Restless Legs Syndrome in Chronic Kidney Disease- a Systematic Review.
Yasaman Safarpour,
Nosratola D Vaziri,
Bahman Jabbari
Systematic Review
Tremor and other hyperkinetic movements (New York, N.Y.)
2023
32 цитирований
PubMed
DOI
CC-BY
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Study Design
- Тип исследования
- Systematic Review
- Вмешательство
- Restless Legs Syndrome in Chronic Kidney Disease- a Systematic Review. Dopaminergic drugs (levodopa, ropinirole, pramipexole, rotigotine); gabapentin; pregabalin; intraven
- Препарат сравнения
- Placebo
- Направление эффекта
- Mixed
- Риск систематической ошибки
- Unclear
Abstract
OBJECTIVES: The objective of this review is to provide updated information on the epidemiology, correlating factors and treatment of chronic kidney disease associated restless legs syndrome (CKD-A-RLS) in both adult and pediatric population. MATERIALS AND METHODS: We have reviewed the Medline search and Google Scholar search up to May 2022, using key words restless legs syndrome, chronic kidney disease and hemodialysis and kidney transplant. The reviewed articles were studied for epidemiology, correlating factors, as well as pharmacologic and non-pharmacologic treatment options. RESULTS: Our search revealed 175 articles, 111 were clinical trials or cross- sectional studies and 64 were review articles. All 111 articles were retrieved and studied in detail. Of these, 105 focused on adults and 6 on children. A majority of studies on dialysis patients reported a prevalence between 15-30%, which is notably higher than prevalence of RLS in general population (5-10%). The correlation between presence of CKD-A-RLS with age, gender, abnormalities of hemogram, iron, ferritin, serum lipids, electrolytes and parathyroid hormones were also reviewed. The results were inconsistent and controversial. Limited studies have reported on the treatment of CKD-A-RLS. Non-pharmacological treatment focused on the effect(s) of exercise, acupuncture, massage with different oils and infra-red light whereas, pharmacologic treatment options include the effects of dopaminergic drugs, Alpha2-Delta ligands (gabapentin and pregabalin), vitamins E and C, and intravenous iron infusion. CONCLUSION: This updated review showed that RLS is two to three times more common in patients with CKD compared to the general population. More patients with CKD-A-RLS demonstrated increased mortality, increased incidence of cardiovascular accident, depression, insomnia and impaired quality of life than those with CKD without RLS. Dopaminergic drugs such as levodopa, ropinirole, pramipexole and rotigotine as well as calcium channel blockers (gabapentin and pregabalin) are helpful for treatment of RLS. High quality studies with these agents are currently underway and hopefully confirm the efficacy and practicality of using these drugs in CKD-A-RLS. Some studies have shown that aerobic exercise and massage with lavender oil can improve symptoms of CKD-A- RLS suggesting that these measures can be useful as adjunct therapy.
Full Text
Figures
Tables
Table 1
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| MODE OF TREATMENT | NUMBER OF PATIENTS | TYPE OF STUDY | DURATION OF TREATMENT | RESULTS | SIDE EFFECTS |
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| Aerobic exercise [ | Treatment 7 | Prospective, Open label | 16 weeks | Reduced IRLS score by 42% | None |
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| Aerobic exercise [ | Treatment 13 | Prospective, Open label | 16 weeks | IRLS scores improved on week 16; no improvement of quality of life | None |
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| Glycerin and lavender oil massage [ | Glycerin 35 | Prospective | 45 minute, 3 times a week for one month | At the end of the study, both glycerin and lavender oil significantly improved symptoms (P < 0.05) | None |
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| Lavender oil and sweet orange oil massage [ | Lavender 35 | Double blind, Controlled | 3 weeks, | At the end of the study, both glycerin and sweet orange significantly improved symptoms (P < 0.001) | None |
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| Lavender oil massage [ | Lavender 21 | Double blind Controlled | 4 weeks | At the end of the study, lavender oil significantly improved symptoms (P < 0.0001) | None |
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| Lavender oil massage [ | Lavender 31 | Placebo Controlled | 10 minutes massage, 3 times per week for 4 weeks | RLS severity decreased and QoL improved significantly in the lavender group (P < 0.001) | None |
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| Lavender oil massage [ | Lavender 29 | Placebo Controlled | 10 minutes, 3 times per week | RLS severity significantly decreased in the lavender group (P < 0.0001) | None |
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| Application of infrared light at acuopoints [ | Treatment 30 | Single blind Prospective | 3 times per week for 3 weeks | Reduced IRLSRS scores but only during treatment | None |
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Table 2
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|---|---|---|---|---|
| NAME OF THE DRUG (S) | DESIGN OF STUDY | NUMBER OF PATIENTS, DOSE | RESULTS | SIDE EFFECTS |
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| Levodopa [ | Double blind, cross over for 4 weeks | 15, | Improved leg movements, PLM index, sleep quality and QoL (Ps < 0.03) | Dry mouth and headaches |
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| Gabapentin [ | Double blind, crossover for 4 weeks (1 week wash out) | 15, | 11 patients responded to gabapentin,1 to both placebo and gabapentin | Two drop-outs, one due to lethargy, one due to MI (unrelated to drug) |
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| Rotigotine patch, | Single center | 14, | Improved: severity of Symptoms (p < 0.003), QoL (P < 0.001, sleep (P < 0.001). | One patient:GI upset, no augmentation |
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| Gabapentin [ | Single center, | 59: GP | No effect | In gabapentin group, 17% discontinued treatment |
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| Rotigotine patch [ | Double blind, placebo controlled | 15 Rotigotine | At the end of study: 10 of 15 and 2 of 10 showed significant improvement of RLS score in Rotigotine and placebo groups, respectively. | Nausea 20% |
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| Low dose ropinirole vs aerobic exercise vs placebo | Partially, double blind/placebo controlled | 0.25 mg ropinirole, 2 h before sleep, 45 minutes cycling during each HD session | Ropinirole and aerobic exercise equally improved IRLS scores, QoL and depression. Ropinirole improved sleep quality | No side effects |
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| Gabapentin (GP) versus Levodopa (LD) | Double blind | GP: 42 | Both reduced IRLS scores but GP was more effective (P < 0.016). Both improved quality of sleep | Transient hypotension in two patients who took Levodopa. Increased day time sleepiness GP > LD |
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| Gabapentin (GP) versus Levodopa (LD) | Observational | GP: 14 | IRLSS score was significantly improved after both Gabapentin and Levodopa treatment | Not mentioned |
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| Gabapentin versus levodopa [ | Open label | GP# 15 | Both improved IRLSS scores. Gabapentin was superior to levodopa in improving sleep quality and latency, QoL (measured by SF36), general health and body pain | One patient dropped from the study due to gabapentin side effect (type not mentioned). |
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| Ropinirole versus levodopa-SR [ | Randomized, cross-over | 10 | At the end of study, ropinirole was superior to levodopa regarding improving scores of six item IRLS and increasing sleep time (P < 0.001) as well as improvement of clinical impression scorea (P < 0.01) | One patient taking levodopa withdrew from the study due to vomiting |
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Table 3
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|---|---|---|---|---|---|
| TYPE OF VITAMIN | NUMBER OF PATIENTS | STUDY DESIGN | DOSE AND DURATION OF TREATMENT | RESULTS | SIDE EFFECTS |
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| C and E [ | 60 | Double blind-placebo controlled | Vitamin C: 200 mg/day | At 8 weeks, patients treated with vitamin C or E or both demonstrated significant reduction of IRLS score compared to placebo. The difference between vitamin treated groups was not significant. | none |
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| Intravenous Vitamin C [ | 90 | Double blind placebo controlled | Intravenous Vitamin C, three times per week (given at the end of dialysis session for 8 weeks. | Quality of sleep and RLS scores improved significantly in patients who received vitamin C. | None |
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| Compared Vitamin C with pramipexole [ | 45 | Double blind placebo controlled | Vitamin C: 250 mg | Both Vitamin C and Pramipexole groups demonstrated significant improvement of IRLS scores after treatment (P < 0.001). | One patient in the pramipexole developed nausea and vomiting and excluded |
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Table 4
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|---|---|---|---|---|---|
| TREATMENT | NUMBER OF PATIENTS | STUDY DESIGN | DOSE, DURATION | RESULTS | SIDE EFFECTS |
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| Intravenous (IV) iron dextran [ | 25 | Double blind- placebo controlled | Iron dextran: 1000 mg | At weeks 1 and 2 post-injection, patients in the Iron treated group showed significant reduction of IRLS scores (P = 0.01 and P = 0.03). At week 4, though still lower than placebo, the difference was not statistically significant | No difference in adverse effects between the two groups |
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| Intravenous iron sucrose [ | 30 | Randomized, placebo-controlled | Iron sucrose: 100 mg, three times/week for a total of 1000 mg. Study duration: 3 weeks | After two weeks, IRLS scores (compared to baseline) were significantly reduced compared to placebo group (P = 0.000). Improvement of IRLS score in the iron group continued for 4–24 weeks. | No adverse effects |
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| Intravenous iron sucrose [ | 18 | Double blind- placebo controlled | 500 mg of Iron sucrose was administered IV in two successive days for a total of 1000 mg | The trial was aborted half- way into the study since despite some improvement in GRS (at two weeks), authors predicted lack of robust response at the end of the study | Edema in either hands or feet (36%). Nausea or vomiting (36%). Hypotension (18%). dizziness (18%). abdominal pain (9%). All noted during infusion only. |
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Table 5
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|---|---|---|---|---|
| AUTHORS AND DATE | NUMBER OF PATIENTS | DRUG, DOSE, STUDY DURATION | RESULTS | SIDE EFFECTS |
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| *Walters et al, 1993 [ | 11 | Oxycodone, 5 mg tablets, average dose 15.9 mg/day | Patients rated improvement on the scale of 1–4: leg sensations, daytime sleepiness, motor restlessness and PLS. All Significantly improved (P < 0.5), | Mild constipation: two patients, mild lethargy: 1 patient |
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| **Trenkwalder et al, 2009 [ | 267 | Oxycodone/Naloxone | Mean International RLS Study group severity rating scale Sum score significantly improved in oxycodone group | Serious adverse effects: 3 in the double blind phase, 3 in the extension phase.(not specified). |
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Table 6
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| |
|---|---|
| 1 | An irresistible urge to move the legs, usually but not always accompanied by uncomfortable and unpleasant sensations in the legs |
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| 2 | Symptoms that begin or worsen during the periods of inactivity, such as lying down or sitting |
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| 3 | Symptoms are partially or totally relieved by movement |
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| 4 | Symptoms only occur and are worse in the evening or night than during the day |
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| 5 | The occurrence of the described features is not solely accounted for as symptoms primary to another medical or a behavioral condition (myalgia, venous stasis, leg edema, arthritis, leg cramps, positional discomfort, habitual foot tapping). The criteria published earlier in 2003 lacks the 5th criteria. |
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Table 7
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|---|---|---|
| DRUG’S NAME | BASED ON CREATINE CLEARANCE (ML/MINUTE) | RECOMMENDED DOSE GIVEN IN THREE DIVIDED DOSES IN ALTERNATE DAYS |
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| Gabapentin | 50–79 | 600–180 mg |
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| 30–49 | 300–900 mg | |
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| 15–29 | 150–600 | |
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| <15 | 150–300 | |
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| Pregabalin | Based on eGFR, mL/min/1.73 m2 | |
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| 30–60 | Initially 75 mg, maximum 300 mg daily | |
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| 15–30 | Initially 25–50 mg, maximum 300 mg in two divided doses | |
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| <30 | Initially 25 mg once daily and maximum 75 mg once daily | |
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