DYSREGULATION OF MELATONIN METABOLISM IN CHRONIC RENAL-INSUFFICIENCY - ROLE OF ERYTHROPOIETIN-DEFICIENCY ANEMIA

Chronic renal failure (CRF) is associated with a variety of neurologic al and endocrine disorders. Tn this study, we examined the effect of C RF 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 e rythropoietin-treated CRF animals (CRF/EPO, N = 6) was included to dis cern the possible role of EPO-deficiency anemia. Compared with the nor mal control group, the CRF group showed a marked attenuation of the no cturnal surge in serum melatonin concentration. In addition, pineal gl and melatonin content measured after a 12-hour dark cycle (less than o r equal to 2 lux) was significantly depressed in the CRI: group when c ompared to that obtained in the control group. However, the CRF animal s exhibited appropriate suppression of serum concentration and pineal tissue melatonin content in response to bright light (greater than or equal to 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 melat onin concentration. Regular EPO administration results in the correcti on of anemia and substantial reversal of this abnormality suggesting t he partial role of EPO deficiency. The possible role of melatonin dysr egulation in the pathophysiology of CRF and the potential value of mel atonin supplementation in this condition is uncertain and awaits futur e investigations.