Friday, April 19, 2013

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Anemia in diabetic patients - Erythropoietin treatment?

If you encounter a normochromic and normocytic anemia in a diabetic patient, do not forget that it may be a case of erythropoietin deficiency. This deficiency can occur early in diabetic nephropathy (well before stage 5 of chronic kidney disease).

In adults, about 85-90% of the erythropoietin comes from the kidneys and 10-15% from the liver. It is produced by interstitial cells in the peritubular capillary bed of the kidneys and by perivenous hepatocytes in the liver. In cases of decreased renal mass, the level of erythropoietin falls and does not increase much in response to hypoxia (anemia). This occurs even if the liver is normal as the latter cannot compensate for the kidney's loss of function.

Since the availability of recombinant human erythropoietin to patients in 1989, anemia and transfusion requirements have become relatively  rare in patients on hemodialysis.
After adequate treatment with erythropoietin, studies have demonstrated that there is an:
1) enhanced exercise capability, presumably partly because of improved cardiac function with reduction in ventricular hypertrophy,
2) improved quality of life with improved physical performance, work capacity and cognitive capacity,
3) improved sexual function,
4) reduced rates of hepatitis and iron overload because of fewer transfusions.

All of the erythropoietin preparations are now referred to collectively as erythropoiesis stimulating-agents (ESAs). So far, intravenous route has been the sole route of administration and is given during hemodialysis but investigations are going on about the possibility of subcutaneous administrations.

With subcutaneous administration, peak serum concentrations of about 4% to 10% of an equivalent IV dose are obtained at around 12 hours, and thereafter they decay slowly such that concentrations greater than baseline are still present at 4 days.
The bioavailability of subcutaneous epoetin is around 20% to 25%. Nevertheless, subcutaneous application
is more efficient than IV application, allowing an approximately 30% dose reduction to maintain the same hemoglobin concentration.
Presumably, the early peak concentrations of epoetin after IV injection are inefficient, but the more prolonged elevation of hormone concentrations after subcutaneous application allows a more sustained stimulation of red cells production. Thrice-weekly administration has remained the most popular dosage frequency for both IV and subcutaneous administration, although once-weekly, twice-weekly and
seven-times-weekly (once-daily) dosing have all been used.

The hemoglobin target should be in the range of 11-12 g/dL and should not be greater than 13 g/dL.

Above is a diagram showing the change in hemoglobin level (blue line) with respect to different dosage of erythropoietin from 1991 till 2009 in an attempt to keep the hemoglobin in the target range. Hemoglobin level should be tested at least once monthly. 


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