Overview of anemia associated with chronic renal disease: primary and secondary mechanisms

Abstract

The development of hypoproliferative anemia with generally normocytic red blood cells in most patients with chronic renal failure impairs the success of maintenance dialysis therapy, particularly hemodialysis. Anemia can be a complication of the hemodialysis procedure itself, with its associated blood losses and mild effect on oxygen transport functioning. However, the primary cause of anemia in the chronic dialysis patient is decreased erythropoiesis. The most important mechanism leading to decreased erythropoiesis involves the production of subnormal levels of erythropoietin (EPO). Insufficient nephric output of EPO or, possibly, suppression of the effect of EPO by uremic inhibitors may cause this decreased erythropoiesis. Other factors, such as iron deficiency, hyperparathyroidism, systemic infections, and aluminum toxicity may contribute to anemia in some patients. Increased hemolysis, a comparatively mild factor in the anemia of chronic dialysis patients, may be related to retention of protein metabolism products, hypersplenism, hypophosphatemia, drugs, or other conditions in affected patients. There are several traditional treatment options for anemia: transfusions; iron, vitamin B12, or folic acid supplementation when indicated; a change to peritoneal dialysis; parathyroidectomy; and administration of androgens. None of these treatments have proved satisfactory, and some, such as transfusions and androgen therapy, pose risks and have serious side effects. A comparatively new approach, administration of genetically engineered erythropoietin (r-HuEPO; EPOGEN, AMGEN inc, Thousand Oaks, CA), has been found effective in treating anemia in clinical trials. Patients have shown improved cardiac performance as well as enhanced quality of life, and hypertension appears to be the most serious side effect of r-HuEPO therapy.