Clearance of melatonin and 6-sulfatoxymelatonin by hemodialysis in patients with end-stage renal disease

Patients with end-stage renal disease (ESRD) suffer from a number of relate d disorders. These include endocrine abnormalities, sleep disturbances, and depression. Melatonin is involved in the synchronization of exogenous zeit gebers with the endogenous rhythms, and it has effects on various psycholog ical factors. As the concentrations of melatonin and the effects of dialysi s have only occasionally been investigated in ESRD, we performed a study in volving 35 patients, measuring the serum concentrations of melatonin, and o f its major metabolite 6-sulfatoxymelatonin (aMT6s), before and after hemod ialysis. Serum samples taken during morning hours from a control group (n = 11) with intact kidneys served as controls. Patients were dialyzed for app roximately 4 hr between 07:00 and 13:00 hr (SI), between 13:00 and 20:00 hr (S2), or between 18:30 and 22:30 hr (S3). Mean melatonin concentrations be fore hemodialysis were highly elevated when compared with the controls (40. 6 vs. 6.7 pg/mL; P < 0.001). Although melatonin levels were decreased to 20 .3 pg/mL after dialysis, they were still well above the control levels. Lik ewise, aMT6s concentrations before dialysis were highly elevated in ESRD pa tients before dialysis when compared with controls (39.5 vs. 2.0 pg/mL; P < 0.001), and also decreased by dialysis to levels still well above control levels (25.3 pg/mL). Clearance efficacy was better for melatonin (48.9%) th an for aMT6s (36.6%; P < 0.05). In ESRD patients, a diurnal rhythm for mela tonin was observed (S1, 45.1 pg/mL; S2, 31.5 pg/mL; S3, 48.7 pg/mL; P < 0.0 5), indicating that the normal synthesis rhythm is maintained. None of the following secondary disorders were correlated with melatonin concentrations : insomnia, delayed sleep onset, night-time arousals, and restless-leg synd rome. The reason for this observation is probably the melatonin concentrati ons, which were so high that no sub-classification could be identified. It is concluded that in ESRD patients, hemodialysis is unable to decrease elev ated levels of melatonin and aMT6s to normal values. It is speculated that some of the secondary disorders in ESRD are caused by supraphysiological co ncentrations of melatonin.