Association Between Serum Leptin Level and Mortality in Kidney Transplant Recipients.

OBJECTIVE: Leptin is a hormone made by adipocytes and associated with hypertension, inflammation, and coronary artery disease. Low serum leptin level was associated with higher risk of death in patients with advanced chronic kidney disease. Little is known about the association of serum leptin with outcomes in kidney transplant recipients. DESIGN: Prospective prevalent cohort. SETTING AND SUBJECT: We collected sociodemographic and clinical parameters, medical and transplant history, and laboratory data of 979 prevalent kidney transplant recipients. Associations between serum leptin level and death with a functioning graft, all-cause death, and death-censored graft loss over a 6-year follow-up period were examined in survival models. RESULTS: Serum leptin levels showed moderate negative correlation with eGFR (R = -0.21, P < .001) and positive correlations with BMI (R = 0.48, P < .001) and C-reactive protein (R = 0.20, P < .001). Each 10 ng/mL higher serum leptin level was associated with 7% lower risk of death with functioning graft (hazard ratio [HR] (95% confidence interval [CI]), 0.93 (0.87-0.99)), and this association persisted after adjustment for confounders: HR (95% CI), 0.90 (0.82-0.99). Similar associations were found with all-cause death as outcome. The association between serum leptin level and risk of graft loss was nonlinear, and only low serum leptin level was associated with higher risk of graft loss. CONCLUSIONS: In prevalent kidney transplant recipients, lower serum leptin was an independent predictor of death.

Association between serum resistin level and outcomes in kidney transplant recipients.

Resistin is an adipocytokine that is associated with inflammation, coronary artery disease, and other types of cardiovascular disease among patients with normal kidney function. However, little is known about the association of resistin with outcomes in kidney transplant recipients. We collected socio-demographic and clinical parameters, medical and transplant history, and laboratory data from 988 prevalent kidney transplant recipients enrolled in the Malnutrition-Inflammation in Transplant-Hungary Study (MINIT-HU study). Serum resistin levels were measured at baseline. Associations between serum resistin level and death with a functioning graft over a 6-year follow-up period were examined in unadjusted and adjusted models. The mean±SD age of the study population was 51 ± 13 years, among whom 57% were men and 21% were diabetics. Median serum resistin concentrations were significantly higher in patients who died with a functioning graft as compared to those who did not die during the follow-up period (median [IQR]: 22[15-26] vs. 19[14-22] ng/ml, respectively; P < 0.001). Higher serum resistin level was associated with higher mortality risk in both unadjusted and fully adjusted models: HRs (95% CI): 1.33(1.16-1.54) and 1.21(1.01-1.46), respectively. In prevalent kidney transplant recipients, serum resistin was an independent predictor of death with a functioning graft.

Circulating Angiopoietin-2 levels predict mortality in kidney transplant recipients: a 4-year prospective case-cohort study.

Angiopoietin 2 (Angpt2) impairs endothelial function by preventing angiopoietin 1 from binding to their common endothelial-specific receptor Tie2. Here, we examined whether circulating Angpt2 predicts outcome in kidney transplant recipients. For this case-cohort study, we selected 130 kidney transplant recipients who had died or returned to dialysis within the first 2 years of follow-up of our cohort study, as well as 130 age- and gender-matched kidney transplant recipients without an event (controls) from a total of 993 kidney transplant recipients. The total of 260 selected patients were followed in median 4 years. Serum Angpt2 at baseline was measured using an in-house immunoluminometric assay. Median Angpt2 concentrations were significantly higher in patients who died [median (interquartile range--IQR) 3.6 (2.8-5.9) ng/ml] as compared to patients who did not die during the study period [2.8 (2.1-4.1) ng/ml; P < 0.001]. Ln (natural log) Angpt2 levels correlated positively with C-reactive protein levels (r = 0.315, P < 0.001) and the Charlson Comorbidity Index (r = 0.188, P = 0.002) and were inversely associated with eGFR (r = -0.301, P < 0.001) hemoglobin (r = -0.269, P < 0.001), and serum albumin concentrations (r = -0.382, P < 0.001). On multivariate analyses, baseline Angpt2 levels independently predicted all-cause mortality (multivariable-adjusted hazard ratio associated with one natural log unit higher Angpt2 level: 1.70 (95% confidence interval: 1.10-2.61)). In our analysis, circulating Angpt2 was an independent predictor of all-cause mortality in stable, prevalent kidney transplant recipients.

Renal function is independently associated with red cell distribution width in kidney transplant recipients: a potential new auxiliary parameter for the clinical evaluation of patients with chronic kidney disease.

Red cell distribution width (RDW), a measure of heterogeneity in the size of circulating erythrocytes, reportedly predicts mortality. Similarly to RDW, impaired renal function is also associated with inflammation and protein-energy wasting. This study assessed if renal function is associated with RDW independent of relevant confounders in stable kidney transplant recipients. We examined the association between RDW and estimated glomerular filtration rate (eGFR) in a cohort of 723 prevalent kidney transplanted recipients who were not receiving erythropoietin-stimulating agents. Associations were examined in regression models adjusted for age, sex, comorbidity, blood haemoglobin, iron indices, markers of nutritional status and inflammation, markers of bone and mineral metabolism and the use of immune suppressants. Lower eGFR was significantly associated with higher RDW (r = -0·382, P < 0·001). This association remained highly significant even after multivariate adjustments where 10 ml/min decrease in the eGFR was significantly associated with an increase of the RDW values (B10 ml/min decrease  =  0·078; 95% confidence interval: 0·044-0·111). The results were consistent in subgroups of patients with different levels of haemoglobin, chronic kidney disease status and various markers of inflammation and iron status. Lower eGFR is associated with higher RDW, independent of comorbidity, iron deficiency, inflammation and nutritional status in kidney transplant recipients.

Periodic limb movements in sleep are linked to decreased hippocampus and amygdala volumes in the population-based BiDirect Study.

STUDY OBJECTIVES: Even though numerous studies indicate that sleep disorders are associated with altered brain morphology, MRI studies focusing on periodic limb movements in sleep (PLMS) are scarce. Our aim was to investigate the association of PLMS with global and regional gray matter volumes as well as white matter hyperintensity (WMH) volume. METHODS: One hundred and eighty-nine subjects (57.0 ± 7.8 years, women: 50.5%) of the population-based BiDirect Study underwent a single-night polysomnography (PSG). Standard criteria of the American Academy of Sleep Medicine were applied to evaluate sleep characteristics and calculate the PLMS index (PLMSI). T1w and FLAIR images were acquired with cerebral MRI at 3 Tesla. Voxel-based morphometry was performed to determine the total gray matter volume as well as the volume of cortical segments and subcortical gray matter areas using SPM12 and CAT12. The WMH volume was quantified with the Brain Intensity AbNormality Classification Algorithm. The independent relationship between MRI markers and PLMSI was analyzed using multivariable linear regression with adjustment for age, sex, body mass index, intracranial volume, PSG scorer, PSG device, sleep apnea, and the use of antidepressants. RESULTS: PLMSI was not significantly related to global gray matter volume and WMH volume. However, significant inverse associations of the PLMSI with the volume of the hippocampus (left and right hemisphere) and left amygdala were observed. CONCLUSIONS: A significant relationship between a higher PLMSI and lower volumes of the hippocampus and amygdala was found among the participants of the BiDirect Study. Since these associations are based on exploratory analyses, further replications are required before drawing firm conclusions.

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.

Elevated fibroblast growth factor 23 is a risk factor for kidney transplant loss and mortality.

An increased circulating level of fibroblast growth factor 23 (FGF23) is an independent risk factor for mortality, cardiovascular disease, and progression of chronic kidney disease (CKD), but its role in transplant allograft and patient survival is unknown. We tested the hypothesis that increased FGF23 is an independent risk factor for all-cause mortality and allograft loss in a prospective cohort of 984 stable kidney transplant recipients. At enrollment, estimated GFR (eGFR) was 51 ± 21 ml/min per 1.73 m(2) and median C-terminal FGF23 was 28 RU/ml (interquartile range, 20 to 43 RU/ml). Higher FGF23 levels independently associated with increased risk of the composite outcome of all-cause mortality and allograft loss (full model hazard ratio: 1.46 per SD increase in logFGF23, 95% confidence interval: 1.28 to 1.68, P<0.001). The results were similar for each component of the composite outcome and in all sensitivity analyses, including prespecified analyses of patients with baseline eGFR of 30 to 90 ml/min per 1.73 m(2). In contrast, other measures of phosphorus metabolism, including serum phosphate and parathyroid hormone (PTH) levels, did not consistently associate with outcomes. We conclude that a high (or elevated) FGF23 is an independent risk factor for death and allograft loss in kidney transplant recipients.

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.

Health-related quality of life and clinical outcomes in kidney transplant recipients.

BACKGROUND: Health-related quality of life (HRQoL) is an important outcome measure in patients with chronic kidney disease. It also has been shown repeatedly to predict mortality in various patient populations. In a prospective cohort study, we assessed the association between HRQoL and long-term clinical outcome in kidney transplant recipients. STUDY DESIGN: Prospective prevalent cohort study. SETTING & PARTICIPANTS: We collected sociodemographic parameters, medical and transplant history, and laboratory data at baseline from 879 prevalent kidney transplant recipients (mean age, 49 ± 13 [standard deviation] years; 58% men; and 17% with diabetes mellitus). PREDICTOR: We assessed HRQoL using the KDQoL-SF (Kidney Disease Quality of Life Short Form) questionnaire and assessed depressive symptoms using the Center for Epidemiologic Studies-Depression Scale. OUTCOMES: All-cause mortality and death-censored transplant loss or death with functioning transplant. Cox regression models and semiparametric competing-risks regression analyses were used to measure associations between HRQoL scores and outcomes. RESULTS: Most examined HRQoL domains were associated with clinical outcome in unadjusted models. After adjusting for several important confounders, the 36-Item Short Form Health Survey (SF-36) Physical Composite Score and Physical Functioning and General Health Perception subscale scores remained independently associated with clinical outcomes. Every 10-point increase in SF-36 Physical Composite Score and Physical Functioning and General Health Perception scores was associated with 18% (HR, 0.82; 95% CI, 0.71-0.95), 11% (HR, 0.89; 95% CI, 0.84-0.94), and 7% lower risks of mortality (HR, 0.93; 95% CI, 0.88-1.00), respectively. LIMITATIONS: Single-center study. CONCLUSIONS: We showed that the SF-36 Physical Composite Score and Physical Functioning and General Health Perception KDQoL-SF domain scores are associated independently with increased risk of mortality in kidney transplant patients. Regular assessment of HRQoL may be a useful tool to inform health care providers about the prognosis of kidney transplant recipients. Additional studies are needed to assess whether interventions aimed at improving HRQoL would improve clinical outcomes in this patient population.

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).

Diagnostic accuracy of serum parathyroid hormone levels in kidney transplant recipients with moderate-to-advanced CKD.

BACKGROUND/AIMS: Elevated parathyroid hormone (PTH) is used to diagnose high turnover bone disease in chronic kidney disease (CKD). The diagnostic accuracy of PTH in kidney transplant recipients with CKD is unknown. METHODS: We examined kidney transplant recipients with CKD stages 3 (n = 498) and 4 (n = 141) to determine the sensitivity and specificity of the Kidney/Dialysis Outcome Quality Initiative (K/DOQI)-recommended PTH levels in detecting elevated serum ß-CrossLaps (CTX) or osteocalcin (OC) levels. We performed receiver-operator curve analyses to determine CKD stage-specific PTH levels that provide optimal diagnostic accuracy. RESULTS: PTH below the lower limits of the K/DOQI ranges (35 and 70 pg/ml in CKD stages 3 and 4, respectively) showed sensitivity of >90% in diagnosing increases in biochemical markers. The upper limits (70 and 110 pg/ml), however, showed poor specificity. A specificity of >90% for detecting increased biochemical markers was seen with PTH of >140 and >240 pg/ml in CKD stages 3 and 4, respectively. CONCLUSION: Currently applied cutoffs for PTH in kidney transplant recipients with CKD stages 3 and 4 do not appear to adequately detect increased biochemical markers of bone turnover. Diagnostic uncertainty exists in patients with CKD stage 3 and PTH between 35 and 140 pg/ml, and CKD stage 4 and PTH between 70 and 240 pg/ml.

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.

Prevalence and associated risk factors of periodic limb movement in sleep in two German population-based studies.

STUDY OBJECTIVES: Periodic limb movements in sleep (PLMS) are frequent motor phenomena; however, population-based data are scarce. We assessed the prevalence of PLMS and factors associated with PLMS within two German population-based cohorts, the SHIP-TREND and BiDirect. METHODS: Single-night polysomnography was performed on 1107 subjects recruited from the general population (mean age: 52.9 years, 54.1% men) in the SHIP-TREND and on 247 participants (mean age: 57.6 years, 50.6% men) in the BiDirect. PLMS were evaluated using the standard criteria of the American Academy of Sleep Medicine. Sociodemographic data, behavioral variables, medical history, current medication, and other sleep disorders were assessed. RESULTS: The prevalence of PLMS index (PLMSI) >15/hour was 32.4% (SHIP-TREND) and 36.4% (BiDirect). In multivariable models, age (odds ratio [OR] = 1.05 per +1 year), male gender (OR = 2.20), restless legs syndrome (OR = 2.32), physical inactivity (OR = 1.52), current smoking (OR = 1.49), diabetes (OR = 2.13), antidepressant use (OR = 2.27), lower serum magnesium (OR per -0.1 mmol/L = 1.27) showed a positive, and the intake of beta-blockers an inverse association with PLMSI >15/hour in SHIP-TREND. In BiDirect, age (OR = 1.13 per +1 year), body mass index (OR = 1.11 per +1 kg/m2), and restless legs syndrome (OR = 8.77) were significantly associated with PLMSI >15/hour. CONCLUSIONS: A high PLMSI is frequent in the German population. Age, male gender, restless legs syndrome, physical inactivity, current smoking, obesity, diabetes, antidepressant use, and lower magnesium were independently associated with PLMSI >15/hour in at least one of the cohorts.

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 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.

Associations between poor sleep quality and different measures of obesity.

OBJECTIVE: Poor sleep may be a risk factor for obesity. Previous studies have mainly investigated the effects of sleep duration on body mass index, but research considering overall sleep quality and other anthropometric measures is scarce. The aim of this study was to examine the association between sleep quality and different measures of obesity (general obesity, abdominal obesity, body composition) in a population-based sample of adults. METHODS: The study included 753 participants aged 35-65 years from the BiDirect Study, conducted in Münster, Germany. Participants completed the Pittsburgh Sleep Quality Index (PSQI) on sleep characteristics. Weight, height, and waist circumference were measured by trained study nurses. Body composition (fat mass and fat-free mass) was assessed using bioelectrical impedance analysis. The cross-sectional relationship between sleep quality and measures of obesity was investigated using logistic regression analysis. RESULTS: Among the participants, 65.3% reported good (PSQI ≤ 5) and 34.7% poor (PSQI > 5) sleep quality. We observed a significant association of poorer sleep quality assessed by the continuous PSQI score with general obesity and high body fat (for both, odds ratio = 1.07, 95% confidence interval = 1.01-1.13), adjusted for socio-demographic and lifestyle factors. Further adjustment for depressive symptoms and somatic comorbidities attenuated the relationship. The observed association was mainly driven by the PSQI components sleep latency, sleep disturbances, and daytime dysfunction. CONCLUSIONS: The present study suggests that poor sleep quality may predict obesity and high body fat mass among adults. However, a causal relationship still has to be confirmed by prospective studies with objective measurements of sleep and obesity.

Serum osteoprotegerin is associated with pulse pressure in kidney transplant recipients.

Pulse pressure (PP) reflects increased large artery stiffness, which is caused, in part, by arterial calcification in patients with chronic kidney disease. PP has been shown to predict both cardiovascular and cerebrovascular events in various patient populations, including kidney transplant (KTX) recipients. Osteoprotegerin (OPG) is a marker and regulator of arterial calcification, and it is related to cardiovascular survival in hemodialysis patients. Here we tested the hypothesis that OPG is associated with increased pulse pressure. We cross-sectionally analyzed the association between serum OPG and PP in a prevalent cohort of 969 KTX patients (mean age: 51 +/- --13 years, 57% male, 21% diabetics, mean eGFR 51 +/- 20 ml/min/1.73 m2). Independent associations were tested in a linear regression model adjusted for multiple covariables. PP was positively correlated with serum OPG (rho = 0.284, p < 0.001). Additionally, a positive correlation was seen between PP versus age (r = 0.358, p < 0.001), the Charlson Comorbidity Index (r = 0.232, p < 0.001), serum glucose (r = 0.172, p < 0.001), BMI (r = 0.133, p = 0.001) and serum cholesterol (r = 0.094, p = 0.003). PP was negatively correlated with serum Ca, albumin and eGFR. The association between PP and OPG remained significant after adjusting for multiple potentially relevant covariables (beta = 0.143, p < 0.001). We conclude that serum OPG is independently associated with pulse pressure in kidney transplant recipients.

Red cell distribution width is associated with mortality in kidney transplant recipients.

BACKGROUND: Red cell distribution width (RDW), a parameter routinely reported as part of the complete blood count, is associated with increased morbidity and mortality risk in different patient populations. No published data are available about the association between RDW and mortality in kidney transplant recipients. METHODS: We collected socio-demographic, clinical parameters, medical and transplant history and laboratory data at baseline in 723 prevalent kidney transplant recipients between June and October 2008 [mean age 51 ± 13 (SD) years, 56 % men, 21 % diabetics]. Associations between baseline RDW values and all-cause mortality over 3 years were examined in unadjusted and adjusted models. RESULTS: Increasing RDW was associated with increased mortality in both unadjusted [(HR(1 % increase) = 1.63; 95 % CI 1.41-1.89) and (HR(>median) = 2.74; 95 % CI 1.68-4.48)] and fully adjusted models [(HR(1 % increase) = 1.60; 95 % CI 1.27-1.89) and (HR(>median) = 1.33; 95 % CI 0.76-2.35)]. In reclassification analyses, RDW improved the predictive value of all-cause mortality prediction models [the net reclassification improvement (NRI) was 0.189; p < 0.001]. CONCLUSIONS: RDW, a cheap and readily available but largely neglected parameter independently, predicts mortality in prevalent kidney transplant recipients and could potentially been used in everyday risk assessment of kidney transplant recipients.

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.

Serum adiponectin levels and mortality after kidney transplantation.

BACKGROUND AND OBJECTIVES: Adiponectin (ADPN), an adipose tissue-derived hormone, has protective properties with respect to atherogenesis, inflammation, and energy homeostasis. Its beneficial role has not been consistent in patients with CKD or those undergoing dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study examined the association of plasma ADPN levels in 987 prevalent kidney transplant recipients (mean age ± SD, 51.0±12.8 years; estimated GFR, 52.8±21.9 ml/min per 1.73 m(2); median time since transplant, 78 months) on all-cause mortality and death-censored graft failure. Patients were enrolled between February and August 2007 and were followed for a median of 51 months (interquartile range, 49-53 months). Using Cox proportional hazard models, the association of log-transformed plasma adiponectin was studied, with and without adjustment for demographic variables, baseline GFR, markers of inflammation, and cardiovascular risk factors. RESULTS: At baseline, patients in the lowest ADPN tertile were significantly more likely to be male; to be smokers; to have a higher baseline GFR, lower systolic BP, and lower HDL cholesterol level; and to have higher body mass index, abdominal circumference, C-reactive protein level, and total cholesterol level. The adjusted hazard ratio for death with elevated plasma ADPN (per natural log) was 1.44, and there was no significant interaction with any relevant cardiovascular risk subgroups (i.e., advanced age; diabetes; or elevated body mass index, waist circumference, C-reactive protein, or Framingham risk score). The hazard for death-censored graft failure was nonsignificant at 1.03. CONCLUSION: Elevated ADPN levels are associated with higher risk for death but not allograft failure in prevalent kidney transplant recipients.