[Frontiers in Bioscience 17, 2644-2656, June 1, 2012]

The role of melatonin treatment in chronic kidney disease

Marije Russcher1, Birgit Koch2, Elsbeth Nagtegaal1, Karien van der Putten3, Piet ter Wee4, Carlo Gaillard4,5

1Department of Hospital Pharmacy, Meander Medical Center, Amersfoort, The Netherlands, 2Department of Hospital Pharmacy, Erasmus Medical Center, Rotterdam, The Netherlands, 3Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands, 4Department of Nephrology, VU University Medical Center, Amsterdam, The Netherlands, 5Department of Internal Medicine, Meander Medical Center, Amersfoort, The Netherlands


1. Abstract
2. Introduction
3. Definitions of renal disease
4. Circadian rhythm disorders in CKD
4.1. Sleep disturbances in CKD
4.1.1. Effects of dialysis on the sleep/wake rhythm
4.1.2. Nocturnal melatonin levels in CKD patients
5. Restoring circadian rhythm disorders in renal disease
5.1. Use of exogenous melatonin to treat sleep disorders in CKD
5.2. Effect of timing of dialysis related to sleep disorders in CKD
5.3. The effect of melatonin on blood pressure rhythm in CKD
6. The effect of melatonin on oxidative stress in CKD
7. Inflammation in CKD in relation to circadian disturbances
8. Remaining questions and future research
9. References


The pineal hormone melatonin plays a major role in circadian sleep-wake rhythm. Patients with Chronic Kidney Disease (CKD), especially those who are on hemodialysis, frequently suffer from sleep disturbances. In this review an overview is given of the classification of stages of chronic kidney disease, followed by a presentation of the circadian rhythm disorders in renal disease involving sleep disturbances in relation to melatonin deficiency. The therapeutic benefit of melatonin treatment in sleep disorders related to chronic kidney disease including the controlled trials solving this topic, is described. Furthermore, the beneficial effect of melatonin on blood pressure alterations in CKD states and the protection of melatonin in oxidative stress and inflammation in renal disorders are explored. Finally a hypothetic model is described for the relation between circadian rhythm disorders and CKD.