A 56-year-old woman with polycystic kidney disease comes to the office for follow up. Her renal function has been gradually declining, and she is being considered for hemodialysis in the near future. The patient has recently experienced increasing exertional dyspnea and fatigue but has had no fever, dysuria, or flank pain. Other medical conditions include hypertension and renal calculi. Blood pressure is 130/86 mm Hg and pulse is 80/min. Physical examination shows mucosal pallor. The lungs are clear on auscultation and heart sounds are normal. Abdominal examination reveals palpably enlarged kidneys. There is no lower extremity edema. Laboratory results show normocytic, normochromic anemia, which is attributed to insufficient hormone production by the kidneys. This hormone is predominantly secreted by which of the following parts of the kidney?
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Patients with chronic kidney disease (CKD) often develop symptomatic anemia (eg, fatigue, exertional dyspnea) as the glomerular filtration rate declines. Most cases are due to the inadequate secretion of erythropoietin (EPO), a glycoprotein hormone produced by peritubular fibroblasts in the renal cortex in response to tissue hypoxia (as is seen with anemia). EPO acts on erythrocyte precursor cells (erythroid colony–forming unit cells) in the bone marrow to stimulate red blood cell differentiation and survival.
Healthy patients increase EPO levels up to 10,000-fold in response to anemia, but patients with CKD have chronic inflammatory damage to renal EPO-producing cells and are often unable to generate sufficient EPO to maintain red blood cell counts. These individuals are often treated with synthetic EPO agents (eg, epoetin, darbepoetin) to stimulate erythrocyte production. As iron is rapidly consumed to make red blood cells, individuals treated with EPO agents are often also given iron supplementation to prevent the development of iron deficiency anemia.
In adults, approximately 80% of EPO is generated in the kidney; the remainder is largely generated in the liver by hepatocytes and Ito perisinusoidal cells.
(Choices A and C) Decreased renal perfusion and glomerular filtration leads to decreased solute delivery to the juxtaglomerular apparatus in the distal tubule, which stimulates renin secretion by juxtaglomerular cells. Activation of the renin-angiotensin-aldosterone system leads to increased production of angiotensin II, a potent vasoconstrictor that preferentially constricts the efferent arteriole to restore glomerular filtration. These hormones do not have a substantial effect on red cell production.
(Choices B and E) Foot processes of renal podocytes surround glomerular capillaries to prevent filtration of large molecules (eg, plasma proteins); defects can cause chronic proteinuric kidney disease (eg, minimal change disease). Epithelial cells of the proximal tubule have a prominent role in reabsorption and secretion of solutes into the urine; these cells have high metabolic activity and are therefore susceptible to ischemic injury (eg, acute tubular necrosis) due to inadequate renal perfusion and oxygen delivery. However, neither of these cell types produces EPO.
Educational objective:
Erythropoietin (EPO) is produced primarily by peritubular fibroblast cells in the renal cortex in response to decreased renal oxygen delivery (eg, decreased blood hemoglobin content). EPO acts on erythrocyte precursor cells in the bone marrow to stimulate red blood cell production. Patients with chronic kidney disease have inflammatory damage to renal EPO-producing cells and often develop normocytic anemia due to insufficient EPO.