Anemia in nephrotic syndrome: approach to evaluation and treatment
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Nephrotic syndrome is one of the most common glomerular diseases that affect in children. Complications may occur in nephrotic syndrome as a result of the disease itself as well as its treatment. Most of these complications result from excessive urinary protein losses, and control of proteinuria is the most effective treatment strategy. Anemia is one of the many complications seen in patients with persistent nephrotic syndrome and may occur as a result of excessive urinary losses of iron, transferrin, erythropoietin, transcobalamin and/or metals. This leads to a deficiency of substrates necessary for effective erythropoiesis, requiring supplementation in order to correct the anemia. Supplementation of iron and erythropoietin alone often does not lead to correction of the anemia, suggesting other possible mechanisms which need further investigation. A clear understanding of the pathophysiologic mechanisms of anemia in nephrotic syndrome is necessary to guide appropriate therapy, but only limited evidence is currently available on the precise etiologic mechanisms of anemia in nephrotic syndrome. In this review we focus on the current state of knowledge on the pathogenesis of anemia in nephrotic syndrome.
KeywordsAnemia in nephrotic syndrome Erythropoiesis Erythropoietin deficiency Iron hemostasis Proteinuria
Answers to multiple-choice questions
1: c. Recycled iron from senescent erythrocytes is the major source of iron used for erythropoiesis with little contribution from intestinal absorption or any other sources.
2: d. Hepcidin regulates systemic iron homeostasis by causing the internalization and degradation of ferroportin, resulting in decreased iron absorption in the small intestine, recycling of iron from aged erythrocytes and iron mobilization from storage sites.
3: a. Anemia in nephrotic syndrome can result from excessive urinary losses of iron bound to transferrin and erythropoietin. This is most likely to occur in patients with persistent or treatment-resistant nephrotic syndrome. Other mechanisms may also be responsible.
4: e. Copper deficiency leads to the appearance of enlarged mitochondria in erythropoietic cells which can lead to ineffective erythropoiesis. Copper gluconate supplementation is effective in treating copper deficiency. The use of ACEIs has been associated with anemia in renal transplant patients. ACEIs may cause anemia by lowering circulating levels of erythropoietin and inhibiting erythropoiesis in the process.
5: e. The pathophysiologic mechanisms of anemia in nephrotic syndrome are complex and incompletely understood. Anemia is more likely to occur in patients with therapy-resistant, long-standing nephrotic syndrome and in the context of normal kidney function. Supplementation of iron and erythropoietin does not always lead to resolution of the anemia. Erythropoietin supplementation should be considered even in patients with normal plasma erythropoietin levels.
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Conflict of interest
The authors declare that they have no conflict of interest.
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