Vitamin D in dysphagic patients who have undergone endoscopic gastrostomy for long-term enteral feeding.

OBJECTIVE: Vitamin D plays a major role in biological processes. Its deficiency is associated with increased morbidity and mortality. Patients who have undergone endoscopic gastrostomy (PEG) present with protein-energy malnutrition, and may be at risk for Vitamin D deficiency, due to their age, less sunlight exposure and lower dietary intake. We aimed to determine the prevalence of hypovitaminosis D in PEG-patients, its change under PEG-feeding, and its relationship with serum proteins and risk factors for Vitamin D deficiency. METHODS: This was a prospective observational study, over 4 weeks, after gastrostomy. Data were collected at the initial PEG procedure (T0), and after 4 weeks (T1). Initial evaluation included age, gender, underlying disorder, NRS-2002, BMI, serum albumin, transferrin and Vitamin D. At T1 we assessed Vit. D, albumin, and transferrin. Vitamin D was performed with Electrochemiluminescence through Elecsys 2010 assay. Patients were fed with blended homemade meals. RESULTS: 200 patients (118 males), 22-92 years of age, were studied. There were initial low values for Vit. D (181), albumin (96), transferrin (121), and BMI (124). A correlation was found between Vit. D and serum albumin (r=0.49, p=0.005) but not with transferrin (r=0.26, p=0.195). At T1 the subgroup who had Vit. D levels assessed (n=48) was part of the initial study group maintained low levels of Vitamin D despite nutritional intervention. CONCLUSION: We recommend systematic Vitamin D supplementation of PEG fed patients using homemade meals or at least screening for hypovitaminosis D as a routine part of their care.

Association between change in serum bicarbonate and change in thyroid hormone levels in patients receiving conventional or more frequent maintenance haemodialysis.

AIM: Correction of metabolic acidosis in patients with chronic kidney disease has been associated with improvement in thyroid function. We examined whether changes in bicarbonate were associated with changes in thyroid function in patients with end-stage renal disease receiving conventional or more frequent haemodialysis. METHODS: In the Frequent Hemodialysis Network Trials, the relationship between changes in serum bicarbonate, free triiodothyronine (FT3) and free thyroxine (FT4) was examined among 147 and 48 patients with endogenous thyroid function who received conventional (3×/week) or more frequent (6×/week) haemodialysis (Daily Trial) or who received conventional or more frequent nocturnal haemodialysis (Nocturnal Trial). Equilibrated normalized protein catabolic rate (enPCR) was examined to account for nutritional factors affecting both acid load and thyroid function. RESULTS: Increasing dialysis frequency was associated with increased bicarbonate level. Baseline bicarbonate level was not associated with baseline FT3 and FT4. Change in bicarbonate level was not associated with changes in FT3 and FT4 in the Daily Trial nor for FT4 in the Nocturnal Trial (r ≤ 0.14, P > 0.21). While, a significant correlation between change in serum bicarbonate and change in FT3 (r = 0.44, P = 0.02) was observed in the Nocturnal Trial; findings were no longer significant after adjusting for change in enPCR (r = 0.37, P = 0.08). For participants with baseline bicarbonate <23 mmol/L, no association between change in bicarbonate and change in thyroid indices were seen in the Daily Trial; for the Nocturnal Trial, findings were also not significant for change in FT3 and the association between change in bicarbonate and change in FT4 (r = 0.54, P = 0.03) was no longer significant after adjusting for enPCR (r = 0.45, P = 0.11). CONCLUSION: Changes in bicarbonate were not associated with changes in thyroid hormone levels after adjusting for enPCR, as a marker of nutritional status. Future studies should examine whether improvement in acid base status improves thyroid function in haemodialysis patients with evidence of thyroid hypofunction.

Relationship between protein-energy wasting in adults with chronic hemodialysis and the response to treatment with erythropoietin.

BACKGROUND: It is known that one of the leading causes of morbidity in chronic kidney disease (CKD) is the anemic syndrome. Although the pathogenic mechanisms of anemia are multiple, erythropoietin deficiency appears as the dominant factor. Patients in hemodialysis (HD) have a high prevalence of protein energy wasting (PEW) that may explains the poor response to Erythropoietin (EPO). METHODS: Retrospective cohort study of patients on HD from January to December 2014. The participants were classified according to a diagnostic of PEW using the "Malnutrition Inflammation Score" (MIS) and bioimpedance analysis (BIA) measurement of body composition at the start of erythropoietin therapy and after 3 months of follow up. We performed descriptive statistics and analyzed the differences between groups with and without PEW considering their responsiveness. In addition, we calculated the relative risk of EPO resistance, considering p value < 0.05 as statistically significant. RESULTS: Sixty-one patients ended the follow up. Both groups were similar in basal hemoglobin, hematocrit and other hematopoiesis markers (p = NS). Patients without PEW have a decrease risk for poor response to treatment with EPO (RR = 0.562 [95% CI, 0.329-0.961-]) than those with PEW. Finally, hemoglobin concentrations were evaluated at baseline and every four weeks until week 12, finding a statistically significant improvement only in patients without PEW according MIS (p < 0.05). CONCLUSIONS: PEW is an incremental predictor of poor responsiveness to EPO in HD patients, thus, it is important to consider correcting malnutrition or wasting for a favorable response to treatment with EPO.

Reduced glucose-induced insulin secretion in low-protein-fed rats is associated with altered pancreatic islets redox status.

In the present study, we investigated the relationship between early life protein malnutrition-induced redox imbalance, and reduced glucose-stimulated insulin secretion. After weaning, male Wistar rats were submitted to a normal-protein-diet (17%-protein, NP) or to a low-protein-diet (6%-protein, LP) for 60 days. Pancreatic islets were isolated and hydrogen peroxide (H2 O2 ), oxidized (GSSG) and reduced (GSH) glutathione content, CuZn-superoxide dismutase (SOD1), glutathione peroxidase (GPx1) and catalase (CAT) gene expression, as well as enzymatic antioxidant activities were quantified. Islets that were pre-incubated with H2 O2 and/or N-acetylcysteine, were subsequently incubated with glucose for insulin secretion measurement. Protein malnutrition increased CAT mRNA content by 100%. LP group SOD1 and CAT activities were 50% increased and reduced, respectively. H2 O2 production was more than 50% increased whereas GSH/GSSG ratio was near 60% lower in LP group. Insulin secretion was, in most conditions, approximately 50% lower in LP rat islets. When islets were pre-incubated with H2 O2 (100 µM), and incubated with glucose (33 mM), LP rats showed significant decrease of insulin secretion. This effect was attenuated when LP islets were exposed to N-acetylcysteine.

Leptin and ghrelin in chronic kidney disease: their associations with protein-energy wasting.

BACKGROUND: This study aimed to evaluate plasma concentrations of leptin and total ghrelin in children with chronic kidney disease (CKD) and assess their roles in protein-energy wasting (PEW). METHODS: This study consisted of three different CKD populations [CKD group (20 patients with non-dialysis CKD), dialysis group (39 patients on dialysis), and kidney transplant (KTx) group (35 KTx recipients)] and control group (18 healthy children). Plasma leptin and total ghrelin levels were measured. Multi-frequency bioimpedance analysis was used for the assessment of fat and lean mass. PEW was defined using criteria including body mass, muscle mass, growth, serum albumin level, and protein intake. RESULTS: While plasma leptin levels did not differ among the study groups, total ghrelin levels were significantly higher in the dialysis group (P < 0.001). Seven dialysis patients (18%) and one CKD patient (5%) but none of the KTx recipients met the criteria of PEW. Dialysis patients with PEW had lower plasma leptin levels compared to their counterparts (P = 0.018); however, total ghrelin levels did not differ between the two groups (P = 0.10). Low leptin level in dialysis patients was independently associated with lower fat mass index (P < 0.001) and lower height-specific SD scores of BMI (P = 0.019). CONCLUSIONS: PEW is prevalent in dialysis patients. Low levels of leptin seem to be associated with PEW. Our result suggests that low leptin levels may be a consequence rather than a cause of PEW. Longitudinal studies are required to investigate this complex relationship between leptin and PEW in pediatric dialysis patients.

Prevalence and associated factors of protein- energy wasting among patients with chronic kidney disease at Mulago hospital, Kampala-Uganda: a cross-sectional study.

BACKGROUND: Chronic kidney disease (CKD) is global health concern and priority. It is the 12th leading cause of death worldwide. Protein Energy Wasting occurs in 20-25% of patients with chronic kidney disease and can lead to a high morbidity and mortality rate. We determined the prevalence of protein energy wasting and factors associated among patients with chronic kidney disease at Mulago National Referral Hospital, Kampala, Uganda. METHODS: We conducted a cross-sectional study recruiting 182 (89 non-CKD patients and 93 CKD patients) consecutively from the outpatient clinic and wards on New Mulago Hospital complex. We took anthropometric measurements including heights, weights, Triceps skin fold (TSF), Mid- Upper Arm circumference (MUAC), Body Mass Index (BMI) and Mid-arm muscle circumference (MAMC). Serum albumin levels and lipid profile levels were also obtained. Following consent of study participants, Data was collected using questionnaires and analyzed using STATA 14.1. Percentages, frequencies, means, medians, standard deviation and interquartile range were used to summarise data. Crude and adjusted binary logistic regression was performed to assess unadjusted and adjusted effect measures of protein energy wasting due to several factors. Stratification by CKD status was performed during the analysis to minimize confounding. RESULTS: The median age for CKD patients was 39 years compared to 27 years for non-CKD participants (p < 0.001). The prevalence of protein energy wasting (PEW) was 68.6% in this study with 47.3 and 21.3% among CKD and non-CKD participants respectively. Factors which were associated with PEW included CKD age between 18 and 24, being single, catholic religion, CKD stage 4, Hb < 11.5 g/dl and LDL > 160 mg/dl. CONCLUSION: Protein energy Wasting is prevalent among patients with chronic kidney disease and clinicians should routinely screen for it during patient care.

Hormonal Correlates and Predictors of Nutritional Recovery in Malnourished African Children.

Background: Malnourished children show variable growth responses to nutritional rehabilitation. We aimed to investigate whether these differences could be explained by variations in growth and energy-regulating hormones. Methods: Quasi-experimental study: Children aged 6-24 months in rural Gambia were recruited to controls if weight-for-height z-score (WHZ) > -2 (n = 22), moderate acute malnutrition if WHZ < -2 and > -3 (n = 18) or severe acute malnutrition if WHZ < -3 (n = 20). Plasma hormone and salivary CRP levels were determined by ELISA. Results: In univariable analyses, increases in weight-for-age z-score (WAZ) in malnourished children were positively correlated with insulin (F-ratio 7.8, p = 0.006), C-peptide (F-ratio 12.2, p < 0.001) and cortisol (F-ratio 5.0, p = 0.03). In multivariable analysis, only baseline C-peptide (F-ratio 7.6, p = 0.009) predicted the changes in WAZ over 28 days of interventions. Conclusion: In rural Gambian, malnourished children, although it cannot be used in isolation, baseline C-peptide was a predictor of future response to rehabilitation.

The relationship of serum adipokines with malnutrition inflammation score in haemodialysis.

BACKGROUND: Protein-energy wasting is a prevalent disorder in haemodialysis. Zinc-α2-glycoprotein (ZAG) and adipose triglyceride lipase (ATGL) are novel adipokines with recognized lipolytic effects and proposed role in metabolic homoeostasis. This study was conducted to investigate the association of ZAG and ATGL concentrations with malnutrition-inflammation score (MIS) and metabolic profile of patients with haemodialysis. MATERIALS AND METHODS: Eighty-eight patients under regular haemodialysis were divided based on MIS to normal to mild wasting (NMW; n = 35) or moderate wasting (MW; n = 53) group. Anthropometric measurements along with fasting serum concentrations of ZAG, ATGL, free fatty acids (FFAs), albumin, transferrin, total iron-binding capacity (TIBC), hs-CRP, lipid profile and glucose metabolism were assessed. RESULTS: Adipose triglyceride lipase concentration was significantly higher in MW than NMW group (10·89 ± 5·7 vs. 8·02 ± 3·37 mIU/mL; P = 0·008). The ZAG and FFAs were not significantly different between two groups. ATGL was directly correlated with FFAs in all of the patients (r = 0·284, P = 0·007) and MW (r = 0·32, P = 0·021), and marginally in NMW (r = 0·31, P = 0·057) groups. ATGL and odds of having mild or moderate wasting were significantly correlated (OR = 1·21, P = 0·033). A positive association was observed between ATGL with TG (r = 0·31, P = 0·049) and also with transferrin and TIBC (r = 0·44, P = 0·001) only in MW group. An inverse relationship was observed between ATGL and HDL in all of the participants (r=-0·222, P = 0·04). No significant correlation was observed between ZAG and other parameters. CONCLUSIONS: The serum concentrations of ATGL, but not ZAG, were significantly higher in MW compared to NMW group. Each unit increase in ATGL concentrations was correlated with 21% increase in the odds of wasting severity. ATGL might play a role in wasting pathogenesis and metabolic profile in haemodialysis.

Nutritional assessment of elderly patients on dialysis: pitfalls and potentials for practice.

The chronic kidney disease (CKD) population is aging. Currently a high percentage of patients treated on dialysis are older than 65 years. As patients get older, several conditions contribute to the development of malnutrition, namely protein energy wasting (PEW), which may be compounded by nutritional disturbances associated with CKD and from the dialysis procedure. Therefore, elderly patients on dialysis are vulnerable to the development of PEW and awareness of the identification and subsequent management of nutritional status is of importance. In clinical practice, the nutritional assessment of patients on dialysis usually includes methods to assess PEW, such as the subjective global assessment, the malnutrition inflammation score, and anthropometric and laboratory parameters. Studies investigating measures of nutritional status specifically tailored to the elderly on dialysis are scarce. Therefore, the same methods and cutoffs used for the general adult population on dialysis are applied to the elderly. Considering this scenario, the aim of this review is to discuss specific considerations for nutritional assessment of elderly patients on dialysis addressing specific shortcomings on the interpretation of markers, in addition to providing clinical practice guidance to assess the nutritional status of elderly patients on dialysis.

Irisin and Volume Overload are Associated with Protein Energy Wasting in Peritoneal Dialysis Patients.

BACKGROUND/AIMS: Protein energy wasting (PEW) is a common medical phenomenon that is observed in maintenance dialysis patients. PEW also increases morbidity and mortality of these patients. Its pathogenesis is unclear. We hypothesize that serum irisin levels and volume overload may induce PEW in peritoneal dialysis (PD) patients. The aim of this study is to measure serum irisin levels, evaluate volume status of PD patients, and study their correlations with PEW in PD patients. METHODS: This study is a cross-sectional study with 160 PD patients from the PD center of Peking University Third Hospital and 35 healthy control subjects. PD patients were divided into PEW group and non-PEW group according to PEW diagnosis criteria. Serum irisin concentrations were measured by ELISA. Volume overload status (volume overload is defined as overhydration value ≥2 liters) of PD patients was analyzed by bioelectrical impedance. RESULTS: The serum irisin levels were significantly lower in PD patients compared with those of the controls (113.2±11.8 ng/ml vs. 464.2±37.4 ng/ml, P<0.01). The serum irisin levels were lower in PD patients with PEW than those of the patients without PEW (106.5±15.2 ng/ml vs. 117.4±17.6 ng/ml, P<0.01). PEW is more prevalent in patients with volume overload than patients without volume overload (62.5% vs. 43.1%, x2=5.756, P=0.016); however, no direct relationship was found between irisin levels and volume overload status. The independent influencing factors of PEW were serum irisin, serum albumin, and volume overload. CONCLUSION: Our results are the first to provide clinical evidence of the association between serum irisin, volume overload, and PEW in PD patients. PEW may inhibit the release or synthesis of irisin from skeletal muscles, and volume overload may aggravate PEW in PD patients.

Combination of low body mass index and serum albumin level is associated with chronic kidney disease progression: the chronic kidney disease-research of outcomes in treatment and epidemiology (CKD-ROUTE) study.

BACKGROUND: The relationship between protein-energy wasting and chronic kidney disease (CKD) progression is unknown. In the present prospective cohort study, we evaluated the hypothesis that a combination of low body mass index (BMI) and serum albumin level is associated with rapid CKD progression. METHODS: The study cohort comprised 728 predialysis Japanese patients with CKD (stages 2-5) enrolled from 2010 to 2011. Patients were categorized into four groups according to their serum albumin levels and BMI: group 1, low serum albumin level (<4 g/dL) and low BMI (<23.5 kg/m2); group 2, high serum albumin level (≥4 g/dL) and low BMI; group 3, low serum albumin level and high BMI (≥23.5 kg/m2); and group 4, high serum albumin level and high BMI. The primary outcome was a 30 % decline in estimated glomerular filtration rate (eGFR) or start of dialysis within 2 years. The secondary outcome was an annual GFR decline (mL/min/1.73 m2/year). RESULTS: Logistic regression analysis adjusted for baseline characteristics (reference, group 4) showed that only group 1 was associated with a significant risk of CKD progression, with adjusted odds ratio of 3.51 [95 % confidence interval (CI) (1.63, 7.56)]. A multivariate linear regression analysis adjusted for baseline characteristics showed a significant difference in annual eGFR decline between groups 1 and 4 [coefficients ß (standard error) -2.62 (0.75), p = 0.001]. CONCLUSION: This study suggests that combined effects of low BMI (<23.5 kg/m2) and serum albumin level (<4 g/dL) are associated with CKD progression.

A Practical Standardized Composite Nutrition Score Based on Lean Tissue Index: Application in Nutrition Screening and Prediction of Outcome in Hemodialysis Population.

OBJECTIVE: Rapid screening and monitoring of nutritional status is mandatory in hemodialysis population because of the increasingly encountered nutritional problems. Considering the limitations of previous composite nutrition scores applied in this population, we tried to develop a standardized composite nutrition score (SCNS) using low lean tissue index as a marker of protein wasting to facilitate clinical screening and monitoring and to predict outcome. DESIGN AND METHODS: This retrospective cohort used 2 databases of dialysis populations from Taiwan between 2011 and 2014. First database consisting of data from 629 maintenance hemodialysis patients was used to develop the SCNS and the second database containing data from 297 maintenance hemodialysis patients was used to validate this developed score. RESULTS: SCNS containing albumin, creatinine, potassium, and body mass index was developed from the first database using low lean tissue index as a marker of protein wasting. When applying this score in the original database, significantly higher risk of developing protein wasting was found for patients with lower SCNS (odds ratio 1.38 [middle tertile vs highest tertile, P < .0001] and 2.40 [lowest tertile vs middle tertile, P < .0001]). The risk of death was also shown to be higher for patients with lower SCNS (hazard ratio 4.45 [below median level vs above median level, P < .0001]). These results were validated in the second database. CONCLUSION: We developed an SCNS consisting of 4 easily available biochemical parameters. This kind of scoring system can be easily applied in different dialysis facilities for screening and monitoring of protein wasting. The wide application of body composition monitor in dialysis population will also facilitate the development of specific nutrition scoring model for individual facility.

Association of anemia with functional and nutritional status in the German multicenter study "GeriAnaemie2013".

OBJECTIVES: Anemia and malnutrition are risk factors for frailty in older people but data from multicenter studies among German geriatric inpatients are lacking. This analysis evaluated data from the multicenter study "GerAnaemie2013" commissioned by the German Geriatric Society. PATIENTS AND METHODS: The study involved an analysis of the 579 geriatric inpatients recruited in the context of the German multicenter study "GeriAnaemie2013". Study parameters: Barthel index (BI), handgrip strength, nutritional data (e.g. loss of appetite, loss of weight and decreased food intake). INCLUSION CRITERIA: in-patient age ≥70 years, exclusion criteria: current cancer disease or cancer-associated treatment. Anemia was defined according to the World Health Organization (WHO) criteria. RESULTS: The mean age of patients was 81.9 years, overall prevalence of anemia 55.1 %, mean hemoglobin (Hb) level 11.9 g/dl, average BI 50.8 points and 30.3 % of all patients were at risk of malnutrition. While univariate analysis revealed a significantly lower BI in anemic patients, this association was no longer seen in multivariate analysis. Regression analysis revealed that a drug intake of > 5 drugs/day doubles the chance of suffering from anemia with an adjusted odds ratio (OR) of 2.17 (confidence interval (CI) 1.28-3.68, p = 0.004) as well as a serum albumin level below 3.5 g/dl with an adjusted OR of 2.11 (range 1.40-3.19, p < 0.001). CONCLUSION: Polymedication and low serum albumin were independent risk factors for anemia in geriatric patients, probably reflecting disease severity.

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.

Effect of a mixture of GOS/FOS® on calcium absorption and retention during recovery from protein malnutrition: experimental model in growing rats.

INTRODUCTION: During growth, protein deprivation impairs epiphyseal growth plate (EGP) height, bone volume (BV) and endochondral ossification. During catch-up growth, Ca availability becomes essential to ensure the extra amount needed to achieve optimal peak bone mass and strength. GOS and FOS improve mineral absorption in the colon. PURPOSE: The effect of a mixture of GOS/FOS® 9:1 added to a 0.5 %Ca (NCa) and a 0.3 %Ca (LCa) diets on Ca, P and Mg absorptions and bone mineralization, density and structure using an experimental model of growing rats recovering from early protein malnutrition was investigated. METHODS: To induce protein malnutrition, rats were fed a low protein diet: 4 % (LPD) during 1 week and then were randomly assigned to recovery groups (R) until day 50 (T = 50) as follows: R0.5 %: NCa; RP0.5 %: NCa + 5.3 % GOS/FOS®; R0.3 %: LCa and RP0.3 %: LCa + 5.3 % GOS/FOS®. Control groups received the 0.5 %Ca or 0.3 %Ca diet from weaning until day 40 or 50. RESULTS: Body weight and length increased in C groups throughout the study; both were arrested in all R during LPD consumption and increased immediately after re-feeding. Independently of dietary Ca content, LS counts, ß-glucosidase and Ca, P and Mg absorption increased, whereas cecum pH, ß-glucuronidase, urease and tryptophanase decreased in RP0.5 %: and RP0.3 %: as compared to the other studied groups (p < 0.01). Prebiotic consumption decreased CTX levels and increased femur Ca, Mg and P contents, total skeleton bone mineral content, proximal tibia and spine BMD, BV, EGP height and hypertrophic zone thickness, stiffness and elastic modulus as compared to recovery groups fed the prebiotic-free diets. CONCLUSION: Under the present experimental conditions, GOS/FOS® mixture induced colonic positive effects, which increased Ca, P and Mg absorption. Thus, consuming the prebiotic-containing diet resulted in an extra amount of minerals that improved bone development in growing rats recovering from protein malnutrition.

Irisin is Associated with Urotensin II and Protein Energy Wasting in Hemodialysis Patients.

AIMS/INTRODUCTION: Irisin is a newly identified myokine which can promote energy expenditure. Urotensin II (UII) is identified as the most potent mammalian vasoconstrictor to date. Previous studies showed that UII can aggravate insulin resistance while irisin alleviate insulin resistance. Through this study, it is our aim to elucidate if UII can induce insulin resistance and also have an association with the irisin level in hemodialysis (HD) patients. MATERIALS AND METHODS: One hundred and twenty-eight patients on maintenance hemodialysis treatment and forty healthy subjects were enrolled in this study. Blood irisin concentrations and UII concentrations were measured by ELISA and RIA respectively. The body composition was analyzed by bioelectrical impedance. RESULTS: The serum irisin levels and UII levels were both significantly lower in HD patients in comparison to that of the healthy subjects. The serum irisin levels were lower in HD patients with protein energy wasting than those of the patients without protein energy wasting. The independent determinants of circulating Ln (irisin) (the natural logarithm of irisin) were UII lean body mass and patients with protein energy wasting. CONCLUSIONS: Our results are the first to provide the clinical evidence of the association among irisin, UII, and protein energy wasting. Our results hint that UII and protein energy wasting might inhibit the release or synthesis of irisin from skeletal muscles in HD patients.

Predictors of protein-energy wasting in haemodialysis patients: a cross-sectional study.

BACKGROUND: Protein-energy wasting (PEW) is a highly prevalent condition in haemodialysis patients (HD). The potential usefulness of nutritional-inflammatory markers in the diagnosis of PEW in chronic kidney disease has not been established completely. We hypothesised that a combination of serum albumin, percentage of mid-arm muscle circumference and standard body weight comprises a better discriminator than either single marker of nutritional status in HD patients. METHODS: A cross-sectional study was performed in 80 HD patients. Patients were categorised in two groups: well-nourished and PEW. Logistic regression analysis was applied to corroborate the reliability of the three markers of PEW with all the nutritional-inflammatory markers analysed. RESULTS: PEW was identified in 52.5% of HD patients. Compared with the well-nourished patients, PEW patients had lower body mass index, serum pre-albumin and body cell mass (all P < 0.001) and higher C-reactive protein (s-CRP) (P < 0.01). Logistic regression analyses showed that the combination of the three criteria were significantly related with s-CRP >1 mg dL(-1) , phase angle <4°, and serum pre-albumin <30 mg dL(-1) (all P < 0.05). Other indicators, such as lymphocytes <20% and Charlson comorbidity index, were significantly involved (both P < 0.01). A receiver operating characteristic curve (area under the curve) of 0.86 (P < 0.001) was found. CONCLUSIONS: The combined utilisation of serum albumin, percentage of mid-arm muscle circumference and standard body weight as PEW markers appears to be useful for nutritional-inflammatory status assessment and adds predictive value to the traditional indicators. Larger studies are needed to achieve the reliability of these predictor combinations and their cut-off values in HD patients and other populations.

Comparing Tests Assessing Protein-Energy Wasting: Relation With Quality of Life.

OBJECTIVE: Protein-energy wasting (PEW), a state of decreased bodily protein and energy fuels, is highly prevalent among hemodialysis patients. The best method to determine PEW, however, remains debated. As an independent, negative association between PEW and quality of life (QOL) has been demonstrated, establishing which nutrition-related test correlates best with QOL may help to identify how PEW should preferably be assessed. DESIGN AND METHODS: Data were used from CONTRAST, a cohort of end-stage kidney disease patients. At baseline, Subjective Global Assessment (SGA), Malnutrition Inflammation Score (MIS), Geriatric Nutritional Risk Index, composite score on protein-energy nutritional status, normalized protein nitrogen appearance, body mass index, serum albumin, and serum creatinine were determined. QOL was assessed by the Kidney Disease Quality of Life Short Form 1.3. The present study reports on 2 general and 11 kidney disease-specific QOL scores. Spearman's rho (ρ) was calculated to determine correlations between nutrition-related tests and QOL domains. Twelve months after randomization, a sensitivity analysis was performed to test the robustness of the results. RESULTS: Of 714 patients, 489 representative subjects were available for analysis. All tests correlated with the Physical Component Score, except body mass index. Only SGA and MIS correlated significantly with the Mental Component Score. SGA correlated significantly with 10 of 11 kidney disease-specific QOL domains. The MIS not only correlated significantly with all (11) kidney disease-specific QOL domains but also with higher correlation coefficients. CONCLUSION: Of the 8 investigated nutrition-related tests, only MIS correlates with all QOL domains (13 of 13) with the strongest associations.

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.

Baseline higher peritoneal transport had been associated with worse nutritional status of incident continuous ambulatory peritoneal dialysis patients in Southern China: a 1-year prospective study.

The aim of the present study was to investigate the relationship between baseline peritoneal transport types and nutritional status in Chinese continuous ambulatory peritoneal dialysis (CAPD) patients. In the present single-centre, prospective study, incident CAPD patients were included from 15 April 2010 to 31 December 2011 and were followed up for 12 months. According to the results of baseline peritoneal equilibration test, patients were divided into lower peritoneal transport group (lower transporters) and higher peritoneal transport group (higher transporters). Nutritional status was evaluated by both subjective global assessment (SGA) and protein-energy wasting (PEW) score. The body composition parameters were assessed by body impedance analysis. A total of 283 CAPD patients were included in the study, of which 171 (60.4 %) were males with a mean age of 47.0 (sd 14.9) years. Compared with lower transporters (n 92), higher transporters (n 181) had lower levels of serum albumin (37.1 (sd 4.3) v. 39.6 (sd 4.3) g/l, P< 0.001), serum pre-albumin (356 (sd 99) v. 384 (sd 90) mg/l, P= 0.035), phase angle (6.15 (sd 0.39) v. 6.27 (sd 0.47)°, P< 0.05) and higher rate of malnutrition defined by SGA (52.5 v. 25.0%, P< 0.001) and PEW score (37.0 v. 14.1 %, P< 0.001) at 1-year of follow-up. Baseline higher peritoneal transport, analysed by multivariate binary logistic regressions, was independently associated with malnutrition (SGA mild to moderate and severe malnutrition: OR 3.43, 95% CI 1.69, 6.96, P< 0.01; PEW: OR 2.40, 95% CI 1.08, 5.31, P= 0.03). It was concluded that baseline higher peritoneal transport was independently associated with worse nutritional status of CAPD patients in Southern China.