Anemia of renal disease is a hypoproliferative anemia resulting primarily from deficient erythropoietin (EPO) or a diminished response to it; it tends to be normocytic and normochromic. Treatment includes measures to correct the underlying disorder and supplementation with EPO and sometimes iron.
(See also Overview of Decreased Erythropoiesis.)
Anemia in chronic renal disease is multifactorial.
The most common mechanism is
Hypoproliferation due to decreased erythropoietin (EPO) production
Lack of EPO leads to loss of erythroferrone production, causing loss of hepcidin suppression and increased iron sequestration (as observed in the anemia of chronic disease—1).
Other factors include
Blood loss due to dysfunctional platelets, dialysis, and/or angiodysplasia
Bone marrow resistance to EPO
Secondary hyperparathyroidism
Uremia (leading to shortened red blood cell [RBC] survival)
The deficiency in renal production of EPO and the severity of anemia do not always correlate with the extent of renal dysfunction; anemia occurs when creatinine clearance is < 45 mL/minute (< 0.75 mL/s/m2). Renal glomerular lesions (eg, due to amyloidosis, diabetic nephropathy) generally result in the most severe anemia for their degree of renal excretory failure.
General reference
1. Kautz L, Jung G, Valore EV, et al: Identification of erythroferrone as an erythroid regulator of iron metabolism. Nat Genet 46:678–684, 2014. doi: 10.1038/ng.2996
Diagnosis of Anemia of Renal Disease
Complete blood count (CBC), reticulocyte count, and peripheral smear
Diagnosis of anemia of renal disease is based on demonstration of renal insufficiency, normocytic anemia, and peripheral reticulocytopenia.
The bone marrow may show erythroid hypoplasia. RBC fragmentation identified on the peripheral smear, particularly if there is thrombocytopenia, suggests microangiopathic hemolytic anemia and warrants additional investigation and treatment.
Treatment of Anemia of Renal Disease
Treatment of underlying renal disease
Sometimes, recombinant erythropoietin and iron supplements
Treatment of anemia of renal disease is directed at
Improving renal function
Increasing RBC production
If renal function returns to normal, anemia is slowly corrected.
venous thromboembolism, myocardial infarction, death) may occur when hemoglobin rises to > 12 to 13 g/dL (> 120 to 130 g/L). Lower doses of EPO are used in patients with chronic kidney disease who are not on dialysis.
In addition, adequate repletion of iron stores is required to ensure an adequate response to recombinant EPO, and concurrent iron supplementation is often needed. The addition of IV iron is considered in patients with hemoglobin < 10 g/dL (< 100 g/L), ferritin ≤ 500 ng/mL (< 500 micrograms/L), and transferrin saturation (TSAT) ≤ 30%.
In almost all cases, maximum increases in RBCs are reached by 8 to 12 weeks.
1); however, long-term safety data are lacking.
Treatment reference
1. Singh AK, Carroll K, Perkovic V, et al: Daprodustat for the Treatment of Anemia in Patients Undergoing Dialysis. N Engl J Med 2021;385(25):2325-2335. doi:10.1056/NEJMoa2113379
