Periodic limb movements in sleep are associated with stroke and cardiovascular risk factors in patients with renal failure.

Periodic limb movements in sleep (PLMS) is prevalent among dialysed patients and is associated with increased risk of mortality. Our study aimed to determine the prevalence of this disease in a sample of transplanted and waiting-list haemodialysed patients. One hundred transplanted and 50 waiting-list patients underwent polysomnography. Moderate and severe diseases were defined as periodic limb movements in sleep index (PLMSI) higher than 15 and 25 events h(-1), respectively. The 10-year coronary heart disease risk was estimated for all patients using the Framingham Score. Moreover, the 10-year estimated risk of stroke was calculated according to the modified version of the Framingham Stroke Risk Profile. PLMS was present in 27% of the transplanted and 42% of the waiting-list group (P = 0.094); the proportion of severe disease was twice as high in waiting-list versus transplanted patients (32 versus 16%, P = 0.024). Patients with severe disease had a higher 10-year estimated risk of stroke in the transplanted group [10 (7-17) versus 5 (4-10); P = 0.002] and a higher 10-year coronary heart disease risk in both the transplanted [18 (8-22) versus 7 (4-14); P = 0.002], and the waiting-list groups [11 (5-18) versus 4 (1-9); P = 0.032]. In multivariable linear regression models the PLMSI was associated independently with the Framingham cardiovascular and cerebrovascular scores after adjusting for important covariables. Higher PLMSI is an independent predictor of higher cardiovascular and cerebrovascular risk score in patients with chronic kidney disease. Severe PLMS is less frequent in kidney transplant recipients compared to waiting-list dialysis patients.

Association of the malnutrition-inflammation score with clinical outcomes in kidney transplant recipients.

BACKGROUND: The combination of chronic malnutrition and inflammation, often termed malnutrition-inflammation complex syndrome or protein-energy wasting, is common in patients with chronic kidney disease. It is associated with increased mortality in patients on maintenance dialysis therapy. We assessed the association of malnutrition-inflammation score (MIS) with all-cause mortality and death-censored transplant loss or death with a functioning transplant in a sample of kidney transplant recipients. STUDY DESIGN: Prospective prevalent cohort study. SETTING & PARTICIPANTS: Data from 993 prevalent transplant recipients were analyzed. Sociodemographic parameters, laboratory data, medical and transplant history, comorbid conditions, estimated glomerular filtration rate, and MIS were tabulated at baseline and annually thereafter. PREDICTOR: MIS, a 30-point scale expressed per 1 standard deviation (1 SD) unit or categorized as <3 (reference), 3-5, 6-8, and >8. The MIS is derived from 10 components, each with 4 levels of severity from 0 (normal) to 3 (severely abnormal). Higher score reflects more severe degree of malnutrition and inflammation status. OUTCOMES: All-cause mortality and death-censored transplant loss or death with a functioning transplant. Association of MIS with total mortality was assessed using time-dependent Cox regression analysis, and the association of MIS with death-censored transplant loss or death with a functioning transplant was assessed using semiparametric competing-risks regression analysis. RESULTS: Mean age was 51 ± 13 years, 57% of patients were men, and 21% had diabetes. Percentages of patients in the MIS categories <3, 3-5, 6-8, and >8 were 40%, 32%, 20%, and 8%, respectively. In multivariable time-dependent Cox regression analyses, time-varying MIS score was a significant predictor of all-cause mortality (HR per 1-SD increase, 1.59; 95% CI, 1.37-1.85), death with a functioning transplant (HR per 1-SD increase, 1.48; 95% CI, 1.23-1.78), and death-censored transplant loss (HR per 1-SD increase, 1.34; 95% CI, 1.04-1.71). Compared with MIS <3, HRs for all-cause mortality for MIS of 3-5, 6-8, and >8 were 1.53 (95% CI, 0.74-3.15), 3.66 (95% CI, 1.87-7.14), and 6.82 (95% CI, 3.34-13.91), respectively. LIMITATIONS: Single-center study, small number of outcomes. CONCLUSIONS: The MIS, a simple tool to assess the presence of malnutrition-inflammation complex syndrome, predicts mortality in kidney transplant recipients.

[Restless legs syndrome: the most prevalent "unknown" disorder]. / Nyugtalan láb szindróma: a leggyakoribb "ismeretlen" kórkép.

Sleep disorders are also considered as significant chronic disorders, as their physiological and psycho-social consequences are well documented. Restless legs syndrome has high prevalence, as it occurs in 5-10 % of the general population. Since clinical presentation is not well appreciated by many of the health care professionals, only a small proportion of the patients with restless legs syndrome is diagnosed and treated. The consequences of disease, however, are not negligible. The majority of the patients suffer from insomnia, impaired daytime functioning and quality of life. Although, restless legs syndrome is frequently characterized as a sleep disorder, it does not only influence sleep but also the daytime functioning of the patients. Additionally, restless legs syndrome causes not only subjective complaints and sleep disruption, but it is also associated with cardiovascular disorders.

Restless legs syndrome and mortality in kidney transplant recipients.

BACKGROUND: Previous studies showed an association between the presence of restless legs syndrome (RLS) and mortality in patients on dialysis therapy. An association between RLS and cardiovascular risk also was reported in the general population. However, no prospective study to date assessed the association between the presence of RLS and mortality in kidney transplant recipients. In a prospective cohort study (Transplantation and Quality of Life-Hungary Study), we tested the hypothesis that the presence of RLS predicts mortality in transplant recipients. STUDY DESIGN: Prospective cohort study was performed. SETTINGS & PARTICIPANTS: 804 kidney transplant recipients followed up at a single outpatient transplant center were enrolled in the study. Sociodemographic parameters, laboratory data, and medical history were collected at baseline. Data for 4-year outcomes were collected prospectively from patient charts. PREDICTOR: Presence of RLS assessed using the RLS Questionnaire. OUTCOME & MEASUREMENTS: We defined 3 primary outcomes: mortality with functioning graft, return to dialysis therapy, and the combined outcome of these 2. RESULTS: Mean age was 49 +/- 13 years, estimated glomerular filtration rate was 49 +/- 19 mL/min/1.73 m(2), and median time after transplantation was 54 months. During the 4 years, 97 patients died and 63 patients returned to dialysis therapy. Mortality at 4 years was significantly greater in patients who had RLS at baseline: univariate hazard ratio for the presence of RLS was 2.53 (95% confidence interval, 1.31 to 4.87). In multivariate Cox proportional hazard analysis, the presence of RLS significantly predicted mortality (hazard ratio, 2.02; 95% confidence interval, 1.03 to 3.95) after adjustment for several covariables. LIMITATIONS: The RLS Questionnaire was not validated in transplant recipients. We lacked information for key variables, including HLA mismatch, panel reactive antibodies, cold ischemic time, acute rejection episodes, viral infections, smoking status, and dyslipidemia. CONCLUSIONS: RLS, a potentially treatable disease, is a significant risk factor for mortality in kidney transplant recipients.

Restless legs syndrome, insomnia, and quality of life after renal transplantation.

OBJECTIVE: Restless legs syndrome (RLS) is associated with insomnia and impaired quality of life (QoL) in patients on maintenance dialysis; however, no information has been published on the association of RLS and QoL in kidney-transplanted patients. In a cross-sectional study, we analyzed the complex relationship between RLS, insomnia, and health-related QoL in kidney-transplanted patients. METHODS: In a cross-sectional survey at a single transplant center, 1067 patients were invited to participate. Complete data set was available from 785 kidney-transplanted patients. The RLS Questionnaire and the Athens Insomnia Scale were used to assess the prevalence of RLS and insomnia, respectively. QoL was measured using the Kidney Disease QoL-SF Questionnaire. RESULTS: Patients with RLS were three times more likely to have insomnia than patients without RLS (29% vs. 9%, P=.001), and the presence of RLS was a significant and independent predictor of insomnia in multivariate analysis. The presence of RLS was independently associated with impaired health-related QoL along several QoL domains after statistical adjustment for clinical and sociodemographic covariables. Importantly, this association remained significant even after adjusting for insomnia for some QoL domains. CONCLUSION: RLS is associated with poor sleep, increased odds for insomnia, and impaired QoL in kidney-transplanted patients. Our results suggest that both sleep-related and sleep-independent factors may contribute to the association of RLS and QoL.

Association of symptoms of insomnia and sleep parameters among kidney transplant recipients.

OBJECTIVE: Insomnia complaints are frequent among kidney transplant (kTx) recipients and are associated with fatigue, depression, lower quality of life and increased morbidity. However, it is not known if subjective insomnia symptoms are associated with objective parameters of sleep architecture. Thus, we analyze the association between sleep macrostructure and EEG activity versus insomnia symptoms among kTx recipients. METHODS: Participants (n1=100) were selected from prevalent adult transplant recipients (n0=1214) followed at a single institution. Insomnia symptoms were assessed by the Athens Insomnia Scale (AIS) and standard overnight polysomnography was performed. In a subgroup of patients (n2=56) sleep microstructure was also analyzed with power spectral analysis. RESULTS: In univariable analysis AIS score was not associated with sleep macrostructure parameters (sleep latency, total sleep time, slow wave sleep, wake after sleep onset), nor with NREM and REM beta or delta activity in sleep microstructure. In multivariable analysis after controlling for covariables AIS score was independently associated with the proportion of slow wave sleep (ß=0.263; CI: 0.026-0.500) and REM beta activity (ß=0.323; CI=0.041-0.606) (p<0.05 for both associations). CONCLUSIONS: Among kTx recipients the severity of insomnia symptoms is independently associated with higher proportion of slow wave sleep and increased beta activity during REM sleep but not with other parameters sleep architecture. The results suggest a potential compensatory sleep protective mechanism and a sign of REM sleep instability associated with insomnia symptoms among this population.

Insomnia in Patients With Chronic Kidney Disease.

Insomnia and poor self-perceived sleep are very common in patients with chronic kidney disease (CKD). Poor sleep is associated with fatigue, sleepiness, impaired daytime functioning, impaired health-related quality of life, and increased morbidity and mortality. Many illness- and treatment-related factors (metabolic changes, inflammation, altered sleep regulatory mechanisms, symptoms and complications of CKD, comorbid conditions, medications, and renal replacement therapies) may disturb sleep and contribute to the high prevalence of insomnia in this patient population. Accordingly, the approach to both diagnosing and treating this condition is quite complex. Although sleep-related problems are very important for patients with CKD, they largely are under-recognized and undertreated. Very few intervention trials provide an evidence base to support treatment decisions in this particular patient population. With this review we hope to increase awareness of insomnia among professionals involved in the management of patients with CKD and to provide guidance in recognizing and treating this important condition.

Obstructive sleep apnea and heart rate variability in male patients with metabolic syndrome: cross-sectional study.

BACKGROUND: Obstructive sleep apnea (OSA) is often accompanied by the metabolic syndrome. Because both conditions are associated with depressed heart rate variability (HRV) separately, our aim was to study whether co-morbid OSA is associated with more reduced HRV in male patients with the metabolic syndrome. METHODS: In this cross-sectional study, 35 men (age, 57±11 years) with the metabolic syndrome (according to International Diabetes Federation criteria) were included. OSA severity was defined by the apnea-hypopnea index (AHI). HRV was assessed by 24-hr ambulatory electrocardiographic monitoring. Standard deviation of all normal-to-normal RR intervals (SDNN), the high frequency power (HFP), and the ratio of low- to high-frequency power (LF/HF) were measured. RESULTS: There were 14, 6, and 8 cases of severe (AHI ≥30/hr), moderate (15/hr≤AHI <30/hr), and mild (5/hr ≤AHI <15/hr) OSA, respectively. Seven patients had no OSA. Patients with mild-moderate or severe OSA had reduced SDNN and HFP values compared to those without OSA. Increasing OSA severity was associated significantly with lower daytime LF/HF ratio [standardized ß regression coefficient (ß)=-0.362, P=0.043] and higher night/day LF/HF ratio (ß=0.377, P=0.023) after controlling for age, duration of diabetes, and severity of metabolic syndrome. CONCLUSIONS: Co-morbid OSA is associated with decreased overall HRV, parasympathetic loss, and impaired diurnal pattern of sympathovagal balance that may further increase the cardiovascular vulnerability of male patients with the metabolic syndrome. The role of the HRV analysis in the risk assessment of these patients warrants further studies.

Association between lunar phase and sleep characteristics.

OBJECTIVES: Popular belief holds that the lunar cycle affects human physiology, behavior, and health, including sleep. To date, only a few and conflicting analyses have been published about the association between lunar phases and sleep. Our aim was to analyze the relationship between lunar phases and sleep characteristics. METHODS: In this retrospective, cross-sectional analysis, data from 319 patients who had been referred for sleep study were included. Individuals with apnea-hypopnea index ≥ 15/h were excluded. Socio-demographic parameters were recorded. All participants underwent one-night standard polysomnography. Associations between lunar cycle (new moon, full moon and alternate moon) and sleep parameters were examined in unadjusted and adjusted models. RESULTS: Fifty-seven percent of patients were males. Mean age for men was 45 ± 14 years and 51 ± 12 years for women. In total, 224 persons had their sleep study done during alternate moon, 47 during full moon, and 48 during new moon. Full moon was associated with lower sleep efficiency [median (%) (IQR): new moon 82 (18), full moon 74 (19), alternate moon 82 (15); P < 0.001], less deep sleep [median (%) (IQR): new moon 9 (9), full moon 6 (4), alternate moon 11 (9); P < 0.001], and increased REM latency [median (min) (IQR): new moon 98 (74), full moon 137 (152), alternate moon 97 (76); P < 0.001], even after adjustment for several covariables. CONCLUSION: The results are consistent with a recent report and the widely held belief that sleep characteristics may be associated with the full moon.

Lack of association between objectively assessed sleep disorders and inflammatory markers among kidney transplant recipients.

PURPOSE: In patients on dialysis, the results of studies examining the association between sleep disorders and inflammation are controversial. We assessed the association between inflammatory markers and different sleep disorders in a large sample of kidney transplant recipients. METHODS: Cross-sectional study of 100 randomly selected kidney transplant patients who underwent one-night polysomnography ("sleep disorders evaluation in patients after kidney transplantation study") to diagnose obstructive sleep apnea (OSA) and periodic limb movements in sleep (PLMS). Athens Insomnia Scale (AIS) was utilized to assess the prevalence of insomnia. Sociodemographic information and data about medication, comorbidity and laboratory parameters were collected. Levels of inflammatory markers, such as C-reactive protein, serum albumin, white blood cell count, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), were measured. RESULTS: The mean age was 51 ± 13 years, 43% were women, and the prevalence of diabetes was 19%. We found no significant difference in the levels of inflammatory markers between patients with versus without OSA and PLMS. Apnea-hypopnea index showed a significant association with white blood cell count (ρ = 0.23), and weak (ρ < |0.15|), non-significant correlation with the other inflammatory markers. PLM index showed weak (ρ < |0.15|), non-significant correlation with all markers of inflammation. The serum IL-6 level was significantly higher in patients with insomnia (AIS ≥ 10) than in non-insomniacs [median (IQR): 3.2(2.6-5.1) vs. 1.7(1.2-2.9) ng/l; P = 0.009]. The levels of other inflammatory markers were similar between insomniacs and non-insomniacs. CONCLUSIONS: We did not find any association between the presence of objectively assessed sleep disorders and inflammatory markers in kidney transplant patients.

Association between the Malnutrition-Inflammation Score and depressive symptoms in kidney transplanted patients.

OBJECTIVE: Depressive symptoms and the Malnutrition-Inflammation Complex Syndrome (MICS) are prevalent in patients with chronic kidney disease. The complex relationship between MICS and depression has never been studied in kidney transplanted (Tx) patients. Here we evaluate the association between the Malnutrition-Inflammation Score (MIS) (Kalantar score) and depressive symptoms in Tx patients. METHODS: Cross-sectional data of 973 prevalent Tx patients were analyzed. Sociodemographic and anthropometric characteristics and clinical and laboratory data were collected, and serum levels of inflammatory markers [C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α)] were measured. The Center for Epidemiologic Studies-Depression (CES-D) scale, the MIS and the Charlson Comorbidity Index (CCI) were computed. We used linear regression analysis to examine whether the relationship between MIS and CES-D score is independent from sociodemographic and laboratory parameters. RESULTS: The CES-D score, corrected for age, gender and estimated glomerular filtration rate weakly but significantly correlated with serum IL-6 and the CCI (0.124 and 0.103, respectively; P<.05 for both) and marginally significantly with CRP (0.06; P=.06). We found a moderate correlation between CES-D score and MIS (0.262; P<.001). In a multivariable linear regression model, the MIS was independently associated with the CES-D score (B=0.110; P<.001). CONCLUSIONS: The MIS was significantly associated with depressive symptoms after adjusting for important covariables in patients after renal transplantation.

Sleep apnea is associated with cardiovascular risk factors among kidney transplant patients.

BACKGROUND AND OBJECTIVES: We assessed the prevalence of obstructive sleep apnea (OSA) and its clinical correlates in a large sample of patients who received a kidney transplant (Tx). We also compared the prevalence of the disorder between dialysis patients who were on the waiting list for a Tx (WL) and Tx patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a cross-sectional study of 100 Tx and 50 WL patients who underwent one-night polysomnography (SLeep disorders Evaluation in Patients after kidney Transplantation [SLEPT] Study). Sociodemographic information and data about medication, comorbidity, and laboratory parameters were collected. RESULTS: The prevalence of mild (apnea-hypopnea index [AHI] > or =5/h and <15/h), moderate (AHI > or =15/h and <30/h), and severe OSA (AHI > or =30/h) was 18, 11, and 14% in the Tx group and 28, 16, and 10% in the WL group, respectively. The AHI was significantly correlated with age (rho = 0.34), body mass index (rho = 0.45), neck circumference (rho = 0.4), abdominal circumference (rho = 0.51), and hemoglobin (rho = 0.24) in the Tx group. The proportion of Tx patients who were treated with three or more antihypertensive drugs was significantly higher in the OSA group (56 versus 31%; P = 0.022). Despite taking significantly more antihypertensive drugs, the average systolic BP was still higher in patients with versus without OSA (147 +/- 21 versus 139 +/- 18 mmHg; P = 0.059). CONCLUSIONS: The prevalence of OSA is similar in Tx and WL patients and it may contribute to presence of hypertension in patients who receive a Tx.

Association between restless legs syndrome and depression in patients with chronic kidney disease.

Restless legs syndrome (RLS) is reportedly associated with depression. This association may be mediated by both sleep-dependent and sleep-independent mechanisms. Here we analyze the association between RLS and depressive symptoms in patients with chronic kidney disease (CKD). We also assessed whether the relationship is independent of insomnia. In a cross-sectional study, socio-demographic parameters, laboratory data, and medical history were collected from 788 kidney transplant patients and 161 dialyzed patients. Insomnia, depression, and the presence of RLS symptoms were assessed with standard questionnaires. Patients with probable RLS had a higher prevalence of depressive symptoms than those without RLS (56% vs. 22% with vs. without RLS, respectively; P<.001). Patients presenting RLS symptoms had higher Athens Insomnia Scale (AIS) scores than patients without RLS [median AIS score (interquartile range): 7 (6) vs. 3 (4) with vs. without RLS, respectively; P<.001]. The AIS score correlated with the CES-D score (Spearman's rho=0.54, P<.001). In multivariate analysis, the presence of RLS symptoms was independently associated with depressive symptoms (OR=3.96, 95% CI 2.21-7.1, P<.001). This relationship remained significant even after including insomnia in the model (OR=2.9, CI 1.55-5.43, P<.001). The presence of RLS symptoms is associated with depression in patients with CKD. This relationship remained significant even after accounting for insomnia. Sleep-independent mechanisms may also contribute to the association between RLS and depression in patients with CKD.

High prevalence of patients with a high risk for obstructive sleep apnoea syndrome after kidney transplantation--association with declining renal function.

BACKGROUND: Obstructive sleep apnoea syndrome (OSAS) is much more prevalent in patients on dialysis than in the general population. Our aim was to assess for the first time the prevalence of patients with a high risk for OSAS and its clinical correlates in a large sample of kidney transplanted patients. We also wanted to compare the prevalence of the disorder between waitlisted dialysis patients (WL) and kidney transplanted patients (Tx). METHODS: One thousand sixty-seven kidney transplanted patients were asked to participate in a cross-sectional survey ('TransQoL-HU Study'). Socio-demographic data, history of renal disease, medication, comorbidity and laboratory parameters were collected at enrolment. Patients completed a battery of self-administered questionnaires including the Berlin Sleep Apnoea Questionnaire to assess risk status of OSAS. RESULTS: The final analyses included 841 Tx and 175 WL patients. The prevalence of high risk for OSAS was similar in the transplanted group vs WL patients (27% vs 33%). In multivariate logistic regression analysis male gender, older age, lower educational status, worse kidney function, use of hypnotic drugs and comorbidity were independent predictors for high risk of OSAS in kidney transplanted patients. CONCLUSIONS: High risk for sleep apnoea is highly prevalent in the kidney transplanted population. In addition to the well-known risk factors of OSAS (male gender, obesity, use of hypnotic drugs, comorbidity), impaired kidney function was also independently associated with high risk for OSAS.