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Anemia of Renal Disease

By

Evan M. Braunstein

, MD, PhD, Johns Hopkins University School of Medicine

Last full review/revision Mar 2020| Content last modified Mar 2020

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 hepcidin suppression and increased iron sequestration (as observed in the anemia of chronic disease—1).

Other factors include

  • Uremia (in which mild hemolysis is common due to an increase in red blood cell [RBC] deformity)
  • Blood loss due to dysfunctional platelets, dialysis, and/or angiodysplasia
  • Secondary hyperparathyroidism

Less common is RBC fragmentation (traumatic hemolytic anemia), which occurs when the renovascular endothelium is injured (eg, in malignant hypertension, membranoproliferative glomerulonephritis, polyarteritis nodosa, or acute renal cortical necrosis).

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. 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) 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 simultaneous traumatic hemolysis.

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.

In patients receiving long-term dialysis, recombinant erythropoietin, beginning with 50 to 100 units/kg IV or subcutaneously 3 times a week with iron supplements, is the treatment of choice. In almost all cases, maximum increases in RBCs are reached by 8 to 12 weeks. Reduced doses of EPO (about one half the induction dose) can then be given 1 to 3 times a week. Transfusions are rarely necessary. Careful monitoring of the response is needed to avoid adverse effects when hemoglobin increases to > 12 g/dL (> 120 g/L).

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