Malnutrition according to GLIM criteria in stable renal transplant recipients:Reduced muscle mass as predominant phenotypic criterion

Background & aims: Malnutrition has a negative impact on quality of life and survival in renal transplant recipients (RTR). Therefore, malnutrition detection is important in RTR, but this may be hampered by concomitant presence of weight gain and overweight. Recently, the Global Leadership Initiative on Malnutrition (GLIM) developed a set of diagnostic criteria for malnutrition. We aimed to assess the prevalence of malnutrition according to the GLIM criteria and the distribution of phenotypic criteria in RTR. Additionally, we examined the potential value of 24-h urinary creatinine excretion rate (CER) as alternative measure for the criterion reduced muscle mass. Methods: We used data from stable outpatient RTR included in the TransplantLines Cohort and Biobank Study (NCT02811835). Presence of weight loss and reduced intake or assimilation were derived from Patient-Generated Subjective Global Assessment (PG-SGA) item scores. Reduced muscle mass was assessed by multi-frequency bio-electrical impedance analysis (MF-BIA) and defined as an appendicular skeletal muscle mass index (ASMI) < 7 kg/m(2) for men and 5 mg/L. Malnutrition was defined as presence of at least one phenotypic (weight loss and/or low BMI and/or reduced muscle mass) and one etiologic criterion (reduced intake/assimilation and/or disease burden/inflammation). Results: We included 599 RTR (55 +/- 13 years old, 62% male, BMI 27.2 +/- 4.7 kg/m(2)) at a median of 3.1 years after transplantation. According to GLIM criteria, 14% was malnourished, of which 91% met the phenotypic criterion for reduced muscle mass. Similar results were found by using CHI as measure for muscle mass (13% malnutrition of which 79% with reduced muscle mass). Conclusions: Malnutrition is present in one in 7 stable RTR, with reduced muscle mass as the predominant phenotypic criterion. Assessment of nutritional status, most importantly muscle status, is warranted in routine care, to prevent malnutrition in RTR from remaining undetected and untreated. The diagnostic value of 24-h urinary CER in this regard requires further investigation. (C) 2020 The Author(s). Published by Elsevier Ltd

Protein Intake, Fatigue and Quality of Life in Stable Outpatient Kidney Transplant Recipients

Fatigue is a frequent complaint in kidney transplant recipients (KTR), often accompanied by poor quality of life (QoL). The role of nutrition as determinant of fatigue in KTR is largely unexplored. The aims of this study are to examine the association of protein intake with fatigue and QoL in KTR and to identify other determinants of fatigue. This cross-sectional study is part of the TransplantLines Cohort and Biobank Study (NCT03272841). Protein intake was calculated from urinary urea nitrogen (UUN) in 24-h urine samples. Fatigue was assessed by the Checklist Individual Strength (CIS) questionnaire; moderate and severe fatigue were defined as a CIS score of 20–34 and ≥ 35, respectively. QoL was assessed with the RAND-36-Item Health Survey (RAND-36). Associations of protein intake with fatigue and QoL were analyzed using multinomial logistic and linear regression analyses. We included 730 stable outpatient KTR (median age 58 year [IQR 48–65], 57% male) with a mean protein intake of 82.2 ± 21.3 g/d. Moderate and severe fatigue were present in 254 (35%) and 245 (34%) of KTR. Higher protein intake was significantly associated with lower risk of moderate fatigue (OR 0.89 per 10 g/d; 95%CI 0.83–0.98, p = 0.01), severe fatigue (OR 0.85; 95%CI 0.78–0.92, p < 0.001) and was associated with higher physical component summary score of QoL (β 0.74 per 10 g/d; 95%CI 0.39–1.09, p < 0.001). Higher BMI, a history of dialysis, glomerulonephritis as primary kidney disease and a history of combined organ transplantation were also associated with severe fatigue. In conclusion, amongst the potential modifiable factors of fatigue, higher protein intake is independently associated with lower risk of moderate and severe fatigue and with better QoL in KTR. These findings underline the need to incorporate nutritional assessment in the diagnostic work-up of fatigue. Intervention studies are needed to assess the benefits and safety of higher protein intake in KTR

A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways

Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.Peer reviewe

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.Peer reviewe

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries