Restless legs syndrome (RLS) affects patients on chronic hemodialysis with about 4 times the prevalence of that seen in the general population. An Italian research group presented their findings here at the XLVII European Renal Association-European Dialysis and Transplant Association Congress, which showed an association between RLS and levels of C-reactive protein (CRP) in chronic hemodialysis patients.

RLS manifests as an urge to move the legs when at rest, thus disturbing the initiation and maintenance of sleep. Patients with RLS complain of insufficient and nonrestorative sleep, daytime sleepiness, and diminished functioning. The prevalence of anxiety and depression is also higher among people with RLS.

The primary form of RLS affects about 5% of the general population. From their study of 58 chronic hemodialysis patients, lead investigator Giulio Romano, MD, professor of nephrology at the University of Udine in Italy, found a prevalence of RLS of 21.4%. RLS patients were defined as those who experienced symptoms at least 2 times a week.

When chronic hemodialysis patients with RLS (n = 12) were compared with those without RLS (n = 46), the RLS patients reported significantly longer sleep latency (time to fall asleep), less sleep time, longer naps, a higher prevalence of insomnia (P < .001 for all), and a higher prevalence of excessive daytime sleepiness (P < .05).

Dr. Romano told Medscape Medical News that among RLS patients undergoing chronic hemodialysis, “the interesting conclusion of our work is that there is a correlation between restless legs syndrome and an increase of inflammatory cytokines and the increase of CRP.” Total sleep time significantly negatively correlated with the level of serum CRP (r = .401; P < .004); the higher the CRP, the shorter the sleep time. The group of patients with RLS had serum CRP levels of 43.96 ± 23.71 mg/L, compared with 15.24 ± 3.94 mg/L for the non-RLS patients (P = .04).

Looking at a variety of other common laboratory parameters, the researchers found a significant difference between patients with and without RLS only for serum iron (47.27 ± 5.73 μg/dL vs 64.7 ± 4.92 μg/dL, respectively;P = .03) and percent transferrin saturation (20% ± 2.09% vs 25.74% ± 1.46%, respectively; P < .05). There were no significant differences between the groups with regard to hemoglobin, hematocrit, urea, creatinine, albumin, or parathyroid hormone levels; there was also no significant difference in Kt/V, indicating that underdialysis is not the cause of the RLS.

Dr. Romano noted that several studies have shown that increased inflammation is associated with elevated cardiovascular risk in patients on chronic hemodialysis. Also, he said there is evidence that sleep disorders induce elevated levels of proinflammatory cytokines.

“We think that if patients have some sleep disorders, they evoke inflammation,” he said; “if we treat the sleep disorders, we reduce a cardiovascular risk factor because CRP is a possible cause of increased cardiovascular risk.” The hemodialysis patients without RLS, he noted, had much lower CRP levels. Similarly, the levels of transferrin saturation, another marker of inflammation, were different between patients with and without RLS.

Dr. Romano said the next step is to work with his colleagues in the neurology department to treat the RLS patients with antiparkinson drugs to see if reducing nighttime leg movements and restoring sleep lowers CRP levels, and eventually, cardiovascular risk.

Nageswara Reddy, MD, assistant professor of nephrology at Manipal University in India, who was not involved with the study, told Medscape Medical News that it makes sense to him that RLS is associated with inflammatory markers. Cardiovascular mortality, which is the main cause of death among hemodialysis patients, is associated with elevated levels of CRP, but it might be associated with other underlying causes as well.

“We have to find out all risk factors. Maybe lack of sleep is another risk factor,” Dr. Reddy hypothesized, and suggested that other inflammatory markers, in addition to CRP, be investigated.