Elsevier

Blood Reviews

Volume 24, Issue 1, January 2010, Pages 39-47
Blood Reviews

REVIEW
Anemia in renal disease: Diagnosis and management

https://doi.org/10.1016/j.blre.2009.09.001Get rights and content

Summary

Chronic kidney disease (CKD) is a widespread health problem in the world and anemia is a common complication. Anemia conveys significant risk for cardiovascular disease, faster progression of renal failure and decreased quality of life. Patients with CKD can have anemia for many reasons, including but not invariably their renal insufficiency. These patients require a thorough evaluation to identify and correct causes of anemia other than erythropoietin deficiency. The mainstay of treatment of anemia secondary to CKD has become erythropoiesis-stimulating agents (ESAs). The use of ESAs does carry risks and these agents need to be used judiciously. Iron deficiency often co-exists in this population and must be evaluated and treated. Correction of iron deficiency can improve anemia and reduce ESA requirements. Partial, but not complete, correction of anemia is associated with improved outcomes in patients with CKD.

Introduction

Chronic kidney disease (CKD) affects approximately 26 million adults in the United Sates and millions of others are at risk.1 CKD is associated with significant morbidity and mortality, and these patients face many other medical problems related to CKD. One of the major medical issues facing this population is anemia, which often develops early in the course of CKD and contributes to poor quality of life. It has been shown to be strongly predictive of adverse effects, including complications and death from cardiovascular causes.2 Prior to the availability of human recombinant erythropoietin, patients receiving chronic dialysis treatment frequently required blood transfusions, exposing them to iron overload, viral hepatitis and HIV, and increasing production of antibodies to human antigens which can severely limit transplantation options.

The introduction of recombinant human erythropoietin in the late 1980s drastically changed the treatment of anemia in patients with CKD. The benefits of anemia treatment in this population reach far beyond the improvement of fatigue and decreased physical activity to a broad spectrum of physiologic functions. Thus the presence of anemia should be sought, diagnosed, and treated early in patients with CKD. The optimal hemoglobin (Hb) targets are still controversial and studies defining these goals are ongoing. The costs of anemia management in the chronic kidney disease population are considerable and need to be considered along with the risks and benefits.

Section snippets

Pathophysiology of anemia in patients with CKD

Anemia is defined by the World Health Organization as a Hb concentration less than 13.0 g/dL in adult males and non-menstruating females and less than 12.0 g/dL in menstruating females.3 Anemia is a common problem in patients with CKD, and its incidence increases as glomerular filtration rate declines. Population studies such as the National Health and Nutrition Examination Survey (NHANES) by the National Institutes of Health and the Prevalence of Anemia in Early Renal Insufficiency (PAERI) study

Evaluation of anemia in patients with CKD

As noted above, the prevalence of anemia in chronic kidney disease is as high as 10% in patients with CKD as early as stages 1 and 2. Since the consequences of untreated anemia can be severe, regular monitoring of the Hb level is needed for optimal care of this population. The 2006 National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (KDOQI) clinical practice guidelines and clinical practice recommendations for anemia in CKD advocate annual screening for anemia of all

Clinical manifestations of anemia

Anemia has a profound impact on patients with CKD. The most common symptoms are fatigue (both with activity and at rest), loss of libido, dizziness, shortness of breath, and decreased sense of well being. These symptoms generally occur when the Hb is less than 10 g/dL and become more severe as Hb levels decrease further. Other more dangerous adverse outcomes include cardiovascular disease with left ventricular hypertrophy (LVH) and congestive heart failure. These may occur when the patient is

Erythropoiesis-stimulating agents

Since the introduction of recombinant human erythropoietin in the late 1980s, ESAs have become the mainstay of treatment of anemia in patients with CKD. Treatment with ESAs corrects the underlying pathophysiology of anemia in CKD while reducing the need for transfusions and their associated complications.28 The first ESA available was epoetin alfa and it was the only therapeutic option for over 10 years. Darbepoetin alfa became available in 2001. While both are approved by the US Food and Drug

Iron therapy

Many anemic patients with CKD and inadequate EPO production have coexisting iron deficiency. Iron deficiency almost always is present in hemodialysis patients due to: bleeding when needles are removed from the vascular access, blood infiltration of the vascular access, vascular access procedures, frequent blood testing, and clotting or general blood loss in the extracorporeal circuit. The iron deficiency observed in patients with CKD not yet on hemodialysis, and those on peritoneal dialysis, is

ESA resistance

ESA resistance is defined as a failure to achieve a target hemoglobin greater than 11.0 g/dL in the setting of an epoetin alfa dose of more than 500 units/kg per week or the equivalent of another ESA. The causes can include iron deficiency, acute and chronic inflammatory conditions, severe hyperparathyroidism, aluminum toxicity, folate deficiency and PRCA. Iron deficiency is the most common cause of ESA resistance, but it is followed closely by inflammation and infection. The source of

Conclusions

Anemia is a common and important complication among patients with CKD and health care professionals should be familiar with the best practices for its screening, evaluation and treatment. Untreated anemia places patients at risk for cardiovascular events, more rapid progression of chronic kidney disease and significantly decreased quality of life. The cause of anemia is multifactorial in patients with CKD, but inadequate production of EPO by the diseased kidneys is the common denominator. The

Practice points

  • •

    Anemia is a common complication in patients with chronic kidney disease (CKD) and is associated with adverse outcomes including poor quality of life, cardiovascular disease and progression of renal failure.

  • •

    Evaluation of CKD patients with anemia is straightforward and is directed at ruling out iron deficiency and, if clinically indicated, other etiologies such as hemoglobinopathies, blood loss and vitamin deficiencies.

  • •

    Most anemic patients with CKD will have erythropoietin deficiency, which is a

Conflicts of interest

CL reports no conflicts of interest. JW has served on advisory boards for Amgen, Centocor Ortho Biotech, Watson, Affymax and AMAG, in addition to serving on speakers bureaus for Amgen, Watson, and AMAG.

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