An intervention to decrease sedentary behavior in older adults: A secondary analysis of a randomized controlled trial.

Background: Sedentary behaviors are associated with adverse health outcomes in older adults. The feasibility of behavioral interventions in this population is unclear. Methods: In the Sit Less, Interact, Move More (SLIMM) trial of 106 participants who had obesity, those randomized to the SLIMM intervention (N = 54) were instructed to replace sedentary activities with stepping. An accelerometer was used to measure physical activity. In this secondary analysis, mixed effect models were used to examine the effects of the SLIMM intervention on sedentary and stepping durations and steps/day by age (<70 and ≥ 70 years). Results: Mean ages in the <70 years (N = 47) and ≥70 years (N = 59) groups were 58 ± 11 and 78 ± 5. In the older subgroup, compared to standard-of-care (N = 29), the SLIMM intervention (N = 30) significantly increased stepping duration (13, 95%CI 1-24 min/d, p = 0.038) and steps per day (1330, 95% CI 322-2338, p = 0.01) and non-significantly decreased sedentary duration by (28,95% CI -61-5 min/d, p = 0.09). In the age <70 subgroup, there was no separation between the standard of care (N = 23) and SLIMM (N = 24) groups. Discussion: In older adults who had obesity, SLIMM intervention significantly increased stepping duration and steps per day. Interventions targeting sedentary behaviors by promoting low intensity physical activity may be feasible in this population.

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.

Association between the malnutrition-inflammation score and post-transplant anaemia.

BACKGROUND: Post-transplant anaemia (PTA) is common and is associated with adverse consequences. The protein-energy wasting (PEW) syndrome is associated with erythropoietin resistance in patients on maintenance dialysis. We assessed the association between PEW and PTA in a large prevalent cohort of stable kidney-transplanted patients. METHODS: Data from 942 prevalent kidney-transplanted patients were analysed. Socio-demographic parameters, laboratory results, transplantation-related data and medication were obtained from the charts. Biomarkers reflecting nutritional status and inflammation [serum leptin, albumin, interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and C-reactive protein] were measured. Anthropometric measures and the malnutrition-inflammation score (MIS) were also tabulated. Anaemia was defined according to the guidelines of the American Society of Transplantation. RESULTS: Mean age was 51 ± 13 years, 57% were males and 22% had diabetes. The prevalence of PTA was 33%. The haemoglobin (Hb) level significantly and negatively correlated with the MIS (rho = - 0.316), marginally with serum TNF-α (rho = - 0.079) and serum IL-6 (rho = - 0.075) and positively with serum transferrin (r = 0.298), serum albumin (r = 0.274), abdominal circumference (r = 0.254) and serum leptin (rho = - 0.152), P < 0.05 for all. In a multivariable linear regression model, MIS was independently associated with Hb (beta = - 0.118, P = 0.004) in patients with estimated glomerular filtration rate (eGFR) lower than or equal to 60 mL/min/1.73 m(2), but not in patients with higher eGFR. CONCLUSIONS: The MIS is independently associated with PTA in the kidney-transplanted population with eGFR lower than or equal to 60 mL/min/1.73 m(2).

Evaluation of the malnutrition-inflammation score in kidney transplant recipients.

BACKGROUND: Chronic protein-energy wasting, termed malnutrition-inflammation complex syndrome, is frequent in patients with chronic kidney disease and is associated with anemia, morbidity, and mortality in patients on maintenance dialysis therapy. The Malnutrition-Inflammation Score (MIS) recently has been developed and validated in dialysis patients. STUDY DESIGN: Observational cross-sectional study. SETTING & PARTICIPANTS: 993 prevalent kidney transplant recipients. PREDICTOR: MIS computed from change in body weight, dietary intake, gastrointestinal symptoms, functional capacity, comorbid conditions, decreased fat store/Systemic Global Assessment, signs of muscle wasting/Systemic Global Assessment, body mass index, serum albumin level, and serum transferrin level. OUTCOMES: Markers of inflammation and malnutrition, including serum C-reactive protein, interleukin 6, tumor necrosis factor alpha, serum leptin, prealbumin, body mass index, and abdominal circumference. The relationship was modeled by using structural equation models. RESULTS: Mean age was 51 +/- 13 years, 57% were men, and 21% had diabetes. Median time from transplant was 72 months. MIS significantly correlated with abdominal circumference (r = -0.144), serum C-reactive protein level (r = 0.094), serum interleukin 6 level (r = 0.231), and serum tumor necrosis factor alpha level (r = 0.102; P < 0.01 for all). A structural equation model with 2 latent variables (malnutrition and inflammation factor) showed good fit to the observed data. LIMITATIONS: Single-center study, lack of information about vascular access, presence of nonfunctioning kidney transplant, relatively high refusal rate. CONCLUSIONS: Our results confirm that MIS reflects both energy-protein wasting and inflammation in kidney transplant recipients. This simple instrument appears to be a useful tool to assess the presence of protein-energy wasting in this patient population.

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.

Association of Restless Legs Syndrome With Incident Parkinson's Disease.

Study Objectives: The association between restless legs syndrome (RLS) and Parkinson's disease (PD) has been extensively studied with inconclusive results; therefore, we prospectively examined the associations of the presence of RLS with development of incident PD. Methods: From a nationally representative prospective cohort of almost 3.5 million US veterans (age: 60 ± 14 years, 93% male, median follow-up time of 7.8 years [interquartile range: 6.4-8.4 years]), we created a propensity-matched cohort of 100882 PD-free patients and examined the association between prevalent RLS and incident PD. This association was also assessed in the entire cohort. Associations were examined using Cox models. Results: There were 68 incident PD events (0.13%, incidence rate 1.87 [1.48-2.37]/10000 patient-years) in the RLS-negative group, and 185 incident PD events (0.37%, incidence rate 4.72 [4.09-5.45]/10000 patient-years) in the RLS-positive group in the propensity-matched cohort. Prevalent RLS was associated with more than twofold higher risk of incident PD (hazard ratio [HR]: 2.57, 95% confidence interval [CI]: 1.95-3.39) compared to RLS-negative patients. Qualitatively similar results were found when we examined the entire 3.5 million cohort: Prevalent RLS was associated with more than twofold higher risk of incident PD (multivariable adjusted HR: 2.81, 95%CI: 2.41-3.27). Conclusion: RLS and PD share common risk factors. In this large cohort of US veterans, we found that prevalent RLS is associated with higher risk of incident PD during 8 years of follow-up, suggesting that RLS could be an early clinical feature of incident PD.

Sleep apnea is not associated with worse outcomes in kidney transplant recipients.

Obstructive sleep apnea(OSA) is one of the most common sleep disorders in kidney transplant recipients, however its long-term consequences have only rarely been investigated. Here, we hypothesized that the presence of OSA would be associated with higher risk of mortality and faster decline of graft function in kidney transplant recipients. In a prospective cohort study 100 prevalent kidney transplant recipients who underwent one-night polysomnography at baseline and were followed for a median 75 months. Generalized linear mixed-effects models and Cox regression models were used to assess the association between OSA and the rate of progression of chronic kidney disease(CKD) and mortality. The estimated slopes of estimated glomerular filtration rate(eGFR) in patients with and without OSA were compared using a two-stage model of eGFR change including only OSA as a variable. In this model patients with OSA (eGFR versus time was -0.93 ml/min/1.73 m(2)/yr(95%CI:-1.75 to-0.11) had a similar slope as compared to patients without OSA(eGFR versus time was -1.24 ml/min/1.73 m(2)/yr(95%CI: -1.67 to -0.81). In unadjusted Cox proportional regression analyses OSA was not associated with higher all-cause mortality risk (Hazard Ratio(HR) = 1.20; 95% Confidence Interval(CI): 0.50-2.85). No association was found between the presence of OSA and the rate of progression of CKD or all-cause mortality in prevalent kidney transplant recipients.

Quality of life and protein-energy wasting in kidney transplant recipients.

PURPOSE: Chronic kidney disease has profound effects on the health-related quality of life (HRQoL) of patients, with serious physiological, psychological and socio-economic implications. The co-occurrence of protein-energy wasting and inflammation in end-stage renal disease patients is associated with worse HRQoL and increased mortality. We designed this study to examine the relationship between nutritional and inflammatory status and HRQoL in kidney transplant recipients. METHODS: Data from 100 randomly selected kidney transplant patients were analyzed in a cross-sectional survey. Socio-demographic parameters, laboratory results, transplantation-related data, comorbidities, medication and malnutrition-inflammation score (MIS) (Kalantar Score) were tabulated at baseline. Patients completed the Kidney Disease Quality of Life-SF (KDQoL-SF™) self-administered questionnaire. RESULTS: Mean age was 51 ± 13 years, median (interquartile range, IQR) time since transplantation 66 (83) months, 57% were men, and 19% had diabetes. The median (IQR) MIS was 3 (3). The MIS significantly and negatively correlated with almost all HRQoL domains analyzed, and this association remained significant in multivariate linear regression analysis for the log-transformed scores on energy/fatigue (ß = -0.059 P < 0.001), bodily pain (ß = -0.056 P = 0.004), physical functioning (ß = -0.029, P = 0.022) and symptoms/problems (ß = -0.023 P = 0.005) domains after statistical correction for age, gender, eGFR, dialysis vintage, Charlson Comorbidity Index and occupational status. Additionally, cubic spline analyses revealed linearly increasing, "dose-response" relationship between almost all domains of KDQoL-SF™ and the MIS. CONCLUSIONS: Malnutrition-inflammation score is independently associated with different dimensions of HRQoL in kidney transplant recipients.

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.

Ropinirole treatment for restless legs syndrome.

In this paper we discuss therapy with ropinirole (known as adartrel in the United Kingdom) in patients with restless legs syndrome. Restless legs syndrome is characterized by an urge to move the legs, uncomfortable sensations in the legs and worsening of these symptoms during rest with at least temporary relief brought on by activity. Current recommendations suggest dopaminergic therapy (levodopa or dopamine receptor agonists like ropinirole) as the first-line treatment for restless legs syndrome. Based on the results of randomized, placebo-controlled, double-blind trials, we conclude that ropinirole is effective in reducing symptoms of restless legs syndrome in the general population. Ropinirole has no serious or common side effects that would limit its use significantly. Rebound and augmentation problems are relatively rarely seen with ropinirole, although properly designed comparative trials are still needed to address this question. It must be noted, however, that most published studies with ropinirole compare this drug with placebo. Very few studies have compared ropinirole with other drugs (L-dopa, gabapentin, opioids, benzodiazepines, other dopaminergic agents and selegiline hydrochloride). No cost-effectiveness trial has been published yet. Treatment of restless legs syndrome with ropinirole shows it to be effective, well-tolerated and safe and it can be used in restless legs syndrome in general.