A 36-year-old woman with end-stage renal disease secondary to type 1 diabetes mellitus comes to the office for routine examination. The patient's medical history includes hypertension, diabetic retinopathy, and neuropathy. Hemodialysis was started 2 months ago along with an erythropoiesis-stimulating agent. She takes daily long- and short-acting insulin, lisinopril, and calcitriol. Her hemoglobin has increased from 7.4 g/dL to 10.2 g/dL over the past 2 months. Which of the following complications is most likely to be seen with the agent used to treat this patient's anemia?
Erythropoiesis-stimulating agents (ESAs) (eg, erythropoietin, darbepoetin alpha) can be used to treat anemia of chronic kidney disease (CKD), which usually develops at a glomerular filtration rate of <30 mL/min. Untreated anemia in CKD and dialysis patients can lead to cardiac dysfunction, fatigue, weakness, and possible mental status changes (eg, decreased cognition). ESAs can substantially improve anemia, avoiding the need for blood transfusions. However, ESAs are associated with increased risk for thromboembolic events (eg, vascular graft thrombosis, stroke) due to increased blood viscosity, as a result of the elevation in red cell mass. Many patients also develop hypertension, possibly due to activation of erythropoietin receptors on vascular endothelial and smooth muscle cells.
(Choice A) Angioedema is a possible side effect of lisinopril, an ACE inhibitor. ACE inhibition causes impaired inactivation of bradykinin (a vasoactive peptide), leading to vasodilation, hypotension, and possible angioedema.
(Choices B and D) Iron supplements can cause constipation, diarrhea, nausea, and epigastric pain. Long-acting insulin is usually cleared by the kidneys and can predispose CKD patients to hypoglycemia. However, ESAs are usually not associated with diarrhea or hypoglycemia.
(Choice C) Hyperkalemia is a frequent complication of acute kidney disease and CKD. However, it is not a common side effect of ESAs.
(Choice E) Mineral bone disease can be a complication of CKD due to secondary hyperparathyroidism, leading to calcium loss from bone. However, it is not a side effect of this patient's medications.
Educational objective:
Erythropoiesis-stimulating agents (ESAs) can substantially improve anemia symptoms, avoiding the need for blood transfusions in chronic kidney disease and dialysis patients. However, ESAs are associated with increased risk for hypertension and thromboembolic events.