Melatonin Improves Erythropoietin Hyporesponsiveness via Suppression of Inflammation.

Abstract

Inadequate response to Erythropoietin Stimulating Agents (ESA) despite using relatively larger doses regimen represents a potential risk factor of Cardiovascular (CV) related mortality in addition to health-care economic problems in anemic patients with Chronic Kidney Disease (CKD). Erythropoietin (EPO) hyporesponsiveness related to inflammation has been increased progressively. Melatonin is well known as a potent anti-inflammatory agent. Therefore, the current study was designed to evaluate whether melatonin could improve anemic patients response to EPO. This single controlled clinical study was carried out in 41 CKD patients with hemoglobin (Hb) levels less than 11g/dl divided randomly in a 1:1 ratio into 2 groups; treatment group who received 5mg melatonin plus their regular treatments and control group who received their regular treatments only. Hematological and iron status parameters include Hb level, serum iron (S. iron), Transferrin Saturation Ratio (TSAT) and serum ferritin (S. ferritin) in addition to inflammatory parameters that include tissue necrotic factor alfa (TNF-α), interleukin-1beta (IL-1β) and interleukin-6 (IL-6) determined before and after 12 weeks of treatment. Melatonin remarkably increases the Hb level with a significant increase in S. iron and TSAT compared to baseline. The elevation of S. iron and TSAT was significantly higher in the melatonin group. Additionally, all inflammatory markers estimated were reduced significantly by melatonin compared to base line and control group. The results of the current study showed that melatonin has an advantageous effect on improving EPO response in anemic patients with CKD.