Pharmacological and non-pharmacological treatments for restless legs syndrome in end-stage kidney disease: a systematic review and component network meta-analysis

Abstract

Background Restless legs syndrome (RLS) is common among patients with end stage kidney disease (ESKD) and is associated with poor outcomes. Several recently published studies had focused on pharmacological and nonpharmacological treatments of RLS, but an updated meta-analysis has not been conducted. Methods The study population was adult ESKD patients on dialysis with RLS. Randomized controlled trials were selected. The primary outcome was reduction in RLS severity. The secondary outcomes were improvement in sleep quality and treatment-related adverse events. Frequentist standard network meta-analysis and additive component network meta-analysis was performed. The evidence certainty was assessed using Confidence in NMA (CINeMA) framework. Results A total of 24 RCTs with 1,252 participants were enrolled and 14 interventions were compared. Cool dialysate produced the largest RLS severity score reduction (MD: 16.82, 95% CI: 10.635–23.02) and high level of confidence. Other potential non-pharmacologic interventions including intradialytic stretching exercise (MD: 12.00, 95% CI: 7.04–16.97) and aromatherapy massage (MD: 10.91, 95% CI: 6.96–14.85) but all with limited confidence of evidence. Among the pharmacological interventions, gabapentin was the most effective (MD: 8.95, 95% CI: 1.95–15.85), which also improved sleep quality (SMD: 2.00, 95% CI: 0.47–3.53). No statically significant adverse events were detected. Conclusions The NMA supports that cool dialysate is appropriate to apply to treat patients with ESKD and RLS. Gabapentin is most effective pharmacologic intervention which also might improve sleep quality. Further parallel RCTs with sufficient sample sizes are required to evaluate these potential interventions and long-term effects.

Practice recommendations for the role of physiotherapy in the management of sleep disorders: the 2022 Brazilian Sleep Association Guidelines

“…In specific conditions such as chronic kidney disease, aerobic exercises associated with resistance exercise reduced the severity of WED 405 symptoms; but the studies comprised only small samples and the conclusions are still uncertain. A later meta-analysis in the same population confirmed that lower limb stretching exercises performed during dialysis were effective in reducing the severity of the symptoms of the disease 406 . A group of researchers investigated the therapies most commonly used by patients to improve and alleviate the symptoms of WED and found that deep massage was used as a therapy in approximately 77% of cases, although the relief was momentary 407 .…”

“…First, the interaction with the medical team for receiving supportive information about the proposed treatment is crucial. Second, several studies have shown significant improvements in the symptoms of WED and PLMD following the use of non-pharmacological therapies for their treatment [403][404][405][406][407][408] . Since WED improves with movement, the hypothesis that exercise improves the disease has been tested, with promising findings in different populations (Table 22).…”

Relation of Serum Hepcidin Levels and Restless Legs Syndrome in Patients Undergoing Peritoneal Dialysis

“…RLS seriously affects the life quality and prognosis of patients. Several studies had focused on pharmacological and nonpharmacological treatments of RLS and showed that gabapentin is the most effective pharmacologic intervention which also might improve sleep quality ( 22 ). However, there is still a lack of effective treatment measure ( 23 ), and it's important to understand the pathogenesis of RLS.…”

Five Things to Know About Restless Legs Syndrome in Patients on Dialysis

“…22 Cool dialysate (35.5°C) in comparison with standard (37°C) dialysate led to RLS severity score reduction and represents a reasonable choice of a nonpharmacological approach for patients with RLS on dialysis. 23 4. Intradialytic exercise with resistance training is safe, effective, and should be offered more regularly A.…”

“… 22 Cool dialysate (35.5°C) in comparison with standard (37°C) dialysate led to RLS severity score reduction and represents a reasonable choice of a nonpharmacological approach for patients with RLS on dialysis. 23 …”