Dysregulation of melatonin metabolism in chronic renal insufficiency: Role of erythropoietin-deficiency anemia

Abstract

Chronic renal failure (CRF) is associated with a variety of neurological and endocrine disorders. In this study, we examined the effect of CRF and the associated anemia on circadian variation of pineal hormone, melatonin. Animals were studied six weeks after 5/6 nephrectomy (CRF group, N = 26) or sham operation (control group, N = 28). A group of erythropoietin-treated CRF animals (CRF/EPO, N = 6) was included to discern the possible role of EPO-deficiency anemia. Compared with the normal control group, the CRF group showed a marked attenuation of the nocturnal surge in serum melatonin concentration. In addition, pineal gland melatonin content measured after a 12-hour dark cycle (< or = 2 lux) was significantly depressed in the CRF group when compared to that obtained in the control group. However, the CRF animals exhibited appropriate suppression of serum concentration and pineal tissue melatonin content in response to bright light (> or = 2500 lux). Administration of EPO led to correction of the CRF anemia and a marked improvement of the defective nocturnal rhythm of serum melatonin. Based on our results, experimental CRF is associated with a marked attenuation of the normal nocturnal surge of serum melatonin concentration. Regular EPO administration results in the correction of anemia and substantial reversal of this abnormality suggesting the partial role of EPO deficiency. The possible role of melatonin dysregulation in the pathophysiology of CRF and the potential value of melatonin supplementation in this condition is uncertain and awaits future investigations.