Restless-Legs-Syndrom bei dialysepflichtiger Niereninsuffizienz: Untersuchungen zur Pathophysiologie und Schlafqualität – spielt Homocystein eine Rolle?
Restless-Legs-Syndrome in patients with renal insufficiency on hemodialysis: examining pathophysiology and sleep quality- does homocystein play a role?
by Katrin Gade
Date of Examination:2012-07-09
Date of issue:2012-06-19
Advisor:PD Dr. Stefan Cohrs
Referee:PD Dr. Stefan Cohrs
Referee:Prof. Dr. Martin Sommer
Referee:Prof. Dr. Oliver Gross
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EnglishSleep disturbances are a common problem among patients with chronic renal insufficiency on hemodialysis and often have multiple causes. One is the high prevalence of the uremic form of restless legs syndrome (RLS). Associated symptoms, such as uncomfortable sensations in the legs, an urge to move and limb jerking, usually worsen in the evening, reducing the sleep quality of affected individuals. The etiology of uremic RLS still remains unclear; however, a neurotransmitter imbalance with a predominance of excitatory effects due to metabolic changes seems likely.Our research investigated whether an elevated plasma concentration of the amino acid homocysteine is associated with RLS occurrence in patients on hemodialysis. Total homocysteine plasma concentration is known to be elevated in many patients on dialysis, and the substance acts as an agonist at the N-Methyl-D-aspartic acid (NMDA) receptor. Therefore, it has excitatory properties and impairs the metabolism of dopamine, which is implicated in RLS. In this study, we took blood samples from 52 renal-insufficient patients on dialysis. Half of these patients suffered from uremic RLS (RLSpos, n = 26) while the other half did not (RLSneg, n = 26). Total plasma homocysteine concentrations (tHcy) were compared between the two groups. Furthermore, we analysed several other laboratory parameters which have previously been associated with RLS in uremic as well as in non-uremic patients (creatinine, urea, vitamin B12, folic acid, parathormone, hemoglobin, iron, ferritin, phosphate, calcium, magnesium, and albumin). Additionally, we compared subjective sleep quality between RLSpos and RLSneg patients using the Pittsburgh-Sleep-Quality-Index-Questionnaire and investigated a possible relationship between laboratory parameters and sleep quality. Taking individual albumin concentrations into account, a significant positive correlation between tHcy and RLS occurrence was observed in our study (r= 0.246; p=0.045). All other laboratory parameters did not differ significantly between the RLSpos and RLSneg patients. Irrespective of group membership, bad sleep quality was associated with higher concentrations of serum parathormone (p=0.028). Sleep quality was significantly more reduced in RLSpos compared to RLSneg patients (p=0.003). RLS severity correlated with impaired sleep quality (r= 0.510; p=0.004).Our results confirm that uremic RLS is a major cause of sleep impairment among patients on hemodialysis. Subjective sleep quality appears to deteriorate with increasing severity of RLS. Elevated levels of total plasma homocysteine may indeed play an etiologic role in uremic RLS. Furthermore, it appears that bad sleep quality in RLS-affected as well as in non-RLS affected patients on hemodialysis is associated with higher parathormone levels. Further investigations need to be carried out to verify these relations.
Keywords: Renal insufficiency; dialysis; restless legs; homocysteine; parathormone; sleep quality; laboratory parameters
Schlafstörungen sind bei chronisch niereninsuffizienten Hämodialysepatienten ein bekanntes Problem und haben oft multiple Ursachen. Ein wesentlicher Faktor ist hierbei die hohe Prävalenz der urämischen Form eines Restless-Legs-Syndroms (RLS) bei dieser Patientenklientel. Durch die vor allem in den Abendstunden auftretenden RLS-typischen Beschwerden wie sensible Missempfindungen, imperativen Bewegungsdrang der meist unteren Extremitäten und unwillkürliche myoklonieähnliche Bewegungen ist die Schlafqualität der Betroffenen deutlich beeinträchtigt. Die
Schlagwörter: Niereninsuffizienz; Dialyse; Restless Legs; Homocystein; Parathormon; Schlafqualität; Laborparameter