Katalin Fornadi

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.

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.

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).

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 of Restless Legs Syndrome With Incident Parkinson’s Disease

Study Objectives: The association between restless legs syndrome (RLS) and Parkinsons 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 m2/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 m2/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.

Cardio- and cerebrovascular risk is associated with decreased slow wave sleep in patients with chronic kidney disease

WCN 2013 No: 1259 Topic: 36 — Other Topic Cardioand cerebrovascular risk is associated with decreased slow wave sleep in patients with chronic kidney disease A.V. Lindner, K. Ronai, K. Fornadi, A.S. Lazar, M.E. Czira, A. Dunai, R. Zoller, O. Veber, A. Szentkiralyi, Z. Kiss, E. Toronyi, M.Z. Molnar, I. Mucsi, M. Novak. Department of Neurology, Semmelweis University, Budapest, Hungary; Institute of Behavioural Sciences, Semmelweis University, Budapest, Hungary; Amgen Hungary Limited, Semmelweis University, Budapest, Hungary; Dept. of Transplantation and Surgery, Semmelweis University, Budapest, Hungary; Division of Nephrology, University of Toronto, Toronto, ON, Canada; Los Angeles Biomedical Research Institute at Harbor, UCLA, Torrance, CA, USA; Institute of Pathophysiology, Semmelweis University, Budapest, Hungary; Division of Nephrology, McGill University, Montreal, QC, Canada; Dept. of Psychiatry, University of Toronto, Toronto, ON, Canada Background: Previous studies reported that sleep fragmentation and decreased slow wave sleep related to certain cardiovascular risk factors e.g. cholesterol levels, obesity in general population. Objective: Our study aims to analyze association between cardioand cerebrovascular risk and slow wave sleep in patients with chronic kidney disease. Patients and methods: 100 kidney transplanted and 50 wait-listed hemodialyzed patients underwent polysomnography. The ten-year coronary heart disease risk was estimated for all patients using the Framingham Score. Moreover, the ten-year estimated risk of stroke was calculated according to the modified version of the Framingham Stroke Risk Profile. In multivariate linear regression models logarithmic transformed Framingham scores were used for estimating association between slow wave sleep and cardiocerebrovascular risk. Results: Mean age was 51 ± 13 yrs, ratio of males was 56% in the population. Slow wave sleep was reverse related to cardiovascular and stroke risk (Spearmans rho: 0.259, p = 0.003; −0.209, p = 0.011). In multivariate linear regression models the lower ratio of slow wave sleep was independently associated with the logarithmic transformed Framingham cardiovascular (beta =−0.211; 95% CI: −0.45 to −007) and cerebrovascular scores (beta =−0.155; 95% CI: −0.033–0.0) after adjusting for important co-variables (apnea–hypopnea index, serum albumin and hemoglobin levels, type of renal replacement, Charlson comorbidity index, sleep efficiency). Conclusion: Decreased slow wave sleep was found to be an independent predictor of higher cardioand cerebrovascular risk score in patients with chronic kidney disease. doi:10.1016/j.jns.2013.07.2299 Abstract — WCN 2013 No: 673 Topic: 36 — Other Topic Is transient global amnesia (TGA) hereditary? WCN 2013 No: 673 Topic: 36 — Other Topic Is transient global amnesia (TGA) hereditary? M.M. Dupuis, F. Evrard, S. De Bruijn, J. Segers-van Rijn, F. Dupuis, P. Jacquerye, G. Picard, O. Ghysens, K. Dahan, C. Verellen. Clinique St Pierre, Ottignies, Belgium; Neurology, Hagaziekenhuis, Den Haag, The Netherlands; Institut de Pathologie et de Genetique,