Ascorbic Acid Administration in the Treatment of Anemia in Chronic Hemodialysed Patients

Effects of Ascorbic Acid Administration in the Treatment of Anemia in Chronic Hemodialysed Patients With Iron Overload

The administration of ascorbic acid seemed to increase the iron available for erythropoiesis, thus improving the anemia response to the treatment.

The investigators therefore aimed to evaluate the effects of intravenous ascorbic acid administration in hemodialysed patients with iron overload.

Renal anemia is a complex condition in which chronic inflammation, among other factors, can change the iron distribution by locking it in deposits, and also, iron metabolism parameters. Thus, is hard to separate the iron functional deficit from overload.

The ascorbic acid is a hydrosoluble vitamin capable of reduction and hydrolysis. As a reduction agent, the ascorbic acid supports the transformation of ferric iron to ferrous iron. For instance, the ascorbic acid can increase digestive absorption and taking over the iron without transferrin, helps iron release from ferritin and hemosiderin and delays ferritin conversion to hemosiderin; therefore, the administration of ascorbic acid can increase the quantity of iron available for erythropoiesis by realising it from the deposits.

Consequently, the antioxidant function of ascorbic acid can increase the red cells' lifetime, reducing the inflammation and improving erythropoietin response Following these premises, recent studies have examined the effect of administrating ascorbic acid to hemodialysed patients with erythropoiesis stimulating agents (ESA) hyporesponsiveness anemia and functional deficit or iron overload markers. The results of administering ascorbic acid revealed an increased level of hemoglobin and transferrin saturation (TSAT) combined with the decrease of ESA doses. The major limitations of these studies are the short amount of time for observation (<6months) and the limited number of participants which hampered neither the complete evaluation of the goals, nor the adverse effects of supplementary administration of vitamin C.

Until now, the Clinical practice guidelines of Kidney Disease do not recommend currently using of high doses of vitamin C, considering the risk of a high level of oxalemia and the limited information about the benefits. Considering this background, we intended to evaluate the benefits of intravenous administration of ascorbic acid in hemodialysed patients with iron balance markers suggestive for iron overload.

Inclusion Criteria:

• Age above 18 years old
• At least 6 months on hemodialysis at the time of randomization;
• Kt/V≥1.2;
• average of the last three serum ferritin levels > 500 ng/mL AND
• Average of the last three TSAT levels > 20% and increasing
• ERI in the 4th quartile of the group

Exclusion Criteria:

• Active bleeding or other cause of anemia
• Serum level of intact parathyroid hormone (iPTH)>800 pg/mL
• Actual neoplasia
• HIV, Hepatitis B or C infections
• Significant inflammation (CRP>12mg/L) or acute infection
• Venous central catheter
• Severe hepatic, cardiovascular, psychic disease or other severe comorbidities
• Moderate or severe malnutrition
• Blood transfusions in the 2 months prior to screening
• Pregnancy or breastfeeding
• Inclusion in another clinical trial in the past month