What Can Cistanche Do To Anemia Of Chronic Kidney Disease?

Anemia of Chronic Kidney Disease

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Keywords: chronic kidney disease, anemia, erythropoietin, kidney

Background

Anemia is a well-known and major complication of chronic kidney disease and is considered a hallmark of chronicity of renal disease 1 . Anemia is predominantly due to decreased production of erythropoietin by the diseased kidney resulting in reduced production of red cells from the erythroid marrow. Erythropoietin is predominantly produced by peritubular cells in the kidney and is the hormone responsible for maintaining the proliferation and differentiation of erythroid progenitor cells in the bone marrow. Loss of peritubular cells lead to an inappropriately low level of circulating erythropoietin in the face of anemia. Besides this, several other factors may contribute to the development of anemia in patients with chronic kidney disease (Table 1).

In addition to erythropoietin deficiency in chronic kidney disease, iron deficiency is common in patients of chronic kidney disease, and 23-37.5% of patients are deficient in iron and it is a major contributing factor for anemia in these patients. The severity of anemia depends upon the severity of the chronic renal failure. Anemia is responsible for many signs and symptoms observed in chronic kidney disease. It causes marked fatigue and reduced exercise tolerance. Anemia results in left ventricular hypertrophy, angina, and heart failure 2. It also causes an impaired immune response, decreased cognitive function, mental ability, and disturbed sleep 3. In addition, anemia may play a role in growth retardation in pediatric patients.

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Effects of Correction of Anemia

Improvement in anemia results in improved quality of life, maximal exercise capacity, cognitive function, sleep pattern, nutritional status, improvement of sexual function, and immune response (Table 2). It also causes a reduction in left ventricular hypertrophy.

Evaluation for Anemia

The current recommendation as defined by anemia working group 4 (National Kidney Foundation-DOL) for target hematocrit/hemoglobin in chronic renal failure patients are hematocrit between 33-36% and hemoglobin between 11-12 gm/dl with appropriate therapy. The availability of recombinant human erythropoietin (rhu erythropoietin) has revolutionized the management of anemia in chronic renal failure. Evaluation of anemia of CRF should be initiated when Hct is <33% (hemoglobin <11 g/dl) in pre-menopausal females and prepubertal males and Hct is <37% (hemoglobin <12 g/dl) in postmenopausal females and adult males.

Management of Anemia in CRF

The management strategies for anemia of CRF include:

1. Erythropoiesis stimulating agents

2. Iron status management

3. Miscellaneous drug therapy

Erythropoietin Therapy

The availability of recombinant human erythropoietin (rHu erythropoietin) in 1985 was a significant advance in the management of anemia. It is given by subcutaneous route, in the dose of 80-150 IU/kg per week in two to three divided doses. The main advantage of s.c. erythropoietin over i.v. erythropoietin is that for attaining a similar rise of Hct, the dose requirement is 20 to 40% lower. The response to treatment is seen by a rise in Hct. If the rise of the Hct is by 1% over the first week or more than 8% over 2 weeks after starting erythropoietin dose, it indicates a good response. erythropoietin should be continued till target Hct is achieved. Monitor the Hct every 4 weekly thereafter. Alternatively, Darbepoietin-α can be used in place of rHu erythropoietin which has a longer half-life and is administered less frequently. It is as effective as erythropoietin in maintaining hemoglobin levels. In addition, it assures better compliance, though it is much more expensive. It is not yet available in India. Many patients achieve target hemoglobin but some patients do not achieve satisfactory responses to erythropoietin.

The causes of hyporesponsiveness are listed in Table 3. Some patients need adjustment of anti-hypertensive medication as erythropoietin causes an increase in blood pressure.

Iron Therapy

The initiation of erythropoietin therapy by increasing erythropoiesis increases the demand for iron and iron deficiency results because it cannot be met by body iron stores or sometimes even after oral iron supplementation. Iron deficiency can be functional or absolute iron deficiency. Functional iron deficiency can be defined as serum ferritin level >100 µg/l and transferrin saturation <20%. On the other hand, absolute iron deficiency can be defined as serum ferritin level <100 µg/l and transferrin saturation <20%.

Disturbances in iron homeostasis in chronic kidney disease can be due to some causes as shown in Table 4 and the diagnosis of iron deficiency in a patient with chronic kidney disease can be assessed by various indicators of iron status (Table 5).

Treatment of iron deficiency in patients of chronic kidney disease

Iron therapy could be given as oral iron preparation or as intravenous iron supplements. Patients who do not tolerate oral iron therapy need parenteral therapy. The treatment is given till the patient achieves the target hemoglobin level. Parenteral iron therapy is necessary for patients of chronic kidney disease on maintenance hemodialysis. Intravenous iron is now known to be better than oral iron in replenishing body iron stores. With intravenous iron, greater hematocrit can be achieved as compared to oral iron and the dose of erythropoietin can be decreased. The usual adult dose is 100 mg intravenously 1-3 times/week to a total dose of 1000 mg in 10 doses. It can be repeated if needed. Slow IV injection into dialysis line at a rate of 1 ml undiluted solution per minute not exceeding 100 mg iron/injection can be given. Iron can also be given as drip infusion for hemodialysis patients by diluting in 100 ml 0.9% NaCl. The diluted solution should be infused at a rate of 100 mg of iron over at least 15 minutes. The maintenance dose is 50 to 100 mg every 1 to 2 weeks. Various types of parenteral iron preparations are available such as iron dextran, iron sucrose, and sodium ferric gluconate.

Monitoring of the patients of anemia in chronic kidney disease during therapy

In people with anemia of chronic kidney disease, hemoglobin and Hct should be monitored every 2–4 weeks during the initial phase and every 1–3 months subsequently. Besides this, periodic evaluation of iron indices should be done.

Miscellaneous Treatment

Some patients do not respond to erythropoietin and iron therapy. Various factors responsible for this hyporesponsiveness to erythropoietin or Iron therapy have been listed in Table 3. Efforts should be made to correct the underlying defect. Sometimes, these patients may benefit from treatment with various adjuvants which include androgen, folic acid, L-carnitine ascorbic acid, vitamin D, Vitamin B 6. If the patient continues to be anemic, a blood transfusion may be required.

a. Androgens may be prescribed for anemic patients who cannot afford erythropoietin. Nandrolone decanoate is usually preferred. Prolonged therapy with this agent may be associated with various side effects, thus limiting its use.

b. L-carnitine: Used in patients who were hypo-responsive to erythropoietin in the dose of 1-3 mg/kg intravenously. Vesela et al (2001) in their recent study reported a decrease in erythropoietin dose by 37% in patients receiving L-carnitine 1 gm IV post-hemodialysis; during the same time hematocrit increased from 27 to 33%.

c. Others: Ascorbic acid 300-500 mg/day is used for patients of hemodialysis. Vitamin E helps reduce erythropoietin doses. Zinc supplementation may be useful in malnourished patients. Growth hormone has been found to stimulate erythropoiesis.

d. Role of blood transfusions: In some patients, there is a role of blood transfusion. These are severely anemic patients with hemoglobin less than 5g/dl and hyporesponsive to erythropoietin therapy with chronic blood loss.

SUMMARY

Anemia is a universal feature in patients with chronic kidney disease and contributes significantly to morbidity and mortality in these patients. Anemia increases with the severity of chronic kidney disease. A large number of Indian patients are already iron deficient before developing chronic kidney disease. With the availability of rHu erythropoietin, a large number of patients with chronic kidney disease with anemia can be benefitted. rHu erythropoietin and Iron replacement therapy are the mainstays of the treatment of anemia of chronic kidney disease. Correction of anemia in chronic kidney disease significantly improves the quality of life and decreases cardiovascular morbidity and mortality.

REFERENCE

The source is from Medicine Update.