Chapter 38 - Nutrition and anemia in chronic kidney disease

Abstract

Anemia is a highly prevalent complication in patients with chronic kidney disease (CKD) and its severity and prevalence increase with increasing CKD severity. Many factors contribute to anemia in CKD, of which a hallmark feature is erythropoietin deficiency. The availability of erythropoietin-stimulating agents (ESAs) has revolutionized anemia management in CKD patients in the last two decades. However, the cardiovascular safety of ESA treatment in CKD came into question some years ago when ESA trials that targeted hemoglobin (Hb) >13g/dL showed greater risks for death, cardiovascular events, and stroke than a lower Hb target. This led to revision of the recommended Hb target by the different international guidelines to no more than 11.5–12g/dL for CKD 3–5D patients. On the other hand, the discovery of the hypoxia-inducible factor (HIF) transcription complex in 1992 has unfolded important novel mechanisms that regulate erythropoietin gene and erythropoietin production in the kidneys in response to hypoxia or anemia. This led to development of a new class of drugs called HIF stabilizers, or HIF prolyl hydroxylase domain (PHD) inhibitors that prevent the proteasomal degradation of HIF-α, thereby inducing upregulation of erythropoietin gene. The PHD inhibitors can be orally administered and represent a novel paradigm for anemia management in CKD. Currently, several of them are undergoing phase III clinical trials in adults. The PHD inhibitors may have better cardiovascular safety profile in that they induce lower erythropoietin production, lower hepcidin levels, increase iron absorption and mobilization, lower cholesterol level, and have a neutral effect on blood pressure than ESA. However, the long-term safety of this new class of drugs remains to be tested as the PHD inhibitors also stimulate angiogenic factors such as vascular endothelial growth factor and glycolytic factors. In this chapter, we also review other key nutrition factors involved in anemia in CKD, including iron, carnitine, vitamin C, vitamin D, folate, and several other B group vitamins. We specifically review iron homeostasis, iron balance and management, interrelations between the HIF pathway and iron, and hepcidin. We also discuss erythropoietin hyporesponsiveness in CKD patients.