Iron status and chronic kidney disease predict restless legs syndrome in an older hospital population

Quinn, Colin; Uzbeck, Mateen; Saleem, Imran; Cotter, Paul; Javed, Ali; O'Malley, G; Gilmartin, J J; O’Keeffe, Shaun T.

doi:10.1016/j.sleep.2010.08.014

Cited by 38 publications

(21 citation statements)

References 42 publications

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“…Some studies suggest negatively effect of smoking and alcohol consumption on RLS in ESRD patients [37] whereas the others and our study have not demonstrated this relation [30,38,39]. The role of serum calcium, phosphorus and intact parathormone levels in uremic RLS are controversial.…”

Section: Discussioncontrasting

confidence: 69%

Prevalence of Restless Legs Syndrome in Patients Treated with Peritoneal Dialysis: Clinical and Biochemical Characteristics among Patients with and without Restless Legs Syndrome

Korkmaz¹,

Tokgöz²,

İsmailoğulları³

et al. 2013

OJNeph

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Introduction and Aims: This is a prospective study identifying prevalence of Restless Legs Syndrome (RLS) in patients ongoing peritoneal dialysis (PD) due to end stage renal disease (ESRD) and comparing clinical and biochemical characteristics among patients with and without RLS. Methods: Two hundred ESRD patients who received PD at least six months assessed by neurologist and nephrologist with regards to presence of RLS. Also, clinical and biochemical features of these patients are determined. One hundred and forty four patients were excluded from study because they had other secondary causes of RLS except for ESRD. Results: Thirteen of 56 patients (23.2%) had RLS. The use of vitamin B + folic acid supplements was significantly lower in patients with RLS than in those without RLS (69.2% vs 97.7%; p = 0.008). There was no significant difference between patient groups with and without RLS in terms of age, gender, body mass index, cause of ESRD, peritoneal membrane transport characteristic, smoking, consuming alcohol, use of erythropoietin, duration of PD, hemoglobin, serum calcium, serum phosphorus, serum albumin, levels of serum iron, total iron binding capacity, ferritin, folic acid and vitamin B12, transferrin saturation, weekly Kt/V urea value, and amount of residual urine volume (p > 0.05). Conclusion: RLS is more common among PD patients than general population. Although essential cause is not exactly known, use of folic acid and vitamin B complex decrease the RLS prevalence in this particular patient group.

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Section: Discussioncontrasting

confidence: 69%

Prevalence of Restless Legs Syndrome in Patients Treated with Peritoneal Dialysis: Clinical and Biochemical Characteristics among Patients with and without Restless Legs Syndrome

Korkmaz¹,

Tokgöz²,

İsmailoğulları³

et al. 2013

OJNeph

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“…Iron-deficiency anemia is a well-known risk factor for idiopathic RLS, and the association between the level of serum ferritin and RLS suggests a close relationship between iron metabolism and pathogenetic mechanism of RLS. 37,38 However, one of the included studies in our work showed no statistically significant difference in serum iron and ferritin between CKD patients with and without RLS.…”

Section: Discussionmentioning

confidence: 51%

Prevalence of restless legs syndrome in chronic kidney disease: a systematic review and meta-analysis of observational studies

et al. 2016

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Introduction: Nowadays prevalence of restless legs syndrome (RLS) in chronic kidney disease (CKD) patients was reported in many studies, while the results varied. The aim of our study was to investigate the prevalence of RLS in this population, considering different data collecting measures and diagnostic criteria. Methods: MEDLINE, Embase, PsycINFO, and Scopus databases were searched for relevant studies. We limited the analyses to studies using clinical interview or questionnaire for diagnosis. Univariate meta-regression analysis was preformed to assess the effects of the disease-related covariates on prevalence estimates. Comprehensive Meta-Analysis 2.0 was used to perform the meta-analysis. Results: Fifty-one studies were included in the analysis. Prevalence of RLS was varied by renal function and diagnostic methods. Overall prevalence in CKD populations was 24.2% (95%CI, 20.1-28.7). Pooled prevalence of RLS was higher in patients diagnosed by questionnaire than by clinical interview [26.2% (95%CI, 17.9-36.5) vs. 23.6% (95%CI, 19.6-28.1)]. When grouped by CKD setting, the prevalence was 28.4% (95%CI, 24.6-32.6) in dialysis patients, followed by early stages patients [9.9% (95%CI, 5.4-17.5)], and kidney transplant recipients [6.7% (95%CI, 5.6-7.8)]. Conclusions: Our meta-analysis suggested that more than one-quarter of CKD sufferers, especially those who were on dialysis, were plagued by RLS. Higher sensitivity of diagnostic criteria in interview may be valuable for timely treatment.

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“…[22][23][24][25] Recently, low serum ferritin was described as a significant predictor of RLS in 301 hospital patients older 50 years of whom 55 had RLS. 26 On the other hand, cross-sectional studies on 365, 701, and 714 individuals from German, 2 Tyrolean, 3 and Korean 27 population cohorts with 36, 74, and 59 RLS cases, respectively, did not show an association to serum ferritin. The same was true for most other serum iron parameters except for the soluble transferrin receptor in the study that included 74 RLS patients.…”

Section: Discussionmentioning

confidence: 94%

Dilution of candidates: the case of iron-related genes in restless legs syndrome

et al. 2012

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Restless legs syndrome (RLS) is a common multifactorial disease. Some genetic risk factors have been identified. RLS susceptibility also has been related to iron. We therefore asked whether known iron-related genes are candidates for association with RLS and, vice versa, whether known RLS-associated loci influence iron parameters in serum. RLS/control samples (n ¼ 954/1814 in the discovery step, 735/736 in replication 1, and 736/735 in replication 2) were tested for association with SNPs located within 4 Mb intervals surrounding each gene from a list of 111 iron-related genes using a discovery threshold of P ¼ 5 Â 10 À4 . Two population cohorts (KORA F3 and F4 with together n ¼ 3447) were tested for association of six known RLS loci with iron, ferritin, transferrin, transferrin-saturation, and soluble transferrin receptor. Results were negative. None of the candidate SNPs at the iron-related gene loci was confirmed significantly. An intronic SNP, rs2576036, of KATNAL2 at 18q21.1 was significant in the first (P ¼ 0.00085) but not in the second replication step (joint nominal P-value ¼ 0.044). Especially, rs1800652 (C282Y) in the HFE gene did not associate with RLS. Moreover, SNPs at the known RLS loci did not significantly affect serum iron parameters in the KORA cohorts. In conclusion, the correlation between RLS and iron parameters in serum may be weaker than assumed. Moreover, in a general power analysis, we show that genetic effects are diluted if they are transmitted via an intermediate trait to an end-phenotype. Sample size formulas are provided for small effect sizes. Keywords: restless legs syndrome; iron parameters; MEIS1 haplotype; power calculation; linear regression; logistic regression INTRODUCTIONRestless legs syndrome (RLS) 1 is a sensory-motor disorder characterized by an urge to move and unpleasant sensations in the lower limbs at rest. In Caucasians, RLS is present in up to 10% of the population. 2,3 Pregnancy, uremia, celiac disease, and iron deficiency are considered to be risk factors. 4 RLS also has a considerable heritability and is associated with multiple genetic risk factors. Genome-wide association studies 5-10 identified variants in six loci encompassing the genes MEIS1, BTBD9, MAP2K5/SKOR1, PTPRD, and TOX3/non-coding RNA.Aiming for the identification of further genetic risk factors of RLS, we addressed the apparent relation of RLS susceptibility to iron metabolism and iron availability 11 that has been explained by cerebral iron being crucial in the etiology of RLS. 12 We therefore tested the SNPs at the loci of a candidate set of genes known to be involved in iron metabolism for association with RLS. Vice versa, we asked whether RLS genes are involved in iron metabolism because the RLSassociated SNP rs3923809 at the BTBD9 locus has previously been reported to be associated with the serum level of ferritin in a study on RLS subjects and their relatives. 6

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Iron status and chronic kidney disease predict restless legs syndrome in an older hospital population

Cited by 38 publications

References 42 publications

Prevalence of Restless Legs Syndrome in Patients Treated with Peritoneal Dialysis: Clinical and Biochemical Characteristics among Patients with and without Restless Legs Syndrome

Prevalence of Restless Legs Syndrome in Patients Treated with Peritoneal Dialysis: Clinical and Biochemical Characteristics among Patients with and without Restless Legs Syndrome

Prevalence of restless legs syndrome in chronic kidney disease: a systematic review and meta-analysis of observational studies

Dilution of candidates: the case of iron-related genes in restless legs syndrome

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