Erythropoietin and transferrin metabolism in nephrotic syndrome.
Nephrotic syndrome is characterized by marked urinary excretion of albumin and other intermediate-size plasma proteins. This results in a profound alteration of the metabolism of many plasma proteins and protein-bound substances, as well as certain cellular and tissue proteins. This review summarizes available data on the effect of nephrotic syndrome on the metabolism and regulation of erythropoietin (EPO) and transferrin, which are essential for erythropoiesis. Studies of humans and animals have documented significant urinary losses of both EPO and transferrin in nephrotic syndrome. Urinary losses of EPO have been shown to cause EPO-deficiency anemia and prevent the normal increase in plasma EPO level in response to anemia and hypoxia in nephrotic syndrome. Similarly, transferrinuria and increased transferrin catabolism have been shown to cause hypotransferrinemia and, in some cases, iron-deficiency anemia. In addition, dissociation of iron from filtered transferrin, occasioned by a reduction in tubular fluid pH, can promote tubulointerstitial injury through the iron-catalyzed generation of oxygen free radicals. This can account in part for the role of proteinuria as a risk factor for the progression of renal disease. Subcutaneous administration of recombinant EPO has been successfully used in the management of EPO-deficiency anemia in nephrotic syndrome. Similarly, iron supplementation and nutritional support are indicated in nephrotic patients with severe transferrinuria and iron-deficiency anemia. However, correction or amelioration of the underlying proteinuria, when possible, is the ideal approach to reversal of these complications.
Vaziri
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ND
Department of Medicine, Division of Nephrology and Hypertension, University of California, Irvine, CA, USA. ndvaziri@uci.edu
D000818:Animals; D004921:Erythropoietin / Q000378:metabolism*; D006801:Humans; D009404:Nephrotic Syndrome / Q000378:metabolism* / Q000473:pathology; D014168:Transferrin / Q000378:metabolism*
D014168:Transferrin; D004921:Erythropoietin