reflux associated with extravascular exchange and a late reflux associated with erythropoiesis are described. A biologic model of iron exchange is proposed in which erythron iron turnover is divided into an effective portion (iron fixed in circulating red cells) and wastage iron of erythropoiesis (late reflux). Nonerythroid iron exchange also has a fixed portion (parenchymal uptake) and an early reflux (lymphatic circuit), both of which correlate in amount with the amount of plasma iron. Ferrokinetic measurements in normal subjects and in various pathologic states are presented to validate the model.

The anemia of chronic renal failure in sheep. Response to erythropoietin-rich plasma in vivo.

The hypoproliferative anemia in chronic renal failure has been assumed to be the result of decreased erythropoietin (Ep) production by the damaged kidney and of the shortening of erythrocyte survival. However, many in vitro studies suggest that erythropoietic inhibitors in uremic plasma may contribute to the anemia. To determine the in vivo relevance of uremic inhibitors, increasing amounts of Ep as Ep-rich plasma were infused into six uremic sheep, and their erythropoietic responses were compared with those of nine normal sheep receiving similar amounts of Ep-rich plasma. Three sheep were studied in both normal and uremic states. Ep-rich plasma was obtained from phenylhydrazine- and phlebotomy-induced anemic sheep. Stable uremia was created by subtotal nephrectomy. Erythropoiesis was quantitated by reticulocyte response, ferrokinetics (plasma iron turnover and marrow transit time), and by hemoglobin C synthesis. Ep-rich plasma stimulated erythropoiesis similarly in uremic and normal sheep, regardless of the degree of uremia. Nondialyzed uremic sheep responded as well as dialyzed animals. The anemia was corrected in the uremic dialyzed animals. The anemia was corrected in the uremic sheep after 15-40 daily infusions of Ep-rich plasma, the total dosage depending on the severity of the anemia. Polycythemia was induced when the infusions were continued. Reticulocytes, plasma iron turnover, and erythrocyte mass changes increased as the amount of Ep-rich plasma was increased. These dose-response effects, coupled with the identical erythropoietic response in normal and uremic sheep given the same amount of Ep-rich plasma, imply that there are no physiologically significant erythropoietic inhibitors in uremia.

Improvement in the Anemia of Chronic Renal Failure with Fluoxymesterone

Abstract Fluoxymesterone was administered to 14 severely anemic patients with chronic renal failure stabilized with maintenance hemodialysis. Clinically, significant improvement in erythropoiesis w...

Iron Therapy and the Anemia of ESRD: Historical Perspective

The anemia of patients with end-stage renal disease (ESRD) is basically the same as the anemia of patients with chronic renal failure (CRF), except that in the former, additional mechanisms are unique to the dialysis patient. Customarily, the ESRD pertains only to the anemia of dialysis patients, whereas the anemia of CRF includes both the anemia observed in dialysis patients and that seen in those with progressive renal failure not yet requiring dialysis therapy. The primary etiology of CRF-related anemia is the inadequate production of the renal hormone erythropoietin (1). However, dialysis patients may have anemia accentuated by such additional factors as aluminum excess (2), severe hyperparathyroidism (3), folate deficiency (4), hemolysis related to improper dialysate solution (5), and blood loss related to the hemodialysis (HD) procedure (6). Recently, functional iron deficiency, which is related to the use of recombinant human erythropoietin (rHuEPO) therapy, has become a common cause of anemia, particularly in the HD patient (7). While the first four factors are infrequently observed, the latter two situations (chronic blood loss and functional iron deficiency) are very common. This has led to the realization that iron deficiency in the ESRD patient is a frequent complication that both aggravates anemia and reduces the ability to treat anemia optimally with rHuEPO therapy. Because iron is essential for hemoglobin (Hb) formation, this article discusses the role of iron in the pathogenesis and treatment of CRF-related anemia since the beginning of chronic (maintenance) dialysis therapy.

Hematological Problems of Renal Failure

Renal failure, whether acute or chronic, adversely affects a number of hematological parameters. Red cell production and destruction, granulocyte and lymphocyte function, platelet function and coagulation are affected to various degrees. These changes result in anemia, and an increased susceptibility to infection and hemorrhage. This chapter will deal primarily with the pathogenesis of the anemia of chronic renal failure, erythropoietin (Epo) metabolism, the treatment of this anemia with recombinant human Epo (epoetin), and the benefits of this therapy. Infection, immunological dysfunction and bleeding disorders are reviewed in Chapters 7B, 8 and 9.

A Hemodialysis Orientation Unit

A separate dialysis unit was created within an existing large dialysis unit for the purpose of segregating all new hemodialysis patients into an environment that would provide optimum instruction about self-care. An educational curriculum was presented to each patient during each dialysis over the first 2 months of dialysis. Depending upon medical condition and response to the curriculum, patients were transferred either to the home hemodialysis training unit with or without a helper, to the limited care facility, or to the general dialysis area for medically unstable patients. An orientation unit not only improves patient participation in self-care, but appears to increase the number of patients interested in dialyzing at home.

New Insights into the Treatment of the Anemia of Chronic Renal Failure with Erythropoietin

Anemia in association with chronic renal failure (CRF) has been recognized since 1836 (1). For most of the past 150 years very little was understood about this anemia. Over the past 30 years its etiology has been attributed to many factors, but only in the past 5 years has a clearer understanding of its pathogenesis emerged-partly because of the availability of erythropoietin (EP) as the recombinant hormone (rHuEP) for therapeutic, as well as for investigative, purposes. With the advent of r-HuEP as a therapeutic, anemia will eventually cease to contribute to the debility of patients with CRF. However, there are a number of issues related to how best to use r-HuEP. In addition, correction of the anemia with r-HuEP has made us more aware of the significance of the tissue hypoxia and its associated symptoms in patients with CRF. But elimination of the anemia now presents clinicians with other issues that must be addressed in order to better understand the relationship between renal endocrine and exocrine failure.

Value of Measuring Erythropoietin Levels

Does the measurement of endogenous erythropoietin levels have any role in patients with renal failure?

Use of Recombinant Human Erythropoietin in the Anemia of Progressive Renal Failure

The anemia of progressive renal failure (A/PRF) is now correctable through therapy with recombinant human erythropoietin (rHuEpo). While the prevalence of this anemia is not as great as in end-stage renal disease, its significance is greater than previously appreciated, since failure to correct this anemia can lead to disability that may not be corrected by dialysis and to unnecessary red cell transfusions. The purpose of this chapter will be to review the clinical manifestations of this anemia, its diagnosis, pathophysiology, therapy, and the beneficial and adverse consequences of rHuEpo therapy.