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Anemia in chronic renal failure.

This article was first published in The Canadian Society of Extracorporeal Circulation Technicians The/Le Journal (1973, March), 2(1), 17-18.

Richard Bright, in 1836, commented on the characteristic pallor of patients with nephritis (Bright, 1836), and this symptom has become a hallmark of chronic renal failure. Our experience in chronic hemodialysis has demonstrated clearly that anemia is a very serious aspect of the uremic syndrome. Because its prevention is difficult, and its treatment is complicated by many hazards, it is an important symptom to consider. This paper represents a brief review of the causes, symptoms and methods of treatment of the anemia of chronic renal failure.


Most authors describe three major causes of uremic anemia: blood loss, hemolysis and shortened red cell survival, and failure of the bone marrow to produce new red cells (Schreiner & Maher, 1961; Brest & Moyer, 1967; Adamson, Eschbach, & Finch, 1968).

The loss of red cell mass can occur in a variety of ways, chief among them being hemorrhage and complications of dialysis. Schreiner and Maher wrote in 1961 that abnormal bleeding was unquestionably a major complication of uremia. They reported the most frequent abnormalities to be centred around platelets, with thrombocytopenia and abnormal prothrombin consumption being well documented (Schreiner & Maher). However, a 1967 report by Hampers and Schupak states that chronic hemodialysis patients do not manifest a bleeding tendency, and, in fact, they found evidence exists that some patients may be in a 'hypercoagulable state' and require anti-coagulants to prevent shunt clotting (Hampers & Schupak, 1967).

There is no doubt about the dangers of blood loss through chronic hemodialysis. Retention of blood in the dialyzer at the end of the procedure, frequent sampling for laboratory tests, membrane leaks, and abnormal bleeding resulting from anticoagulation are all sources of blood loss. The systemic causes of anemia rarely result in iron deficiency, but chronic loss of blood, over a period of months or years of dialysis, may deplete iron stores as well.

The red blood cells in uremic patients are often deformed and, when the changes are pronounced, the cell's life span is shortened and hemolysis ensues. In the majority of patients, this shortened life span is related to the unfavourable environment of uremia, rather than to the fault in the cells themselves. Although the decrease in viability is usually quite moderate, in combination with defective bone marrow compensation, it may lead to a significant degree of anemia (Brest & Moyer). Hemolysis and lack of erythropoiesis play varying roles in their relation to the uremic blood picture.

As with the renin-angiotensin system, there is another renal factor that acts on a plasma substrate to produce an active end product. This erythropoietin apparently acts on the bone marrow by stimulating the conversion of primitive undifferentiated cells to erythroblasts. The anatomic location of erythropoietin-producing cells is not known. Evidence that the renal factor may be produced in the JG Apparatus is inconclusive. Erythropoietin is sensitive to slight changes in oxygen supply. It is normally present in urine, and the output changes in hematocrit levels. (Experimentally, erythropoietin appears to rise as hematocrit falls.) Lack of erythropoietin results in a lack of stimulation and proliferation of the erythroid marrow and subnormal red cell level.

In some patients, chronic urinary tract infection serves to further depress the erythropoietin mechanism. There is also evidence that the toxins produced by uremia depress the production of red cells in the bone marrow (March, Dr. A.C., Personal Communication).

The concept of erythropoietin failure in renal disease is complicated in that certain diseases its production is increased rather than decreased. This occurs when lesions produce renal ischemia without severely damaging the erythropoietin-generating apparatus, such as experimentally increasing intrarenal pressure by ureteral obstruction. Neoplastic lesions of the kidney may also cause an excess production of erythropoietin leading to an increase in red cell mass.

There is evidence to suggest some extra-renal production of erythropoietin. However, the important role of the kidney is demonstrated by the increased hematocrit of a renoprival patient following a successful transplant.

In summary, the kidney is the primary organ responsible for the regulation of erythropoiesis. Renal failure is often associated with a decreased erythropoietin output resulting in hypoproliferative anemia. In addition, a moderate degree of hemolysis and blood loss by various means plays an important role in decreasing red cell mass, which the bone marrow is unable to restore to normal.


Aside from the characteristic pallor, the primary symptom of uremic anemia is fatigue or loss of strength. Some patients are well able to tolerate hematocrit levels below 20% and remain relatively asymptomatic. Older patients and those who have significant myocardial hypertrophy, hypertension and hypertensive cardiovascular disease may require higher hematocrits to adequately oxygenate their tissues. Other symptoms that may be reported by anemic patients are palpitations, pounding in the ears, and vertigo.

Signs and symptoms vary with individual uremic patients, and some may undergo dialysis for several months without requiring blood transfusions. Others may arrive at chronic hemodialysis severely anemic and require frequent transfusions just to maintain adequate hematocrits. Again, the presence or absence of kidney tissue may have an important role to play and it is generally accepted that anephric patients will have consistently low hematocrits.


The prime objective in treating uremic anemia is the alleviation of anoxic symptoms, and this is best done through periodic transfusions of fresh blood cells. There are many dangers inherent in blood transfusions, however, and these must be weighed carefully when considering treatment.

Unit screening techniques are perfected and commonly employed, every unit of donor blood carries the risk of being contaminated with the hepatitis virus. The seriousness of serum hepatitis may be accentuated in a uremic patient whose general condition is poor and whose resistance to infection is low. On the other hand, there have been cases of essentially asymptomatic hepatitis, which produces the danger of unsuspected contamination of staff and other patients.

A second danger is the possibility of a reaction caused by carelessness in crossmatching or administering donor blood, or by impurities in the blood itself. Patients whose fluid balance is not well controlled run the risk of circulatory overload when 350 ml to 1,000 ml of donor blood are administered. Isosensitization to red and white cell antigens can produce circulating antibodies, which may cause acute or hyperacute rejection of a transplanted organ. Frequent transfusions carry a possible risk of overloading the recipient with iron.

Prevention of the need for transfusions is thus vital. Adequate nutrition may help in maintaining the hematocrit level, and sufficient protein, iron, and vitamins (especially B6, B12, and C) should be included in the diet. Because folic acid is water soluble and not bound to protein, substantial amounts may be lost during dialysis. Multivitamin supplements are frequently given to uremic patients. Excessive blood loss may be avoided by decreasing the frequency of lab tests and by care in handling the dialyzer and in returning the blood to the patient after dialysis. Properly occluded roller pumps and avoidance of turbulence in the extracorporeal circuit will minimize hemolysis. Prompt treatment of excessive or chronic bleeding, especially from the G.I. or G.U. tracts, is essential, and occasionally surgery is required; for example, hysterectomy, gastrectomy, removal of polycystic kidneys, etc.

Patients who have developed iron deficiency, manifested by microcytic, hypochromic red cells, decreased transferrin saturation, and absent bone marrow iron, usually respond to oral or parenteral iron administration (Richardson & Weinstein, 1970).

Androgenic hormones have been shown to stimulate production of erythropoietin. Some centres have recently been attempting to treat uremic anemia with frequent administration of large doses of testosterone preparations. Richardson and Weinstein of Miami reported erythropoietin stimulation in adequately dialyzed renal failure patients. This was demonstrated by a rise in arterial hematocrit, red cell volume, red cell volume per kilogram of body weight, shortened plasma iron clearance and, in some patients, increased iron turnover and utilization. Fifteen male patients were given courses of testosterone enanthate, 400 mg to 600 mg, IM weekly, for five to 44 weeks. On the basis of their experience and observations, the authors felt that when blood loss was minimized, transfusions for adequately dialyzed, well-nourished patients should rarely be required. The authors anticipated that their record of 46 transfusions for 264 patient months (0.17 transfusions per patient month) would be improved with further treatment.


Due to lack of renal erythropoietin production, the essentially normal bone marrow is incapable of undergoing a compensatory erythroid hyperplasia to counteract such hematologic side effects of uremia as excessive blood loss, hemolysis, and shortened red cell life span. The result is the characteristic anemia of renal failure. Symptoms develop gradually with the progression of the disease (presumably as more erythropoietin--producing cells are destroyed) and include weakness, fatigue, and pallor. The most obvious treatment is restoration of red cell volume by transfusions of fresh blood, but this carries with it such risks as serum hepatitis, transfusion reactions, antibody formation, and circulatory overload. Prevention of blood loss during dialysis or systemically, adequate nutrition, and prevention of red cell damage from dialysis equipment are all vital factors in diminishing anemia. Experiments have shown androgenic hormones to be effective in stimulating production of erythropoietin, possibly in extra-renal centres.

About the author

Christine Frye was an active member of CANSECT as early as 1969 and held different positions on the Board of Directors as well as writing articles for the journals.


Adamson, J.W., Eschbach, J., & Finch, C.A. (1968). The kidney and erthropoiesis. Amer. Jour. Med., 725f.

Brest, A.N., & Moyer, J.H. (Ed.). (1967). Renal Failure. Toronto: J.B. Lippincott and Co.

Bright, R. (1836). Cases and observations illustrative of renal disease accompanied with the secretion of albuminous urine. Guy's Hospital Report, 1, 340.

Hampers, C.L., & Schupak, E. (1967). Long-term hemodialysis (p. 98). New York: Grune and Stratton.

Richardson, J.R., & Weinstein, M.B. (1970). Erthropoietin response of dialyzed patients to testosterone administration. Ann. Int. Med., 73, 403-407.

Schreiner, G.E., & Maher, J.F. (1961) Uremia: Biochemistry, pathogenesis, and treatment. Springfield, Il: C.C. Thomas.

Schreiner and Maher, op. cit.

By Christine Frye, RN, CP, Dialysis Unit, Ottawa Civic Hospital
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Article Details
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Title Annotation:1970s
Author:Frye, Christine
Publication:CANNT Journal
Article Type:Disease/Disorder overview
Geographic Code:1CANA
Date:Jul 1, 2008
Previous Article:Remembering the past: peritoneal dialysis practices.
Next Article:Memories of a retired dialysis technologist (1974-2004).

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