Anett Lindner

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 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 (Spearmans 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.

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.

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 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.

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.

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 β regression coefficient (β)=-0.362, P=0.043] and higher night/day LF/HF ratio (β=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.

[Restless legs syndrome: the most prevalent "unknown" disorder].

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.

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 (β=0.263; CI: 0.026-0.500) and REM beta activity (β=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.