Anemia of Chronic Renal Failure

[cougarnurse]

Here is a good article for those of you in Dialysis-Renal nursing: Anemia of Chronic Renal Failure

The association of chronic renal failure and anemia has been recognized since the early 19th century; nowadays such a manifestation is regarded as one of the many components of the vast array of signs and symptoms present in patients with chronic renal failure. The introduction of dialysis brought new insights to this complex subject, but also added new mechanisms for the development or aggravation of such clinical picture.

The anemia of renal failure is usually characterized by normochromic and normocytic blood cells. There is usually hypoplasia of the erythroid precursors in the bone marrow with little or no interference with normal leukopoiesis and megakaryocytopoiesis. On blood smears one may find typical, although not exclusive, spiculed and deformed red cells (burr cells or echinocytes). The anemia aggravates as the renal function further declines, and the hematocrit may reach levels as low as 20% or 15%. As with any chronic anemia, compensatory mechanisms come into play in order to maintain acceptable levels of tissue oxygenation, and they consist mainly of increased levels of 2,3 DPG, lowered peripheral vascular resistance and an elevated cardiac output (in the absence of previous cardiac disease).


If the blood volume is constant, and blood loss is absent any case of anemia can only be explained by decreased production of erythroid precursors or increased destruction. Both processes seem to be operating in renal failure.

Increased destruction: Many studies have shown an inverse correlation between the red cell survival and serum blood urea nitrogen concentration. This could be demonstrated by the classical study where red blood cells from uremic individuals showed a normal life span when injected in normal individuals, the inverse (shortened red cell life span) could be demonstrated when erythrocytes from normal individuals were injected in uremic patients. The most convincing demonstration that specific toxins (not necessarily urea) were the responsible for the shortened red cell survival was obtained with the introduction of dialysis. Dialysis improved, to a limited extent, the anemia in chronic renal failure patients , although this finding could not be ascribed to prolonged red cell survival; rather, a better utilization of iron (not increased serum levels) and red cell production seemed to be determinant. The patients showed diminished transfusion requirements after initiation of a dialysis program.

Besides the mechanisms described above, the therapy itself (dialysis) can be responsible for increased destruction of red blood cells, further aggravating the anemia. Hemodialysis can worsen the anemia due to the procedure associated blood losses and mild effect on oxygen transporting function. Hypersplenism may, rarely, be associated with chronic dialysis leading to a sequestration of erythrocytes and further destruction of circulating red cells. If hypersplenism proves to be an important problem splenectomy may be considered, since it has been shown to cause a decrease in transfusion requirements.

Decreased production: Despite the mechanisms described above, the most important determinant of the anemia is failure of production due to decreased levels of circulating erythropoietin. Erythropoietin, a sialylglycoprotein synthesized by the renal interstitial cells and to a lesser extent by the liver, normally increases after specific stimuli , the most important being hypoxemia. Under normal conditions serum erythropoietin concentrations are increased by bleeding and decreased after transfusion; actually in nonuremic patients it may increase up to 100 times its normal value. In uremic patients the normal response to hypoxemia (increased secretion of erythropoietin) is partially, but not completely, blunted. These individuals show increased levels of the glycoprotein after hemorrhage or hypoxic crisis, although the levels are not even close to those of a normal individual. Therefore, the stimulus to erythropoiesis is not sufficient in uremic patients.


The mainstay of the treatment of anemic patients is the use of recombinant human erythropoietin (rHuEPO). The response to treatment is impressive and the need for transfusion is importantly decreased. Upon initiation of therapy a target hematocrit should be set as well as the iron stores should be completely evaluated (since low stores may blunt the proliferative response to erythropoietin). The beginning of therapy should be gradual to avoid excessively rapid increases in the red cell mass with its hyperviscosity consequences. A total weekly dose of 110 to120 U/kg divided into two or three subcutaneous injections is an adequate thaerapeuric regimen.

Transfusions should be avoided as much as possible, not only because of the well known infectious risks and the fluid overload in cardiac patients but also to avoid inhibition of the low, although present, positive feedback on erythropoietin secretion exerted by chronic hypoxemia. Other possible deficiencies should be assessed before therapy is started such as, vitamin B12 deficiency, folate deficiency or aluminum intoxication (this latter leading to microcytic anemia). Throughout the course of therapy, iron stores(serum iron, ferritin and TIBC) should be determined frequently, since the rapid proliferative response may not be accompanied be an adequate availability of iron. If the iron stores are proved insufficient during the course of therapy, replacement should be started without delay.

A number of adverse effects have been documented in patients receiving rHuEPO. Myalgias and influenza-like symptoms may occur. The occurrence of seizures remains an unsettled issue, with some defending a causal relationship ,while others argue against this hypothesis suggesting that these neurological phenomena are due to imbalances in dialysis therapy.

Thrombotic events ARE NOT increased with the use of rHuEPO , although clotting within the dialyser may occur. Of the adverse effects found with the use of rHuEPO, hypertension is without any doubt the most important not only in terms of frequency but also morbidity. Occurring in approximately 30% to 35%, hypertension usually occurs in the first 4 months of treatment while the hematocrit is increasing. The exact mechanism of hypertension is not defined yet but it may be so severe as to cause hypertensive encephalopathy with headache, visual disturbances and seizures. Uncontrolled hypertension is a contraindication to the initiation of therapy with rHuEPO. Hypertension is not dependent on the dose of rHuEPO or the rate of hematocrit increase.