Restless Legs Syndrome in Advanced Renal Disease
Abstract & Commentary
By Alexander Shtilbans, MD, PhD
Assistant Professor of Neurology, Weill Cornell Medical College
Dr. Shtilbans reports no financial relationships relevant to this field of study.
Synopsis: Restless legs syndrome is prevalent in Taiwanese dialysis patients and is associated with type 2 diabetes, anemia, lower serum iron, and long duration of dialysis.
Source: Lin CH, et al. Restless legs syndrome in end-stage renal disease: A multicenter study in Taiwan. Eur J Neurol 2013;20:1025-1031.
Restless legs syndrome (rls) is a sensorimotor disor-der characterized by a distressing urge to move the legs, occasionally the arms, and is usually accompanied by uncomfortable sensations of pain in the affected body parts, mostly the legs. The sensations occur particularly in the evening or at night and are relieved by movements. RLS can be primary or secondary due to metabolic abnormalities. The pathophysiology of primary RLS is still poorly understood, but is thought to be related, at least in part, to dysfunction of the central dopaminergic system, iron metabolism, and/or central opioid neurotransmission. Secondary RLS is classically associated with iron deficiency anemia, pregnancy, or uremia in end-stage renal disease. The overall prevalence of RLS in the European and North American population is believed to be about 5%. While the prevalence of the primary RLS in Asian countries is less, secondary RLS, such as related to end-stage renal disease (ESRD), is more common in those populations.
The authors of this paper conducted a multicenter, case-control study aimed to investigate the prevalence of RLS in dialysis patients in Taiwan, a country with a high incidence of uremia, to study associated risk factors for RLS. They recruited 1130 patients with ESRD from 17 dialysis centers. Demographic data were collected, and evaluations by a nephrologist and a movement disorder neurologist were performed with a detailed questionnaire and clinical examination, followed by collection of blood samples. In cases where distal polyneuropathy was suspected, nerve conduction studies were performed.
They found that 286 patients (25.3%) had RLS, and those patients were more likely to have lower serum iron, type 2 diabetes, and neuropathy compared to patients without RLS. Nerve conduction studies confirmed polyneuropathy in 86 out of the 303 subjects suspected to have it. No other demographic factors or other comorbidities were found to correlate with the prevalence of RLS. Patients with RLS had prolonged sleep-onset latency as a consequence of their RLS. A multivariate logistic regression analysis showed that a history of type 2 diabetes was significantly correlated with moderate to severe RLS (odds ratio [OR] = 4.04). Low hemoglobin level (OR = 5.41) and duration of dialysis (OR = 1.01) also showed significant correlations with the severity of RLS.
The prevalence of RLS in patients with end-stage renal disease varies widely in published series from 6-70%. The authors of this case-control study evaluated the prevalence and risk factors for RLS among dialysis patients in Taiwan. Besides establishing the prevalence of RLS in this population to be 25%, the authors found a high correlation with type 2 diabetes, low hemoglobin, and duration of dialysis. The authors propose that the great variation in prevalence of RLS in dialysis patients in different countries may be due to either genetic predisposition and/or differences in strategies for managing dialysis patients, and it is unclear whether RLS is associated with the dialysis procedure itself, or related, at least in part, to the advanced renal disease. The authors argue that the associated presence of diabetic neuropathy could be responsible for the increased prevalence of RLS in patients with type 2 diabetes, and the study might have underestimated the prevalence of peripheral neuropathy, since this diagnosis was only made upon confirmation with nerve conduction studies. A small fiber neuropathy may not be detected by nerve conduction studies and a skin biopsy is usually needed for the diagnosis. The authors further propose that there might be a decrease in central nervous system dopamine in patients with diabetes, which in turn could decrease central inhibition of the sensory input into the spinal cord, causing RLS symptoms. While these might be related, we know that not all Parkinson's disease patients, who clearly have dopamine deficiency, have RLS. A prospective cohort study of patients with mild-moderate renal disease would be useful to estimate at which point of their renal disease progression patients develop RLS and how much is related to dialysis.
