A 64-year-old man comes to the office for follow-up. He has a history of chronic kidney disease due to hypertensive and diabetic nephropathy. Six months ago, he developed significant fatigue and exercise intolerance. Evaluation at that time revealed normocytic anemia and normal serum iron studies so recombinant erythropoietin was initiated. Today, the patient states that his symptoms have significantly improved. Laboratory evaluation reveals a hemoglobin of 12 g/dL. If the erythropoietin treatment is continued, this patient is at greatest risk for which of the following complications?

Question

A 64-year-old man comes to the office for follow-up.  He has a history of chronic kidney disease due to hypertensive and diabetic nephropathy.  Six months ago, he developed significant fatigue and exercise intolerance.  Evaluation at that time revealed normocytic anemia and normal serum iron studies so recombinant erythropoietin was initiated.  Today, the patient states that his symptoms have significantly improved.  Laboratory evaluation reveals a hemoglobin of 12 g/dL.  If the erythropoietin treatment is continued, this patient is at greatest risk for which of the following complications?

Quizplus · Accepted Answer

Erythropoietin (EPO) promotes the survival, differentiation, and proliferation of immature erythrocytes. It is produced by interstitial fibroblasts near the peritubular capillaries of the kidney in response to hypoxia; deficiency often occurs in the setting of chronic kidney disease due to inflammatory damage to the peritubular interstitial fibroblasts. Patients with EPO deficiency generally present with normocytic anemia, low reticulocyte count, and iron studies similar to those seen in anemia of chronic disease (eg, low serum iron, low/normal total iron-binding capacity). Treatment with recombinant EPO restores the stimulus for erythropoiesis, increases hemoglobin, and improves tissue oxygen delivery. However, prolonged use of EPO can lead to serious morbidity, including the following: Thromboembolism: EPO increases blood viscosity and triggers the release of proinflammatory cytokines from the endothelium, which increases the risk for thromboembolism. It also promotes the release of procoagulant proteins such as von Willebrand factor and plasminogen activator inhibitor-1. Hypertension: EPO increases systemic vascular resistance, possibly due to activation of erythropoietin receptors on vascular endothelial and smooth muscle cells. This can result in hypertensive encephalopathy and increased risk of cardiovascular events (eg, stroke, myocardial infarction). To avoid morbidity, most studies recommend cessation of recombinant EPO once hemoglobin improves to 12-13 g/dL; attempting to increase hemoglobin >13 g/dL increases the risk of adverse effects and death. (Choice A) Autoantibodies can form against recombinant EPO, which limits its efficacy. However, recombinant EPO does not typically trigger autoantibodies against erythrocytes; therefore, hemolytic anemia would be atypical. (Choice B) Recombinant EPO may worsen malignancy due to the promotion of vascular growth. It does not typically cause myelofibrosis or myeloproliferative disorders. However, these conditions may be triggered by the use of granulocyte colony-stimulating hormone due to excessive stimulation of granulocyte stem cells. (Choice C) The use of recombinant EPO does not usually increase bilirubin and does not typically cause gallstones. Increased risk of gallstones can be seen with some causes of anemia such as sickle cell disease and thalassemia. (Choice D) Recombinant EPO stimulates erythrocytosis, which can rapidly consume iron stores (it does not cause iron overload). Therefore, iron levels should be monitored before and during treatment to ensure that iron deficiency does not occur. Educational objective: Patients with chronic kidney disease often develop normocytic anemia due to erythropoietin (EPO) deficiency. Treatment with recombinant EPO can dramatically improve tissue oxygen delivery and reduce mortality. However, prolonged or high-dose treatment can have serious side effects, most notably increased risk of hypertension and thromboembolism. __________ References: Clinical use of erythropoietin in chronic kidney disease: outcomes and future prospects. (http://www.ncbi.nlm.nih.gov/pubmed/22110290)

A 64-Year-Old Man Comes to the Office for Follow-Up