Associations between bioelectrical impedance analysis-derived phase angle, protein-energy wasting and all-cause mortality in older patients undergoing haemodialysis.

AIM: Protein-energy wasting (PEW) is a common syndrome in patients undergoing haemodialysis (HD) and is associated with poor prognosis. Bioelectrical impedance analysis (BIA)-derived phase angle (PA) is useful for predicting PEW, but sex and age need to be considered. We aimed to reveal sex-specific cut-off values of PA predicting PEW in HD patients aged ≥65. METHODS: This two-centre retrospective cohort study included patients on HD who underwent BIA. PEW was detected using the International Society of Renal Nutrition and Metabolism (ISRNM) criteria as a reference. The PA was measured using a multifrequency bioimpedance device. Sex-specific cut-off values of PA predicting PEW were detected by receiver-operator characteristic analysis. We investigated the association between PEW determined using sex-specific cut-off values for PA and all-cause mortality. RESULTS: This study included 274 patients undergoing HD, with a median age of 75 (70-80) years, mean PA of 3.8 ± 1.1° and PEW of 43%. Over a median follow-up duration of 1095 (400-1095) days, 111 patients died. Cut-off values of PA predicting PEW were as follows: female, 3.00° (sensitivity, 87.3%; specificity, 77.5%), and male, 3.84° (sensitivity, 77.6%; specificity, 71.4%). The kappa coefficient between sex-specific cut-off values of the PA and ISRNM criteria had a moderate coincidence level of 0.55. PEW detected by PA was independently associated with all-cause mortality (hazard ratio: 2.40; 95% confidence interval: 1.51-3.85; p < .001). CONCLUSIONS: Sex-specific cut-off values for PA in older HD patients may be useful as a screening tool for predicting PEW and mortality.

Criteria for classification of protein-energy wasting in dialysis patients: impact on prevalence.

Malnutrition is highly prevalent in dialysis patients and associated with poor outcomes. In 2008, protein-energy wasting (PEW) was coined by the International Society of Renal Nutrition and Metabolism (ISRNM), as a single pathological condition in which undernourishment and hypercatabolism converge. In 2014, a new simplified score was described using serum creatinine adjusted for body surface area (sCr/BSA) to replace a reduction of muscle mass over time in the muscle wasting category. We have now compared PEW-ISRNM 2008 and PEW-score 2014 to evaluate the prevalence of PEW and the risk of death in 109 haemodialysis patients. This was a retrospective analysis of cross sectional data with a median prospective follow-up of 20 months. The prevalence of PEW was 41 % for PEW-ISRNM 2008 and 63 % for PEW-score 2014 (P <0·002). Using PEW-score 2014: twenty-nine patients (27 %) had severe malnutrition (PEW-score 2014 0-1) and forty (37 %) with moderate malnutrition (score 2). Additionally, thirty-three (30 %) patients had mild wasting and only seven patients (6 %) presented a normal nutritional status. sCr/BSA correlated with lean total mass (R 0·46. P<0·001). A diagnosis of PEW according to PEW-score 2014, but not according to PEW-ISRNM 2008, was significantly associated with short-term mortality (P=0·0349) in univariate but not in multivariate analysis (P=0·069). In conclusion, the new PEW-score 2014 incorporating sCr/BSA identifies a higher number of dialysis PEW patients than PEW-ISRNM 2008. Whereas PEW-score-2014 provides timelier and therefore more clinically relevant information, its association with early mortality needs to be confirmed in larger studies.

Evaluating haemodialysis patient's nutritional status: Body mass index or body cell mass index?

OBJECTIVE: Evaluate which of two combinations of parameters based on International Society of Renal Nutrition and Metabolism recommendations could better identify patients with protein-energy wasting (PEW) and to compare the relationship of these two combinations with other clinical and body composition parameters. METHODS: This was a multicentre longitudinal study with 24 months of follow-up. The PEW patients were characterized by: Group A (GA ) - normalized protein catabolic rate (nPCR) < 1.0 g/kg per day, albumin <3.8 g/dL and body cell mass index (BCMI) < 6.4 kg/m2 (n = 203); Group B (GB ) - nPCR <1.0 g/kg per day, albumin <3.8 g/dL and body mass index (BMI) <23 kg/m2 (n = 109). All the patients who did not meet these requirements were considered "well-nourished" (GA : n = 1818; GB : n = 3292). RESULTS: When compared to the well-nourished patients, PEW patients in the GA presented higher age, Kt/V, C-reactive protein, relative overhydration, fat tissue index (FTI); lower creatinine, albumin, nPCR, PTH, haemoglobin, phosphorus, calcium X phosphorus product, potassium, dry weight, BMI, BCMI, lean tissue index, %IDWG . In the GB , well-nourished patients FTI was significantly higher. In Cox analysis, the combination with BCMI was a strong independent predictor of mortality in these patients (hazard ratio: 1.48; confidence interval: 1.00-2.19; P = 0.048), even after adjustment. Although GB combination seemed to be also a predictor of death (hazard ratio: 2.67; confidence interval: 1.92-3.71; P < 0.001), when adjusted, the association remained no longer significant. CONCLUSION: A new combination of parameters including protein intake, albumin and BCMI demonstrated significant associations with other nutrition and inflammation parameters as well as with mortality.

[Percutaneous endoscopic gastrostomy in geriatrics : Indications, technique and complications]. / Die perkutane endoskopische Gastrostomie in der Altersmedizin : Indikationen, Technik und Komplikationen.

The technique of percutaneous endoscopic gastrostomy (PEG) was introduced in 1979 as a semi-invasive approach for children with the need for a gastric fistula in order to avoid an operative intervention. The suture pull-through method was rapidly established and is now omnipresent. Because scientific evidence is broadly missing, there is some uncertainty about the indications in geriatric medicine. Guidelines do not recommend the insertion of a PEG in patients with severe dementia and malnutrition. Tube feeding is mainly recommended as a temporary method for patients who cannot take oral nutrition for more than 3 days or for whom the energy intake for more than 10 days presumably covers less than 50% of their needs, assuming that the overall prognosis is reasonable. Insertion of a PEG is only recommended if artificial nutrition is expected to be necessary for more than 3-4 weeks or if a nasogastric tube is not tolerated.

Diagnosis and prevalence of protein-energy wasting and its association with mortality in Japanese haemodialysis patients.

AIM: The International Society of Renal Nutrition and Metabolism (ISRNM) has proposed the diagnostic criteria for protein-energy wasting (PEW). We studied Japanese haemodialysis (HD) patients to verify the diagnostic method, especially with respect to the body mass index (BMI) criterion, as well as the prevalence of PEW and its association with mortality. METHODS: Japanese patients receiving maintenance HD at three outpatient clinics in Tokyo (n = 210) were enrolled, and prospectively followed-up for 3 years. PEW was diagnosed at baseline, according to the four categories (serum chemistry, body mass, muscle mass and dietary intake) recommended by the ISRNM. For the category of body mass, we select a body mass index (BMI) and set up three thresholds, <18.5, <20.0 and <23.0 kg/m2 , as the diagnostic criterion. The patients who satisfied at least three out of the four categories were diagnosed as PEW. RESULTS: Protein-energy wasting, when the threshold of a BMI among the diagnostic criteria was defined as <18.5 kg/m2 , was recognized as an independent risk factor for mortality. However, PEW was not recognized as a risk factor when the BMI diagnostic criterion was set at <20.0 or <23.0 kg/m2 . Overall, 14.8% of the patients had PEW. The survival rate of PEW patients was significantly lower than that of non-PEW patients (log rank, P < 0.001). CONCLUSIONS: The diagnosis algorithm of PEW proposed by an expert panel of the ISRNM strongly associates with mortality. However, given differences in body size in Japan, we suggest to revise the BMI criterion from <23.0 kg/m2 to <18.5 kg/m2 .

Comparison of Nutritional Risk Scores for Predicting Mortality in Japanese Chronic Hemodialysis Patients.

OBJECTIVE: Protein energy wasting (PEW) is consistently associated with poor prognosis in hemodialysis (HD) patients. We compared the predictability of PEW as diagnosed by The International Society of Renal Nutrition and Metabolism criteria (PEWISRNM) and geriatric nutritional risk index (GNRI) for all-cause mortality in Japanese HD patients. As cut-off values for body mass index (BMI) for PEW have not been established in PEWISRNM for Asian populations, these were also investigated. DESIGN AND SUBJECTS: The nutritional status from 409 HD patients was evaluated according to ISRNM and GNRI criteria. To compare the predictability of mortality, C-index, net reclassification improvement (NRI) and integrated discrimination improvement were evaluated. RESULTS: During follow-up (median, 52 months; range, 7 months), 70 patients (17.1%) presented PEW according to ISRNM and 131 patients (32.1%) according to GNRI; in addition, 101 patients (24.7%) died. PEWISRNM and GNRI were identified as independent predictors of death. Addition of PEWISRNM and GNRI to a predictive model based on established risk factors improved NRI and integrated discrimination improvement. However, no differences were found between models including PEWISRNM and GNRI. When lowering the criterion level of BMI per 1 kg/m2 sequentially, PEWISRNM at BMI <20 kg/m2 maximized the hazard ratio for mortality. The model including PEWISRNM at BMI <20 kg/m2 improved NRI compared with the model including GNRI. CONCLUSION: PEWISRNM and GNRI represent independent predictors of mortality, with comparable predictability. The diagnostic criterion of BMI in the ISRNM for Japanese population might be better at <20 kg/m2 than at <23 kg/m2.

Antibiotics as part of the management of severe acute malnutrition.

BACKGROUND: Severe acute malnutrition contributes to 1 million deaths among children annually. Adding routine antibiotic agents to nutritional therapy may increase recovery rates and decrease mortality among children with severe acute malnutrition treated in the community. METHODS: In this randomized, double-blind, placebo-controlled trial, we randomly assigned Malawian children, 6 to 59 months of age, with severe acute malnutrition to receive amoxicillin, cefdinir, or placebo for 7 days in addition to ready-to-use therapeutic food for the outpatient treatment of uncomplicated severe acute malnutrition. The primary outcomes were the rate of nutritional recovery and the mortality rate. RESULTS: A total of 2767 children with severe acute malnutrition were enrolled. In the amoxicillin, cefdinir, and placebo groups, 88.7%, 90.9%, and 85.1% of the children recovered, respectively (relative risk of treatment failure with placebo vs. amoxicillin, 1.32; 95% confidence interval [CI], 1.04 to 1.68; relative risk with placebo vs. cefdinir, 1.64; 95% CI, 1.27 to 2.11). The mortality rates for the three groups were 4.8%, 4.1%, and 7.4%, respectively (relative risk of death with placebo vs. amoxicillin, 1.55; 95% CI, 1.07 to 2.24; relative risk with placebo vs. cefdinir, 1.80; 95% CI, 1.22 to 2.64). Among children who recovered, the rate of weight gain was increased among those who received antibiotics. No interaction between type of severe acute malnutrition and intervention group was observed for either the rate of nutritional recovery or the mortality rate. CONCLUSIONS: The addition of antibiotics to therapeutic regimens for uncomplicated severe acute malnutrition was associated with a significant improvement in recovery and mortality rates. (Funded by the Hickey Family Foundation and others; ClinicalTrials.gov number, NCT01000298.).

Metabolomic Changes in Serum of Children with Different Clinical Diagnoses of Malnutrition.

BACKGROUND: Mortality in children with severe acute malnutrition (SAM) remains high despite standardized rehabilitation protocols. Two forms of SAM are classically distinguished: kwashiorkor and marasmus. Children with kwashiorkor have nutritional edema and metabolic disturbances, including hypoalbuminemia and hepatic steatosis, whereas marasmus is characterized by severe wasting. The metabolic changes underlying these phenotypes have been poorly characterized, and whether homeostasis is achieved during hospital stay is unclear. OBJECTIVES: We aimed to characterize metabolic differences between children with marasmus and kwashiorkor at hospital admission and after clinical stabilization and to compare them with stunted and nonstunted community controls. METHODS: We studied children aged 9-59 mo from Malawi who were hospitalized with SAM (n = 40; 21 with kwashiorkor and 19 with marasmus) or living in the community (n = 157; 78 stunted and 79 nonstunted). Serum from patients with SAM was obtained at hospital admission and 3 d after nutritional stabilization and from community controls. With the use of targeted metabolomics, 141 metabolites, including amino acids, biogenic amines, acylcarnitines, sphingomyelins, and phosphatidylcholines, were measured. RESULTS: At admission, most metabolites (128 of 141; 91%) were lower in children with kwashiorkor than in those with marasmus, with significant differences in several amino acids and biogenic amines, including those of the kynurenine-tryptophan pathway. Several phosphatidylcholines and some acylcarnitines also differed. Patients with SAM had profiles that were profoundly different from those of stunted and nonstunted controls, even after clinical stabilization. Amino acids and biogenic amines generally improved with nutritional rehabilitation, but most sphingomyelins and phosphatidylcholines did not. CONCLUSIONS: Children with kwashiorkor were metabolically distinct from those with marasmus, and were more prone to severe metabolic disruptions. Children with SAM showed metabolic profiles that were profoundly different from stunted and nonstunted controls, even after clinical stabilization. Therefore, metabolic recovery in children with SAM likely extends beyond discharge, which may explain the poor long-term outcomes in these children. This trial was registered at isrctn.org as ISRCTN13916953.

Serum hepatocyte growth factor is associated with truncal fat mass and increased mortality in chronic kidney disease stage 5 patients with protein-energy wasting.

BACKGROUND: Obese sarcopenia characterized by increased fat mass and protein-energy wasting (PEW) is not uncommon in chronic kidney disease (CKD) stage 5 patients in whom it is associated with worse outcomes. Serum hepatocyte growth factor (HGF) is associated with obesity in the general population and is increased in CKD patients in whom its association with body composition is not known. We studied the associations between HGF, PEW and body composition, and between HGF and mortality, in CKD stage 5 patients starting dialysis. METHODS: In 224 CKD stage 5 patients (139 males, mean age 52 years, mean glomerular filtration rate (GFR) 6.6 mL/min), blood samples were obtained for analyses of HGF, high-sensitivity C-reactive protein (hsCRP), glucose, insulin and lipids. Total fat mass index (FMI), truncal fat mass index (TFMI) and lean body mass index (LBMI) assessed by dual-energy X-ray absorptiometry and PEW assessed by subjective global assessment (SGA) were recorded at baseline. Patients were followed up for 5 years. RESULTS: Serum HGF levels were higher in patients with high TFMI versus low TFMI [3.1 (IQR: 2.4-4.5) versus 2.7 (IQR: 1.9-3.8) ng/mL; P = 0.01] and in those with PEW versus non-PEW [3.4 (IQR: 2.4-3.6) versus 2.8 (IQR: 2.1-3.8) ng/mL; P = 0.03]. Patients with both high TFMI and presence of PEW had significantly (P < 0.001) higher HGF concentration [4.4 (IQR: 3.3-6.6) ng/mL] than other patient groups (high TFMI and non-PEW, low TFMI and PEW or low TFMI and non-PEW). Multivariate linear regression showed that TFMI was an independent predictor of HGF (R(2) = 0.21, P = 0.048). In Cox analysis, patients with high HGF and presence of PEW had worse all-cause mortality after adjusting for age, gender and hsCRP (HR: 3.59, 95% CI: 1.19-5.35). CONCLUSIONS: Increased TFMI was an independent predictor of HGF in CKD stage 5 patients. Moreover, an elevated HGF level increased the mortality risk in the presence of PEW. These results suggest a central role of HGF in the metabolic and nutritional alterations in CKD stage 5 patients.

Lower plasma visceral protein concentrations are independently associated with higher mortality in patients on peritoneal dialysis.

Protein-energy wasting (PEW) is strongly associated with high mortality in continuous ambulatory peritoneal dialysis (CAPD) patients. However, its clinical assessment has not been well defined. The aim of the present study was to investigate the relationship between combined nutritional indicators and mortality in CAPD patients. In the present retrospective cohort study, a total of 885 incident CAPD patients were enrolled. Nutritional status at the initiation of CAPD was assessed by BMI and biochemical indices (serum albumin, prealbumin, transferrin, creatinine and total cholesterol). The primary outcome was all-cause mortality. Principal components factor analysis was used to identify the combined nutritional parameters. Their association with mortality was examined by multivariable-adjusted Cox models. The mean age was 47·4 (SD 14·8) years, 59·2 % (n 524) were male and 24·6 % (n 218) were diabetic. Of the total patients, 130 (14·7 %) had BMI < 18·5 kg/m², 439 (49·6 %) had albumin < 38 g/l ( < 3·8 g/dl), 303 (34·2 %) had prealbumin < 300 mg/l ( < 30 mg/dl), 404 (45·6 %) had transferrin < 2 g/l ( < 200 mg/dl), 501 (56·6 %) had total cholesterol < 5·2 mmol/l ( < 200 mg/dl) and 466 (52·7 %) had creatinine < 707 µmol/l ( < 8 mg/dl). Overall, three components such as visceral proteins, muscle-mass surrogate and BMI were extracted, which explained 69·95 % of the total variance of the nutritional parameters. After adjusting for demographic variables, co-morbid conditions, Hb, TAG and high-sensitivity C-reactive protein, the factor score of visceral proteins including albumin, prealbumin and transferrin was independently associated with mortality (hazard ratio 0·73, 95 % CI 0·60, 0·89; P= 0·002). Lower visceral protein concentrations may be independently associated with higher mortality in incident CAPD patients. Simultaneous measurements of serum albumin, prealbumin and transferrin could be helpful to monitor PEW.

Comparison of weight-for-height and mid-upper arm circumference (MUAC) in a therapeutic feeding programme in South Sudan: is MUAC alone a sufficient criterion for admission of children at high risk of mortality?

OBJECTIVE: The present study was performed to describe the operational implications of using mid-upper arm circumference (MUAC) as a single admission criterion for treatment of severe acute malnutrition in South Sudan. DESIGN: We performed a retrospective analysis of routine programme data of children with severe acute malnutrition aged 6-59 months admitted to a therapeutic feeding programme using weight-for-height Z-score (WHZ) and/or MUAC. To understand the implications of using MUAC as a single admission criterion, we compared patient characteristics and treatment outcomes for children admitted with MUAC<115 mm (irrespective of WHZ) v. children admitted with WHZ<-3 and MUAC≥115 mm. RESULTS: Of 2205 children included for analysis, 719 (32·6 %) were admitted to the programme with MUAC<115 mm and 1486 (67·4 %) with WHZ<-3 and MUAC≥115 mm. Children who would have been admitted using a single MUAC<115 mm criterion were more severely malnourished and more likely to be female and younger. Compared with children admitted with WHZ<-3 and MUAC≥115 mm, children who would have been admitted using MUAC<115 mm were less likely to recover (54 % v. 69 %) and had higher risk of death (4 % v. 1 %), but responded to treatment with greater weight and MUAC gains. MUAC<115 mm would have failed to identify 33 % of deaths, while 98 % were identified by WHZ<-3 alone and 100 % by MUAC<130 mm. CONCLUSIONS: The study shows that MUAC<115 mm identified more severely malnourished children with a higher risk of mortality but failed to identify a third of the children who died. Admission criteria for therapeutic feeding should be adapted to the programmatic context with consideration for both operational and public health implications.

Severe malnutrition among children under the age of 5 years admitted to a rural district hospital in southern Mozambique.

OBJECTIVE: To describe the burden, clinical characteristics and prognostic factors of severe malnutrition in children under the age of 5 years. DESIGN: Retrospective study of hospital-based data systematically collected from January 2001 to December 2010. SETTING: Rural Mozambican district hospital. SUBJECTS: All children aged <5 years admitted with severe malnutrition. RESULTS: During the 10-year long study surveillance, 274 813 children belonging to Manhiça's Demographic Surveillance System were seen at out-patient clinics, almost half of whom (47 %) presented with some indication of malnutrition and 6% (17 188/274 813) with severe malnutrition. Of these, only 15% (2522/17 188) were eventually admitted. Case fatality rate of severe malnutrition was 7% (162/2274). Bacteraemia, hypoglycaemia, oral candidiasis, prostration, oedema, pallor and acute diarrhoea were independently associated with an increased risk of in-hospital mortality, while malaria parasitaemia and breast-feeding were independently associated with a lower risk of a poor outcome. Overall minimum communitybased incidence rate was 15 cases per 1000 child-years at risk and children aged 12­23 months had the highest incidence. CONCLUSIONS: Severe malnutrition among admitted children in this Mozambican setting was common but frequently went undetected, despite being associated with a high risk of death. Measures to improve its recognition by clinicians responsible for the first evaluation of patients at the out-patient level are urgently needed so as to improve their likelihood of survival. Together with this, the rapid management of complications such as hypoglycaemia and concomitant co-infections such as bacteraemia, acute diarrhoea, oral candidiasis and HIV/AIDS may contribute to reverse the intolerable toll that malnutrition poses in the health of children in rural African settings.

Under-five protein energy malnutrition admitted at the University of Nigeria Teaching Hospital, Enugu: a 10 year retrospective review.

OBJECTIVE: To determine the prevalence, risk factors, co-morbidities and case fatality rates of Protein Energy Malnutrition (PEM) admissions at the paediatric ward of the University of Nigeria Teaching Hospital Enugu, South-east Nigeria over a 10 year period. DESIGN: A retrospective study using case Notes, admission and mortality registers retrieved from the Hospital's Medical Records Department. SUBJECTS: All children aged 0 to 59 months admitted into the hospital on account of PEM between 1996 and 2005. RESULTS: A total of 212 children with PEM were admitted during the period under review comprising of 127 (59.9%) males and 85 (40.1%) females. The most common age groups with PEM were 6 to 12 months (55.7%) and 13 to 24 months (36.8%). Marasmus (34.9%) was the most common form of PEM noted in this review. Diarrhea and malaria were the most common associated co-morbidities. Majority (64.9%) of the patients were from the lower socio-economic class. The overall case fatality rate was 40.1% which was slightly higher among males (50.9%). Mortality in those with marasmic-kwashiokor and in the unclassified group was 53.3% and 54.5% respectively. CONCLUSION: Most of the admissions and case fatality were noted in those aged 6 to 24 months which coincides with the weaning period. Marasmic-kwashiokor is associated with higher case fatality rate than other forms of PEM. We suggest strengthening of the infant feeding practices by promoting exclusive breastfeeding for the first six months of life, followed by appropriate weaning with continued breast feeding. Under-five children should be screened for PEM at the community level for early diagnosis and prompt management as a way of reducing the high mortality associated with admitted severe cases.

Nutritional status and clinical outcome of children on continuous renal replacement therapy: a prospective observational study.

BACKGROUND: No studies on continuous renal replacement therapy (CRRT) have analyzed nutritional status in children. The objective of this study was to assess the association between mortality and nutritional status of children receiving CRRT. METHODS: Prospective observational study to analyze the nutritional status of children receiving CRRT and its association with mortality. The variables recorded were age, weight, sex, diagnosis, albumin, creatinine, urea, uric acid, severity of illness scores, CRRT-related complications, duration of admission to the pediatric intensive care unit, and mortality. RESULTS: The sample comprised 174 critically ill children on CRRT. The median weight of the patients was 10 kg, 35% were under percentile (P) 3, and 56% had a weight/P50 ratio of less than 0.85. Only two patients were above P95. The mean age for patients under P3 was significantly lower than that of the other patients (p = 0.03). The incidence of weight under P3 was greater in younger children (p = 0.007) and in cardiac patients and in those who had previous chronic renal insufficiency (p = 0.047). The mortality analysis did not include patients with pre-existing renal disease. Mortality was 38.9%. Mortality for patients with weight < P3 was greater than that of children with weight > P3 (51% vs 33%; p = 0.037). In the univariate and multivariate logistic regression analyses, the only factor associated with mortality was protein-energy wasting (malnutrition) (OR, 2.11; 95% CI, 1.067-4.173; p = 0.032). CONCLUSIONS: The frequency of protein-energy wasting in children who require CRRT is high, and the frequency of obesity is low. Protein-energy wasting is more frequent in children with previous end-stage renal disease and heart disease. Underweight children present a higher mortality rate than patients with normal body weight.

Examining associations of circulating endotoxin with nutritional status, inflammation, and mortality in hemodialysis patients.

OBJECTIVE: Lipopolysaccharide or endotoxin constitutes most part of the outer portion of the cell wall in the gram-negative bacteria. Subclinical endotoxemia could contribute to increased inflammation and mortality in hemodialysis (HD) patients. Endotoxin level and clinical effect are determined by its soluble receptor sCD14 and high-density lipoprotein. We examine the hypothesis that endotoxin level correlates with mortality. METHODS: In this cohort study, endotoxin levels were measured in 306 long-term HD patients who were then followed up for a maximum of 42 months. Soluble CD14 and cytokines levels were also measured. RESULTS: The mean (±SD) endotoxin level was 2.31 ± 3.10 EU/mL (minimum: 0.26 EU/mL, maximum: 22.94 EU/mL, interquartile range: 1.33 EU/mL, median: 1.27 EU/mL). Endotoxin correlated with C-reactive protein (r = 0.11, P < .04). On multivariate logistic regression analysis, high body mass index and low high-density lipoprotein (HDL) cholesterol levels were associated with higher endotoxemia (endotoxin below or above of median). In multivariate Cox regression analysis adjusted for case-mix and nutritional/inflammatory confounders, endotoxin levels in the third quartile versus first quartile were associated with a trend toward increased hazard ratio for death (hazard ratio: 1.83, 95% confidence interval: 0.93 to 3.6, P = .08). CONCLUSIONS: In this HD cohort, we found associations between endotoxemia and C-reactive protein, body composition, and HDL. Moderately high endotoxin levels tended to correlate with increased mortality than the highest circulating endotoxin level. Additional studies are required to assess the effect of endotoxemia on mortality in dialysis population.

Is ghrelin a biomarker for mortality in end-stage renal disease?

Ghrelin is involved in the pathogenesis of protein-energy wasting (PEW), inflammation, and cardiovascular complications in end-stage renal disease (ESRD). Plasma ghrelin may prove to be a powerful biomarker of mortality in ESRD but should be considered in the context of assay specificity, other weight-regulating hormones, nutritional status, systemic inflammation, and cardiovascular risk factors. ESRD patients with PEW, systemic inflammation, and low ghrelin and high leptin concentrations have the highest mortality risk and may benefit the most from ghrelin therapy.

Protein-energy wasting modifies the association of ghrelin with inflammation, leptin, and mortality in hemodialysis patients.

Ghrelin abnormalities contribute to anorexia, inflammation, and cardiovascular risk in hemodialysis patients, leading to worse outcome. However, ghrelin levels are influenced by the nutritional status of the individual. We hypothesized that the consequences of ghrelin alterations in hemodialysis patients are context sensitive and dependent on the presence of protein-energy wasting (PEW). In this cross-sectional study of 217 prevalent hemodialysis patients followed for 31 months, we measured ghrelin, leptin, PEW (subjective global assessment), and C-reactive protein (an index of inflammation). Compared to patients in the middle and upper tertile of ghrelin levels, those in the lowest tertile were older, had higher leptin levels and body mass index, and presented an increased mortality risk that persisted after adjustment for age, gender, and dialysis vintage. This risk was lost after correction for comorbidities. Patients with PEW and low ghrelin values had abnormally high C-reactive protein and leptin by multivariate analysis of variance, and the highest mortality risk compared to non-PEW with high ghrelin from all-cause and cardiovascular-related mortality (adjusted hazard ratios of 3.34 and 3.54, respectively). Low ghrelin values in protein-energy wasted hemodialysis patients were linked to a markedly increased cardiovascular mortality risk. Thus, since these patients were more anorectic, our results provide a clinical scenario where ghrelin therapies may be particularly useful.

Impaired glucose absorption in children with severe malnutrition.

OBJECTIVE: To quantify intestinal glucose absorption in children with two types of severe malnutrition, kwashiorkor and marasmus, compared with healthy children. STUDY DESIGN: Children with kwashiorkor (n = 6) and marasmus (n = 9) and control subjects (n = 3) received a primed (13 mg/kg), constant infusion (0.15 mg/kg/min) of [6,6H2]glucose for 4.5 hours. Two hours after start of the infusion an oral bolus of glucose 1.75 g/kg labeled with [U-13C]glucose 10 mg/g was given and was followed by periodic blood sampling. Mathematical modeling was applied to determine oral glucose absorption. RESULTS: Median total glucose absorption was 5.9 mmol/kg, interquartile range (IQR) 4.5-6.7 mmol/kg and 4.4 (IQR 2.9-5.9) mmol/kg in children with kwashiorkor and marasmus compared with 7.7 (IQR 5.8-9.0) mmol/kg in control subjects; P = .03 compared with marasmus). Children with the lowest glucose absorption were found specifically in the kwashiorkor group and marasmic children with hypoalbuminemia. Severe impairment in absorption correlated with urinary 8-hydroxydeoxyguanosine secretion (r = -0.62, P = .01). CONCLUSIONS: Severe malnutrition is associated with an impaired glucose absorption and decreased glucose absorption correlates with oxidative stress in these children.

Premorbid nutrition and short term outcome of stroke: a multicentre study from India.

BACKGROUND: Little is known about the impact of premorbid undernutrition on stroke outcome in developing countries. AIM: To study the impact of premorbid undernutrition status, measured by the Subjective Global Assessment (SGA) tool, on short term stroke outcome. METHODS: First ever stroke patients admitted to six major hospitals in North and South India participated in this study from 1 March 2008 to 30 September 2009. The SGA tool was administered within 48 h of stroke onset, and 6 months premorbid nutritional status was rated as well nourished (A rating) and undernourished (B and C ratings) using this tool. Stroke outcome was assessed after 30 days using the modified Rankin scale (mRs), and a mRs score >3 was defined as a poor outcome. Statistical analyses were performed using SPSS Statistics V.17.0. RESULTS: Of 477 patients enrolled, 448 patients were included in the analyses. Mean age was 58.1±13.7 years (range 16-96) and 281 (62.7%) patients were men. At admission, premorbid undernutrition was found in 121 (27.2%) patients. Older age (OR 4.99, CI 1.26 to 19.64, p=0.021), hypertension (OR 1.99, CI 1.04 to 3.79, p=0.037) and patients from Andhra Pradesh State (OR 1.87, CI 1.05 to 3.32, p=0.032) were predictors of undernutrition in multiple logistic regression analysis. Premorbid undernutrition (OR 1.99, CI 1.20 to 3.31, p=0.007) and length of hospital stay (OR 3.41, CI 1.91 to 6.06, p<0.0001) were the independent predictors of poor outcome in the multiple logistic regression model. CONCLUSIONS: High rates of premorbid undernutrition in stroke patients were found. Age, hypertension and patients from Andhra Pradesh State were predictors of premorbid undernutrition. Premorbid undernutrition was associated with poor stroke outcome. The results provide opportunities for primary prevention and improving stroke outcome.