Table 1.

Quality Assessment of Included Studies for Mortality in RLS

Study	Population (n)	Follow-up (years)	RLS assessment	Outcome hazard ratio (95% CI)	Confounding factors adjustment	Disadvantages	Disadvantages
Pollak, et al.38	Elderly community-based population (1,885)	3.5	Self-administered sleep questionnaire	Females:1.36 (0.94–1.96) Males: 0.92 (0.60–1.42).	Age, Activities of daily living (ADL) problems, self-assessed health, income, cognitive impairment, depression, living alone, insomnia	The first prospective study analyzing survival in RLS urban-based community	Limited RLS diagnostic accuracy
Winkelman et al.36	End-stage renal disease-based population (204)	2.5	Self-administered sleep questionnaire	1.85 (1.12–3.07)	Age, sex, number of years of dialysis	Large sample and novel information (independent association of RLS with discontinuation of dialysis)	Clinic-based sample, limited RLS diagnostic accuracy
Unruh et al.37	Dialysis-based population (894)	3	Self-administered sleep questionnaire	1.39 (1.08–1.79)	Age, race, sex, dialysis mode, insulin-requiring diabetes, comorbidity and Karnofsky indexes, and center	Inclusion of patients with other types of dialysis, ethnic populations, and treatments information	Limited diagnostic accuracy
Molnar et al.31	Kidney-transplantation recipients-based population (804)	4	RLS questionnaires	2.02 (1.03–3.95)	Diabetes, arterial hypertension, transplantation vintage, glomerular filtration rate, serum albumin, hemoglobin, C-reactive protein	Large sample size, novel information (association of RLS with kidney transplant recipients),	Limited information on cardiovascular confounders, selection bias due to high proportion of missing data (25%)
Mallon et al.40	Community-based population (5,102)	20	Upsala Sleep Inventory	Females:1.85 (1.20–2.85) Males:0.81 (0.51–1.28)	Age, short nigh sleep time, lifestyle factors (living alone), medical conditions such as smoking, habitual snoring, BMI ≥ 30, hypertension, heart disease, diabetes, asthma, and depression	Community-based population, large sample size, high response rate	Limited diagnostic accuracy, lack of information on treatments
La Manna et al.32	End-stage renal disease patients on dialysis-based population (100)	1.5	RLS Study Group diagnostic criteria	6.29 (1.74–22.79)	Age, gender, BMI, comorbidity index, albumin, residual diuresis	Novel information (need of phenotyping intermittent vs. continuous RLS and inflammatory markers)	Limited follow-up
Li et al.33	Community-based population (18,425)	8	RLS diagnostic index	Men:1.92 (1.03–3.56)	Age, ethnicity, body mass index, life style factors (smoking, alcohol, and physical activity), chronic conditions (cancer, hypertension, cardiovascular disease and other comorbidities), sleep disorders and duration	Large sample size and exclusion of RLS mimics	Selection bias (relatively healthy Caucasian male population with access to health care)
Lin et al.34	End-stage renal disease patients-based population (1,093)	3	RLS diagnostic index	1.53 (95% CI 1.07–2.18)	Age, sex, duration of dialysis, comorbidity of diabetes mellitus, comorbidity of hypertension, serum hemoglobin level, transferrin saturation, serum iron level, and the numbers of cardio-/cerebrovascular events	Large survey of RLS in dialysis patients, inclusion of clinical laboratory data, and medical record review
Stefanidis et al.35	End-stage renal disease-based population (579)	3	RLS Study Group diagnostic criteria	0.66 (0.41–1.06)	Age, sex, diabetic nephropathy, duration of dialysis, dialysis mode, body mass index, serum urea before hemodialysis (HD), urea reduction ratio, Kt/V, β2-microglobulin, C-reactive protein, albumin, hemoglobin, serum iron, ferritin, transferrin, transferrin saturation, calcium, phosphorus, parathyroid hormone	Large sample size, RLS diagnostic accuracy	Lack of information on mortality ascertainment and kidney transplantation during follow-up
Molnar et al.5	Community-based population (3,000,000)	8	ICD-9 code	1.88 (1.70–2.08)	Age, gender, race/ethnicity, income, marital status, baseline estimated glomerular filtration rate, comorbidities at baseline (diabetes, hypertension, cardiovascular disease, heart failure, cerebrovascular disease, peripheral vascular disease, lung disease, dementia, rheumatic disease, malignancy, HIV/AIDS, depression, presence of obstructive sleep apnea and presence of periodic limb movements in sleep, and BMI	Large sample size, and event numbers	Limited RLS diagnostic accuracy Use of propensity score method
Ricardo et al.41	Non-institutionalized community-based population (1,470)	3	Sleep Hear Health Study Habits Questionnaire and Functional Outcomes of Sleep Questionnaire	1.69 (1.04–2.75)	Diabetes, hypertension, tobacco, hypnotic consumption, congestive heart failure, depression, BMI, age, sex, race, ethnicity, income, glomerular filtration, and albuminuria	Large sample size and follow-up	Limited diagnostic accuracy, exclusion of subjects with missing creatinine/urine albumin data
DeFerio et al.39	End-stage renal disease patients on dialysis-based population (1,456,114)	2	ICD-9 code 333.94	1.16 (0.88–1.44)	Age, sex, race, ethnicity, vascular access type, BMI, serum albumin level, coronary artery disease, congestive heart failure, cerebrovascular disease, peripheral vascular disease, hypertension, diabetes, cancer, major depressive disorder, dysthymic disorder, anxiety, and tobacco dependence	Large sample size	Limited diagnostic accuracy and number of deaths during follow-up
Li et al.4	Community-based population (57,417)	10	Single RLS item question	Women: Total mortality 1.15 (0.98–1.34) Cardiovascular mortality 1.43 (1.02–2.00)	Age, race, smoking status, BMI, physical activity, alcohol consumption, sleep duration, and snoring frequency; history of major chronic diseases (arthritis, diabetes mellitus, hypertension, hypercholesterolemia, Parkinson’s disease, and use of vitamin supplements, aspirin, antidepressant drugs, and antihypertensives)	Large sample size and follow-up	Selection bias (exclusion of not ever diagnosed with RLS by physicians, recall bias), and lack of renal and neuropathy information

Abbreviations: ADL; BMI, Body Mass Index; CI, Confidence Interval; HD.