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.
BEFORE STARTING ERYTHROPOIETIN THERAPY
Before starting a patient on erythropoietin therapy, it is important to reverse any other contributory causes to the anemia. The most important cause includes iron deficiency; iron deficiency in doubt should be treated with a trial of IV iron. Blood loss that should be corrected by transfusion of packed red blood cells, and underlying infection or inflammatory disease; difficult to diagnose, but a raised CRP level may be indicative.
Screening for hyperparathyroidism, aluminum toxicity, vitamin B12 and folate deficiency, hemolysis, or an underlying hemoglobinopathy should be performed if relevant. If abnormalities in the red cell indices or blood film are indicated, then a bone marrow sample should be undertaken to detect such conditions as myelodysplasia.
If the serum ferritin is less than 100 µg/L, one or more top-up infusions of IV iron is done since the demands for iron after erythropoietin is started will be great, and without iron supplementation, the patient will almost certainly have a suboptimal response.
STARTING THE PATIENT ON ERYTHROPOIETIN
The optimal dose for treating renal anemia is around 2000 units of recombinant human erythropoietin twice or thrice weekly, given subcutaneously. This is appropriate for both hemodialysis and peritoneal dialysis patients, although in certain instances the IV route may be used for hemodialysis patients; in patients with a needle phobia or those demonstrating poor compliance.
Scientists argued that the SC route results in lower dose requirements compared with IV administration. Some studies, however, have shown no difference in dose requirements between IV and SC administration, but no study has suggested lower doses with the IV route. There is no longer any indication for doses to be calculated per body weight, because such ‘‘fine-tuning’’ of erythropoiesis is not required, and this can potentially result in wastage of incompletely used vials.
Dosage requirements are same for both hemodialysis and peritoneal dialysis patients but some argued that hemodialysis patients are slightly more resistant to the effects of erythropoietin than peritoneal dialysis patients, and hence dosage requirements are to be higher.
With subcutaneous administration, it is possible to give erythropoietin once weekly using doses such as 4,000 or 10,000 units, but the total dosage requirements are likely to be greater than if the drug is administered as split doses two or three times a week. Once-weekly administration of intravenous erythropoietin is, however, not recommended, since the serum elimination half-life with this route is only around 8 hours.
Before initiating erythropoietin the patient must have adequate iron stores, Serum ferritin must be >200µg/L and transferrin saturation >20%.
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TITRATING DOSE OF ERYTHROPOIETIN
- Target hemoglobin should be achieved within 3-4 months of erythropoietin therapy.
- During the maintenance phase, many patients require erythropoietin of 6000 – 9000 IU/week, but this should be managed individually.
- If hemoglobin rises too fast, temporarily withhold erythropoietin therapy. If hemoglobin falls about 1g/dl per month, reinstate erythropoietin therapy at a dose approximately 25% below the previous dose.
- Decrease dose by between 25 – 50% if hemoglobin increases more than 2.5 g/dl in a month.
- Increase dose of erythropoietin by 25% if an increase in hemoglobin <1 g/dl over a month and adequate iron stores are maintained.
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