Management of Anemia in Chronic Kidney Disease (CKD)

There are two important reasons to correct anemia in renal failure patients. One is to improve or reverse the symptoms associated with renal anemia, and the second is to seize or reverse the deleterious effect of long-standing anemia on the heart and other organs which lead to improved cardiovascular morbidity and mortality in dialysis patients.

Click here to know more about Anemia in CKD.

Management of anemia in renal failure has been advanced after the introduction of recombinant human erythropoietin. Some of the other factors that help in the management of anemia are mentioned below.

HEMANATIC SUPPLEMENTS

Patients with chronic renal failure are more likely to develop deficiencies of vitamins and minerals necessary for red cell production, particularly iron, vitamin B12 and folate deficiency as a result of diet restrictions, poor appetite, increased dialyzer and gastrointestinal blood loss.

Hemodialysis patients on average have blood loses up to 4-5mg per day and folate loses are seen in the majority of the hemodialysis patients. Blood levels of iron, vitamin B12, folate has to be measured regularly and deficiencies have to be treated and supplements are given as required.

DIALYSIS

Dialysis itself helps in the management of anemia as spontaneous improvement of anemia is seen in hemodialysis patients during early days after starting hemodialysis, may be due to enhanced red cell survival. Major improvement in hemoglobin is seen in CAPD (Continuous Ambulatory Peritoneal Dialysis) than with Hemodialysis, but after few years down the line, little difference is seen between two modalities.

Research studies showed that underdialysis may resist erythropoietin therapy and increasing dialysis prescription may itself cause an improvement in hemoglobin concentration in hemodialysis patients receiving erythropoietin. Click here to know about “Development of Anemia in Chronic Hemodialysis Patients”.

ANDROGEN THERAPY

Historically Androgens are used to treat anemia in dialysis patients. Androgens increase erythropoiesis by stimulating endogenous erythropoietin production, either from residual renal tissue or from the liver. Androgens also help to increase the sensitivity of erythroid precursor cells to erythropoietin.

But high incidence of side effects is seen with the use of androgens, such as virilization, muscle and liver damage and cholestasis.

BLOOD TRANSFUSION

Before the introduction of erythropoietin therapy repeated blood transfusions are done to correct anemia in renal failure. Blood transfusion had lots of disadvantages;

• Frequent blood transfusion suppresses residual endogenous erythropoietin production and erythroid activity.
• Repeated blood transfusion cause iron overload and iron accumulation in tissues, with long-term serious effects on the heart, liver, pancreas, and endocrine glands.
• Blood transfusion exposes the dialysis patient to the risk of infections such as hepatitis B and C, cytomegalovirus, and human immunodeficiency virus.
• Blood transfusion exposes the dialysis patient to a wide range of HLA antigens, resulting in cytotoxic antibody production, which renders successful renal transplantation less likely by reducing the chances of obtaining a negative cross-match and increasing the risk of acute rejection episodes.

INTRAVENOUS IRON

Studies showed that aggressive iron supplementation for anemia in renal failure rarely produced a complete correction of anemia but raise of 1-2 g/dL of hemoglobin is seen even in iron-replete patients. After the introduction of erythropoietin, IV iron is used to enhance the response to erythropoietin. Intravenous iron should be withheld when serum ferritin >800 ng/ml.Intravenous iron should not be given when infection is present because of the theoretical risk that neutrophil function may be adversely affected. Macrocytosis developing during iron supplementation may reflect the development of folate deficiency.

Adverse effects of Intravenous iron include; hypotension, nausea, vomiting, sweating, back pain, pruritis and a sudden feeling of being unwell.

Intravenous Iron Preparations:

Three preparations of Intravenous irons are available; iron sucrose/iron III hydroxide sucrose complex (Iron Saccharate), Sodium ferric gluconate and iron dextran.

Iron Sucrose:

Widely used and efficacious with a low incidence of adverse reaction. No need for test dose before first administration.

• Dosing: 100mg at the end of hemodialysis on 10 successive dialysis sessions if serum ferritin is<200 ng/ml. Later 100mg weekly once at end of hemodialysis while serum ferritin <600 ng/ml. 200mg of iron sucrose can be given once in 1 – 3 months in peritoneal dialysis and pre-dialysis patients as an Intravenous Infusion.
• Can be given slow intravenous injection at 20 mg/min or as an intravenous infusion.
• Administration Protocols: 100 – 200 mg undiluted over 5 – 10 min 20 mg/min is recommended.100 mg undiluted over 2 min reported to be safe, 100 mg in 100 ml of normal saline over 15 min.
• Changes in transferrin saturation and ferritin levels can be measured 48 hrs after intravenous administration.

Sodium Ferric Gluconate ( Ferrlecit)

• Non-dialysable and no need for test dose before initial administration.
• Common mild reactions
• Usually given as 60 – 125 mg of Intravenous infusion undiluted over 5 – 10 min (12.5 mg/min) during consecutive dialysis session until 1 g is administered. Later 125 mg weekly while serum ferritin <600 ng/ml.
• Larger doses can be given in peritoneal and pre-dialysis patients; 300mg once in 3 months over 90 min to prevent frequent hospitalization or 125 mg in 100 ml normal saline over 60 min.

Iron dextran

• Risk of anaphylactic reactions is more
• Can lead to the generation of antidextran antibodies
• A test dose of 20 mg diluted in 50 ml saline over 30 min, because of the risk of anaphylaxis.
• Other adverse effects include itching, dyspnoea, and wheezing, arthralgia, myalgia, fever, headache.
• Usually 20 – 100 mg for 10 – 20 hemodialysis sessions done to initially treat iron deficiency, later 50- 100 mg intermittently usually weekly, fortnightly or monthly to maintain iron stores. Alternatively, 250 mg over half an hour once in a month given at the end of dialysis bt slow injection or infusion.
• In CAPD or predialysis patients, 500 mg can be diluted into 250 ml saline and given over 30 – 60 min.
• Less used because of wide adverse reactions.

ERYTHROPOIETIN THERAPY

Erythropoietin therapy is one of the greatest inventions in Nephrology and it changed the way we treat anemic patients, which we were only dependent on blood transfusions in the past. Erythropoietin is a 165 amino acid secreted glycoprotein. Recombinant erythropoietin is available in two forms α-epoetin and β-epoetin and Darbepoetin is a longer acting erythropoietin with the half-life approximately three folds longer than recombinant erythropoietin. 1µg darbepoetin is equal to 200 IU OF erythropoietin.This has been achieved by adding two extra N – linked carbohydrate side – chains to the erythropoietin molecule. As a result, darbepoetin requires less frequent dosage, usually once a week or once in every two weeks and sometimes only once a month in stable hemodialysis patients.