Circadian sleep–wake rhythm disturbances in end-stage renal disease


End-stage renal disease (ESRD) is an increasing health problem worldwide. Given the increasing prevalence of this disease, the high cost of hemodialysis treatment and the burden of hemodialysis on a patient's life, more research on improving the clinical outcomes and the quality of life of hemodialysis-treated patients is warranted. Sleep disturbances are much more prevalent in the dialysis population than in the general population. Several studies investigating the effect and importance of sleep problems on quality of life in dialysis patients revealed that sleep disturbances have a major influence on the vitality and general health of these patients. Sleep disturbances in this patient group are caused both by the pathology of the renal disease and by the dialysis treatment itself. This Review focuses on circadian sleep–wake rhythm disturbances in individuals with ESRD. The possible external and internal influences on sleep–wake rhythmicity in patients with ESRD, such as the effect of dialysis, medications, melatonin and biochemical parameters, are presented. In addition, possible approaches for strengthening the synchronization of the circadian sleep–wake rhythm, such as nocturnal hemodialysis, exogenous melatonin, dialyzate temperature, exogenous erythropoietin, use of bright light and exercise during dialysis treatment, are explored. Further research in this area is warranted, and a greater awareness of sleep problems is needed to improve the quality of life of patients with ESRD.

Key Points

  • Sleep disturbances are much more prevalent in patients with end-stage renal disease (ESRD) than in the general population

  • Several studies on the impact and importance of sleep problems on quality of life in patients on dialysis revealed that sleep disturbances have a major effect on the vitality and general health of these patients

  • Sleep disturbances in patients on dialysis might be caused by the pathology of the renal disease as well as by the dialysis treatment itself

  • External and internal factors that might be associated with disrupted sleep–wake rhythmicity in patients with ESRD include dialysis, medications, melatonin rhythm and biochemical parameters

  • Approaches that might be useful in treating disturbances in the circadian sleep–wake rhythm in patients with ESRD include nocturnal dialysis, exogenous melatonin, lowering dialyzate temperature, exogenous erythropoietin, bright light and intradialytic exercise

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Figure 1: The human circadian clock.
Figure 2: Factors influencing the sleep–wake cycle.
Figure 3: Synthesis of melatonin from tryptophan.
Figure 4: The mechanism through which light inhibits melatonin secretion by the pineal gland involving the neural pathway originating in the retina and passing through the suprachiasmatic nucleus in the brain, to reach pinealocytes via adrenergic nerves and adrenergic receptors, and subsequently to the periphery.


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The authors would like to thank the Dutch Kidney Foundation for supporting our work and Inzicht Graphic Design, Arnhem, The Netherlands, for their assistance with the figures.

Charles P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the MedscapeCME-accredited continuing medical education activity associated with this article.

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Correspondence to Birgit C. P. Koch.

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Koch, B., Nagtegaal, J., Kerkhof, G. et al. Circadian sleep–wake rhythm disturbances in end-stage renal disease. Nat Rev Nephrol 5, 407–416 (2009).

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