A Comparative Analysis of Nutritional Assessment Using Global Leadership Initiative on Malnutrition Versus Subjective Global Assessment and Malnutrition Inflammation Score in Maintenance Hemodialysis Patients.

OBJECTIVE: Malnutrition is a prevalent condition in maintenance hemodialysis (MHD) patients. This study aimed to evaluate the performance of the recently developed GLIM (Global Leadership Initiative on Malnutrition) in MHD by assessing the agreement, accuracy, sensitivity, specificity, and survival prediction of GLIM when compared to 7-point subjective global assessment (7p-SGA) and malnutrition inflammation score (MIS). DESIGN AND METHODS: We investigated 2 cohorts: MHDltaly (121 adults from Italy; 67 ± 16 years, 65% men, body mass index 25 ± 5 kg/m2) and MHDBrazil (169 elderly [age > 60 years] from Brazil; 71 ± 7 years, 66% men, body mass index 25 ± 4 kg/m2), followed for all-cause mortality for median 40 and 17 months, respectively. We applied the 2-step approach from GLIM: (1) screening and (2) confirming malnutrition by phenotypic and etiologic criteria. For 7p-SGA and MIS, a score ≤5 and ≥8, respectively, defined malnutrition. RESULTS: Malnutrition was present in 38.8% by GLIM, 25.6% by 7p-SGA, and 29.7% by MIS in the MHDItaly cohort, and in 47.9% by GLIM, 59.8% by 7p-SGA, and 49.7% by MIS in the MHDBrazil cohort. Cohen's kappa coefficient (κ) showed only "fair" agreement between GLIM and SGA (MHDItaly: κ = 0.26, P = .003; MHDBrazil: κ = 0.22, P = .003) and between GLIM and MIS (MHDItaly: κ = 0.33, P < .001; MHDBrazil: κ = 0.25, P = .001). Cox regression analysis showed that all 3 methods were able to predict mortality in crude analysis; however in the adjusted model, the association seemed more consistent and stronger in magnitude for 7p-SGA and MIS. CONCLUSION: In MHD patients, GLIM showed low agreement, sensitivity, and accuracy in identifying malnourished subjects by either 7p-SGA or MIS. Considering the specific wasting characteristics that predominate in MHD, the well-established 7p-SGA and MIS methods may be more useful in this clinical setting.

Socioeconomic position links circulatory microbiota differences with biological age.

Imbalanced nutrition is associated with accelerated ageing, possibly mediated by microbiota. An analysis of the circulatory microbiota obtained from the leukocytes of participants in the MRC Twenty-07 general population cohort was performed. We now report that in this cohort, the most biologically aged exhibit a significantly higher abundance of circulatory pathogenic bacteria, including Neisseria, Rothia and Porphyromonas, while those less biologically aged possess more circulatory salutogenic (defined as being supportive of human health and wellbeing) bacteria, including Lactobacillus, Lachnospiraceae UCG-004 and Kocuria. The presence of these salutogenic bactreria is consistent with a capacity to metabolise and produce Nrf2 agonists. We also demonstrate that associated one carbon metabolism, notably betaine levels, did not vary with chronological age, but displayed a difference with socioeconomic position (SEP). Those at lower SEP possessed significantly lower betaine levels indicative of a poorer diet and poorer health span and consistent with reduced global DNA methylation levels in this group. Our data suggest a clear route to improving age related health and resilience based on dietary modulation of the microbiota.

Hypoalbuminemia: a price worth paying for improved dialytic removal of middle-molecular-weight uremic toxins?

Hemodiafiltration (HDF) increases the removal of middle-molecular-weight uremic toxins and may improve outcomes in patients with end-stage kidney disease (ESKD), but it requires complex equipment and comes with risks associated with infusion of large volumes of substitution solution. New high-flux hemodialysis membranes with improved diffusive permeability profiles do not have these limitations and offer an attractive alternative to HDF. However, both strategies are associated with increased albumin loss into the dialysate, raising concerns about the potential for decreased serum albumin concentrations that have been associated with poor outcomes in ESKD. Many factors can contribute to hypoalbuminemia in ESKD, including protein energy wasting, inflammation, volume expansion, renal loss and loss into the dialysate; of these factors, loss into the dialysate is not necessarily the most important. Furthermore, recent studies suggest that mild hypoalbuminemia per se is not an independent predictor of increased mortality in dialysis patients, but in combination with inflammation it is a poor prognostic sign. Thus, whether hypoalbuminemia predisposes to increased morbidity and mortality may depend on the presence or absence of inflammation. In this review we summarize recent findings on the role of dialysate losses in hypoalbuminemia and the importance of concomitant inflammation on outcomes in patients with ESKD. Based on these findings, we discuss whether hypoalbuminemia may be a price worth paying for increased dialytic removal of middle-molecular-weight uremic toxins.

Serum albumin, inflammation, and nutrition in end-stage renal disease: C-reactive protein is needed for optimal assessment.

Low serum albumin (S-Alb) is a frequent feature of end-stage renal disease (ESRD) that independently predicts mortality. Serum albumin has mainly been considered a biomarker of visceral protein and immunocompetence status, fundamental to nutritional assessment. However, low S-albumin level is associated with persistent systemic inflammation and many bodies of evidence show that S-Alb has a limited role as a marker of nutritional status. We reported that a low S-Alb concentration was an independent risk factor for poor outcome in ESRD only in the presence of systemic inflammation. Moreover, the relationships between inflammatory biomarkers and outcome are confounded also by alterations in body composition (such as obese sarcopenia) and oxidative stress. Taken together, S-Alb alone should not be used as a proxy of the nutritional status in a dialysis patient. Its association with dietary intake is poor and low S-Alb values are most often non-nutritional in origin. When analyzing S-Alb to predict mortality risk in ESRD, it should always be combined with measurement of hsCRP.

Prevalence and Risk of Protein-Energy Wasting Assessed by Subjective Global Assessment in Older Adults With Advanced Chronic Kidney Disease: Results From the EQUAL Study.

OBJECTIVES: Prevalence and risk factors for protein-energy wasting (PEW) are poorly studied in the nondialysis, older population with advanced chronic kidney disease (CKD). Our aim was to evaluate the prevalence of PEW in advanced stage CKD patients aged greater than 65 years. Furthermore, we aimed to describe risk factors for PEW in the overall study population and among obese individuals. DESIGN: Prospective observational cohort study. METHODS: The EQUAL study, a European Quality Study on treatment in advanced chronic kidney disease, is a multicenter prospective observational cohort study in six European countries. We included patients aged ≥65 years with incident glomerular filtration rate <20mL/min/1.73m2 not on dialysis attending nephrology care. PEW was assessed by 7-point Subjective Global Assessment (7-p SGA). RESULTS: In general, the study cohort (n = 1,334) was overweight (mean body mass index [BMI] 28.4 kg/m2). The majority of the patients had a normal nutritional status (SGA 6-7), 26% had moderate PEW (SGA 3-5), and less than 1% had severe PEW (SGA 1-2). Muscle wasting and loss of fat tissue were the most frequent alterations according to the SGA subscales, especially in those aged >80 years. The prevalence of PEW was higher among women, increased with age, and was higher in those with depression/dementia. PEW was the most common in those with underweight (BMI <22 kg/m2), 55% or normal weight (BMI 22-25 kg/m2), 40%. In obese individuals (BMI >30 kg/m2), 25% were diagnosed with protein wasting. Risk factors for SGA ≤5 in obese people were similar to those for the overall study population. CONCLUSION: This European multicenter study shows that the prevalence of PEW is high in patients with advanced CKD aged >65 years. The risk of PEW increases substantially with age and is commonly characterized by muscle wasting. Our study suggests that focus on nutrition should start early in the follow-up of older adults with CKD.

Clinical global assessment of nutritional status as predictor of mortality in chronic kidney disease patients.

BACKGROUND: The value of subjective global assessment (SGA) as nutritional assessor of protein-energy wasting (PEWSGA) in chronic kidney disease (CKD) patients depends on its mortality predictive capacity. We investigated associations of PEWSGA with markers of nutritional status and all-cause mortality in CKD patients. METHODS: In 1031 (732 CKD1-5 non-dialysis and 299 dialysis) patients, SGA and body (BMI), lean (LBMI) and fat (FBMI) body mass indices, % handgrip strength (% HGS), serum albumin, and high sensitivity C-reactive protein (hsCRP) were examined at baseline. The five-year all-cause mortality predictive strength of baseline PEWSGA and during follow-up were investigated. RESULTS: PEWSGA was present in 2% of CKD1-2, 16% of CKD3-4, 31% of CKD5 non-dialysis and 44% of dialysis patients. Patients with PEWSGA (n = 320; 31%) had higher hsCRP and lower BMI, LBMI, FBMI, %HGS and serum albumin. But, using receiver operating characteristics-derived cutoffs, these markers could not classify (by kappa statistic) or explain variations of (by multinomial logistic regression analysis) presence of PEWSGA. In generalized linear models, SGA independently predicted mortality after adjustments of multiple confounders (RR: 1.17; 95% CI: 1.11-1.23). Among 323 CKD5 patients who were re-assessed after median 12.6 months, 222 (69%) remained well-nourished, 37 (11%) developed PEWSGA de novo, 40 (12%) improved while 24 (8%) remained with PEWSGA. The latter independently predicted mortality (RR: 1.29; 95% CI: 1.13-1.46). CONCLUSIONS: SGA, a valid assessor of nutritional status, is an independent predictor of all-cause mortality both in CKD non-dialysis and dialysis patients that outperforms non-composite nutritional markers as prognosticator.

Accelerated ageing and renal dysfunction links lower socioeconomic status and dietary phosphate intake.

BACKGROUND: We have sought to explore the impact of dietary Pi intake on human age related health in the pSoBid cohort (n=666) to explain the disparity between health and deprivation status in this cohort. As hyperphosphataemia is a driver of accelerated ageing in rodent models of progeria we tested whether variation in Pi levels in man associate with measures of biological ageing and health. RESULTS: We observed significant relationships between serum Pi levels and markers of biological age (telomere length (p=0.040) and DNA methylation content (p=0.028), gender and chronological age (p=0.032). When analyses were adjusted for socio-economic status and nutritional factors, associations were observed between accelerated biological ageing (telomere length, genomic methylation content) and dietary derived Pi levels among the most deprived males, directly related to the frequency of red meat consumption. CONCLUSIONS: Accelerated ageing is associated with high serum Pi levels and frequency of red meat consumption. Our data provide evidence for a mechanistic link between high intake of Pi and age-related morbidities tied to socio-economic status.

Activity-related energy expenditure of patients undergoing hemodialysis.

OBJECTIVES: The aim of this study was to evaluate the activity-related energy expenditure (AEE) of patients undergoing hemodialysis (HD) and to compare it with that of healthy controls. DESIGN: This was a cross-sectional study. SETTING: This was an in-center study conducted at the Dialysis Unit, Nephrology Division, Federal University of São Paulo-Oswaldo Ramos Foundation, Brazil. PATIENTS AND METHODS: AEE was evaluated in 32 patients undergoing HD (20 men, aged: 46.3 ± 12.2 years). A subgroup consisting of 22 patients was pair-matched by gender and age with 22 sedentary, healthy individuals. AEE was measured over a period of 5 days using a portable physical activity monitor. Body fat and lean body mass were assessed by dual energy X-ray absorptiometry and body cell mass by bioelectrical impedance analysis. RESULTS: AEE correlated positively with lean body mass and body cell mass, and negatively with age, body fat, and body mass index. From the multiple regression analysis, it was found that age and lean body mass (r(2) = 0.32) or body cell mass (r(2) = 0.30) were the best among the variables that explained variations in AEE. AEE of HD patients in comparison with healthy controls was found to be lower on dialysis days (234 [9.5 to 1,145] kcal/day vs. 565 [214 to 1,319] kcal/day, median [range]; P < .01) as well as on nondialysis days (369 [89.5 to 1,242] kcal/day vs. 565 [214 to 1,319] kcal/day; P = .02). Total energy expenditure of the HD patients on dialysis days (2,051 ± 289 kcal/day) as well as nondialysis days (2,202 ± 283 kcal/day) was also found to be lower in comparison with controls (2,514 ± 307 kcal/day; P < .01). The average contribution of the AEE toward total energy expenditure in HD patients was 15%, whereas in controls it was 24% (P = .03). CONCLUSION: As compared with sedentary, healthy individuals, AEE was reported to be considerably lower in HD patients.

Systemic and local inflammation in peritoneal dialysis: mechanisms, biomarkers and effects on outcome.

Thanks to the technological development in peritoneal dialysis (PD) during the last three decades, the most important problem nowadays for the nephrologists is the maintenance of the long-term function of the peritoneal membrane. Although PD may exert an early survival benefit as compared with hemodialysis (HD), long-term PD is often associated with histopathological alterations in the peritoneal membrane that are linked to peritoneal ultrafiltration deficit and increased mortality risk. These alterations are closely related to the presence of a chronic activated (local and systemic) inflammatory response. PD itself may have other factors associated that could further modulate the inflammatory response, such as the bioincompatibility of dialysis solutions, fluid overload and changes in the body composition. Understanding the pathophysiology of inflammation in PD is essential for the adoption of adequate strategies to improve both membrane and patient survival.

Is UCP2 gene polymorphism associated with decreased resting energy expenditure in nondialyzed chronic kidney disease patients?

OBJECTIVE: The deletion/deletion (del/del) polymorphism of uncoupling protein 2 (UCP2) was associated with decreased energy expenditure in diabetic and obese patients. There is evidence of decreased resting energy expenditure (REE) in chronic kidney disease (CKD) patients not yet on dialysis. However, whether REE is associated with the UCP2 polymorphism was not previously investigated in this population. This study evaluated whether the del/del polymorphism of the UCP2 gene is associated with lower REE in nondialyzed CKD patients. DESIGN: This was a cross-sectional study. PATIENTS AND METHODS: Forty-four nondialyzed CKD patients (29 male; aged 52 +/- 12 years; creatinine clearance, 37 +/- 13 mL/min/1.73 m(2) [values are mean +/- SD unless otherwise noted]) were included. Their REE was assessed by indirect calorimetry, and body composition by bioelectrical impedance. High-sensitivity C-reactive protein (hs-CRP) was also evaluated. The insertion/deletion (ins/del) polymorphism of the UCP2 gene was determined in all participants. To test whether the deletion/deletion (del/del) polymorphism of the UCP2 gene was associated with lower REE, the REE of carriers of the del/del genotype (n = 24; group Del) was compared with that of carriers of the insertion and ins/del genotype (n = 20; group Ins). MAIN OUTCOME MEASURE: The main outcome measure was REE. RESULTS: The REE of group Del was similar to that of the group Ins (1379 +/- 239 kcal/day vs. 1360 +/- 289 kcal/day, respectively, P = NS). This result was maintained even after the REE was adjusted for lean body mass by analysis of covariance. In addition, in a multiple-regression analysis using REE as the dependent variable, only lean body mass and hs-CRP were significant predictors of REE. CONCLUSION: The results suggest that the del/del polymorphism of the UCP2 gene is not associated with lower REE in nondialyzed CKD patients.