(See also Overview of Decreased Erythropoiesis Overview of Decreased Erythropoiesis Anemia, a decrease in the number of red blood cells (RBCs), hemoglobin (Hb) content, or hematocrit (Hct), can result from decreased RBC production (erythropoiesis), increased RBC destruction... read more .)
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 Anemia of Chronic Disease The anemia of chronic disease is a multifactorial anemia. Diagnosis generally requires the presence of a chronic inflammatory condition, such as infection, autoimmune disease, kidney disease... read more — 1 General reference 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... read more ).
Other factors include
Blood loss due to dysfunctional platelets, dialysis, and/or angiodysplasia
Bone marrow resistance to EPO
Secondary hyperparathyroidism
Uremia (in which mild hemolysis is common due to an increase in red blood cell [RBC] deformity)
Less common is RBC fragmentation (traumatic hemolytic anemia Microangiopathic Hemolytic Anemia Microangiopathic hemolytic anemia is intravascular hemolysis caused by excessive shear or turbulence in the circulation. (See also Overview of Hemolytic Anemia.) Excessive shear or turbulence... read more ), which occurs when the renovascular endothelium is injured (eg, in malignant hypertension Hypertensive Emergencies A hypertensive emergency is severe hypertension with signs of damage to target organs (primarily the brain, cardiovascular system, and kidneys). Diagnosis is by blood pressure (BP) measurement... read more , membranoproliferative glomerulonephritis Membranoproliferative Glomerulonephritis Membranoproliferative glomerulonephritis is a heterogeneous group of disorders that share mixed nephritic and nephrotic features and microscopic findings. They mostly affect children. Cause... read more 
, polyarteritis nodosa Polyarteritis Nodosa (PAN) Polyarteritis nodosa is a systemic necrotizing vasculitis that typically affects medium-sized muscular arteries and occasionally affects small muscular arteries, resulting in secondary tissue... read more , or acute renal cortical necrosis Renal Cortical Necrosis Renal cortical necrosis is destruction of cortical tissue resulting from renal arteriolar injury and leading to acute kidney injury. This rare disorder typically occurs in neonates and in pregnant... read more ).
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 Amyloidosis Amyloidosis is any of a group of disparate conditions characterized by extracellular deposition of insoluble fibrils composed of misaggregated proteins. These proteins may accumulate locally... read more 
, diabetic nephropathy Diabetic Nephropathy Diabetic nephropathy is glomerular sclerosis and fibrosis caused by the metabolic and hemodynamic changes of diabetes mellitus. It manifests as slowly progressive albuminuria with worsening... read more 
) 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 Peripheral smear Anemia is a decrease in the number of red blood cells (RBCs) as measured by the red cell count, the hematocrit, or the red cell hemoglobin content. In men, anemia is defined as any of the following... read more 
, 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.
Recombinant EPO has been shown to improve anemia and reduce transfusion needs in patients with chronic kidney disease. 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. However, because there is both reduced production of EPO and marrow resistance to EPO, the recombinant EPO dose may need to be 150 to 300 units/kg subcutaneously 3 times a week. The goal is a hemoglobin of 10 to 12 g/dL (100 to 120 g/L). Careful monitoring of hemoglobin response is needed because adverse effects (eg, venous thromboembolism Deep Venous Thrombosis (DVT) Deep venous thrombosis (DVT) is clotting of blood in a deep vein of an extremity (usually calf or thigh) or the pelvis. DVT is the primary cause of pulmonary embolism. DVT results from conditions... read more 
, myocardial infarction Acute Myocardial Infarction (MI) Acute myocardial infarction is myocardial necrosis resulting from acute obstruction of a coronary artery. Symptoms include chest discomfort with or without dyspnea, nausea, and/or diaphoresis... read more 
, death) may occur when hemoglobin rises to > 12 g/dL (> 120 g/L).
In addition, adequate repletion of iron stores is required to ensure an adequate response to recombinant EPO, and concurrent iron supplementation Treatment Iron deficiency is the most common cause of anemia and usually results from blood loss; malabsorption, such as with celiac disease, is a much less common cause. Symptoms are usually nonspecific... read more 
is often needed.
In almost all cases, maximum increases in RBCs are reached by 8 to 12 weeks.
