Phase angle and donor type are determinants of coronary artery calcification in stable kidney transplant recipients at twelve months after transplantation.

BACKGROUND AND AIM: Coronary artery calcification (CAC) partially explains the excess cardiovascular morbidity and mortality after kidney transplantation. This study aimed to investigate determinants of CAC in stable kidney transplant recipients at 12 months post-transplantation. METHODS AND RESULTS: CAC-score was quantified by the Agatston method using non-contrast enhanced computed tomography, and age- and sex-standardized CAC-percentiles were calculated. Univariable and multivariable multinomial logistic regression was performed to study potential determinants of CAC. The independent determinants were included in multivariable multinomial logistic regression adjusting for potential confounders. 203 KTRs (age 54.0 ± 14.7 years, 61.1% male) were included. Participants were categorized into four groups according to CAC percentiles (p = 0 [CAC-score = 0], n = 68; p ≥ 1%-p ≤ 50% [CAC score = 29.0 (4.0-166.0)], n = 31; p > 50 ≤ 75% [CAC score = 101.0 (23.8-348.3)], n = 26; and p>75% [CAC score = 581.0 (148.0-1652)], n = 83). Upon multivariable multinomial logistic regression, patients with a narrower phase angle and patients who had received a graft from a deceased donor had a higher risk of being in the >75th CAC-percentile. CONCLUSIONS: This study identifies not only metabolic and transplant-related factors, but also phase angle, a composite marker of cell integrity, as an independent determinant of CAC at 12 months after kidney transplantation. This study offers new perspectives for future research into the value of bioelectrical impedance analysis in relation to vascular calcification in kidney transplant recipients.

Sarcopenia augments the risk of excess weight on COVID-19 hospitalization: A prospective study using the Lifelines COVID-19 cohort.

OBJECTIVE: We investigated the associations of sarcopenia alone, overweight or obesity, and sarcopenic overweight or obesity with COVID-19 hospitalization. METHODS: Participants from the Lifelines COVID-19 cohort who were infected with COVID-19 were included in this study. Sarcopenia was defined as a relative deviation of muscle mass of ≤ -1.0 SD from the sex-specific mean 24-h urinary creatinine excretion. Overweight or obesity was defined as a body mass index ≥ 25 kg/m2. Sarcopenic overweight or obesity was defined as the presence of overweight or obesity and low muscle mass. COVID-19 hospitalization was self-reported. Logistic regression models were used to analyze the associations of sarcopenia alone, overweight or obesity, and sarcopenic overweight or obesity with COVID-19 hospitalization. RESULTS: Of the 3594 participants infected with COVID-19 and recruited in this study, 173 had been admitted to the hospital. Compared with the reference group, individuals with overweight or obesity and sarcopenic overweight or obesity were 1.78-times and 2.09-times more likely to have been hospitalized for COVID-19, respectively, whereas sarcopenia alone did not increase the risk of COVID-19 hospitalization. CONCLUSIONS: In this middle-aged population, sarcopenic overweight or obesity elevated the risk of hospitalization for COVID-19 in those infected with COVID-19 more than overweight or obesity alone. These data support the relevance of sarcopenic overweight or obesity as a risk factor beyond the geriatric setting and should be considered in risk stratification in future public health and vaccination campaigns.

Protein and energy intake in intensive care unit survivors during the first year of recovery: A descriptive cohort study.

BACKGROUND: Many intensive care unit (ICU) survivors suffer long-term health issues that affect their quality of life. Nutrition inadequacy can limit their rehabilitation potential. This study investigates nutrition intake and support during ICU admission and recovery. METHODS: In this prospective cohort study, 81 adult ICU patients with stays ≥48 h were included. Data on dietary intake, feeding strategies, baseline and ICU characteristics, and 1-year outcomes (physical health and readmission rates) were collected. The number of patients achieving 1.2 gram per kilogram per day of protein and 25 kilocalories per kilogram per day at 3 months, 6 months, and 12 months after ICU admission was recorded. The impact of dietary supplementation during the year was assessed. Baseline characteristics, intake barriers, and rehabilitation's influence on nutrition intake at 12 months were evaluated, along with the effect of inadequate intake on outcomes. RESULTS: After 12 months, only 10% of 60 patients achieved 1.2 g/kg/day protein intake, whereas 28% reached the advised 25 kcal/kg/day energy target. Supplementary feeding significantly increased protein intake at 3, 6, and 12 months (P = 0.003, P = 0.012, and P = 0.033, respectively) and energy intake at 3 months (P = 0.003). A positive relation was found between female sex and energy intake at 12 months after ICU admission (ß = 4.145; P = 0.043) and taste issues were independently associated with higher protein intake (ß = 0.363; P = 0.036). However, achieving upper-quartile protein or energy intake did not translate into improved physical health outcomes. CONCLUSION: Continuous and improved nutrition care is urgently needed to support patients in reaching nutrition adequacy.

Types of fish consumption differ across socioeconomic strata and impact differently on plasma fish-based omega-3 fatty acids: a cross-sectional study.

PURPOSE: We investigated the associations of socioeconomic position (SEP) with total and type of fish intake in a large general population and validated whether types of fish intake were differently associated with plasma EPA and DHA in a subset of the population. METHODS: From the Lifelines Cohort Study, 94,246 participants aged 44 ± 13 years old were included to test the association of two SEP indicators, i.e., education level and household income level, with dietary intakes of total, oily, lean, fried, and other types of fish. In a subset of 575 participants (mean age: 50 ± 13 years), EPA and DHA levels were measured in plasma phospholipids and triglycerides. Dietary fish intake was assessed using Food Frequency Questionnaire. Linear regressions were applied and adjusted for relevant covariates. RESULTS: Compared to the high education level, lower education levels were negatively associated with total, oily, lean, and other fish intake (p < 0.001 for all), and positively associated with fried fish intake (ß (SE): 0.04 (0.04), p < 0.001 for middle education; 0.07 (0.04), p < 0.001 for low education), independently of relevant covariates. Similar results were observed for income levels. In the subset population, total and oily fish intakes were positively associated with plasma EPA and DHA (p < 0.02 for all). Lean and other fish intakes were positively associated with only DHA (p < 0.008 for all), but not EPA, while fried fish was not associated with either EPA or DHA in plasma (p > 0.1 for all). CONCLUSION: Lower SEP was associated with a lower total intake of fish, and of oily and lean fish, but with higher intake of fried fish. Fried fish was not associated with the fish-based EPA and DHA in plasma. Hence, SEP-related differences in fish consumption are both quantitative and qualitative.

Coffee consumption and risk of kidney function decline in a Dutch population-based cohort.

BACKGROUND AND AIMS: Whether coffee consumption is associated with changes in estimated glomerular filtration rate (eGFR) is unknown. We investigated the relationship between coffee consumption and annual eGFR change in a large Dutch population-based study. METHODS AND RESULTS: This study was performed in 78,346 participants without chronic kidney disease (CKD) in the population-based Lifelines Cohort Study. Coffee consumption was assessed at baseline using food frequency questionnaires. Outcomes were annual eGFR change and a composite kidney outcome (defined as eGFR <60 mL/min per 1.73 m2 or >20 % eGFR decline). Multivariable linear and logistic regression analyses were used to evaluate the associations of coffee consumption (categories and cups/day) with kidney outcomes. Overall, 90 % of the participants drank coffee daily and 36 % drank >2-4 cups/day. Unadjusted mean ± SD annual eGFR change ranged from -2.86 ± 2.96 (for non-coffee drinkers) to -2.35 ± 2.62 (for participants consuming >6 cups/day) mL/min per 1.73 m2. During 3.6 ± 0.9 years follow-up, 11.1 % of participants reached the composite kidney outcome. As compared to non-coffee drinkers, higher coffee consumption was associated with less annual eGFR decline in multivariable models (ß [95 % CIs] ranged from 0.15 [0.07, 0.22] for >0-2 cups/day to 0.29 [0.20, 0.38] for >6 cups/day, P-trend <0.001). Consumption of one more cup of coffee per day was associated with a 3 % lower risk of the composite kidney outcome (OR [95%CI], 0.97 [0.96, 0.99]). The inverse association was more pronounced in a subgroup of individuals with diabetes. CONCLUSION: Coffee consumption was inversely associated with annual eGFR change and CKD risk in a large Dutch population-based cohort.

The prevalence of mental frailty in ICU survivors and informal caregiver strain: A 1-year retrospective study of the Frisian aftercare cohort.

Background: Intensive care unit (ICU) survivors often suffer from long-term mental problems and a reduced health-related quality of life (HRQoL). Symptoms of depression, anxiety, and post-traumatic stress disorder may render patients mentally frail post-ICU, resulting in impaired recovery and an increased informal caregiver burden. The aim of this study was to investigate the prevalence of mental frailty up to 12 months after ICU admission and pinpoint markers for early risk-assessment in clinical practice. Methods: A retrospective cohort study (2012-2018) in which clinical and post-ICU data of long-stay (⩾48 h) ICU-patients was used. Mental frailty was identified as clinically relevant symptoms of depression, anxiety, or post-traumatic distress disorder at 12 months after discharge. Results: The prevalence of mental frailty at 12 months post-ICU among the total group of 239 patients was 38%. Mental frailty was defined as clinically relevant symptoms of depression, anxiety, and/or trauma. To achieve this, previously validated cut off values were used for the HADS (HADS-Anxiety ⩾ 8; HADS-Depression ⩾ 8) and TSQ (⩾6), and CSI (⩾7). Conclusion: A significant proportion of ICU-survivors can be identified as mentally frail, which is associated with impaired HRQoL at baseline and post-ICU, and high caregiver strain. These findings emphasize the need for integrative aftercare programs for both the patient and their informal caregivers.

Sleep quality, fatigue, societal participation and health-related quality of life in kidney transplant recipients: a cross-sectional and longitudinal cohort study.

BACKGROUND: Fatigue and impaired health-related quality of life (HRQoL) are common among kidney transplant recipients (KTR). We hypothesized that both may partially be attributable to poor sleep. METHODS: Cross-sectional and longitudinal data of KTR enrolled in the TransplantLines Biobank and Cohort Study were used. Sleep quality was assessed using the Pittsburgh Sleep Quality Index questionnaire. Individual strength (i.e. a composite of fatigue, concentration, motivation and physical activity), societal participation and HRQoL were assessed using validated questionnaires. RESULTS: We included 872 KTR (39% female, age 56 ± 13 years) and 335 healthy controls. In total, 33% of male KTR and 49% of female KTR reported poor sleep quality, which was higher compared with male and female healthy controls (19% and 28%, respectively, P < .001 for both). In logistic regression analyses, female sex, anxiety, active smoking, low protein intake, physically inactive lifestyle, low plasma magnesium concentration, using calcineurin inhibitors, not using mTOR inhibitors and using benzodiazepine agonists were associated with poor sleep quality. In adjusted linear regression analyses, poor sleep was strongly and independently associated with lower individual strength [standardized ß (st.ß) = 0.59, 95% confidence interval (CI) 0.45 to 0.74, P < .001], poorer societal participation (frequency: st.ß = -0.17, 95% CI -0.32 to -0.01, P = .04; restrictions: st.ß = -0.36, 95% CI -0.51 to -0.21, P < .001; satisfaction: st.ß = -0.44, 95% CI -0.59 to -0.28, P < .001) and lower HRQoL (physical: st.ß = -0.53, 95% CI -0.68 to -0.38, P < .001; mental: st.ß = -0.64, 95% CI -0.78 to -0.50, P < .001). The associations with poorer societal participation and lower HRQoL were strongly mediated by individual strength (P < .001 for all), yet the suggested direct effects of poor sleep quality on HRQoL remained significant (Pphysical = .03, Pmental = .002). Longitudinal data of 292 KTR showed that sleep quality improves after kidney transplantation in males (P < .001), but not in females (P = .9). CONCLUSIONS: Poor sleep quality is common among KTR, and may be a potential target to improve fatigue, societal participation and HRQoL among KTR.

Urinary Copper Excretion Is Associated with Long-Term Graft Failure in Kidney Transplant Recipients.

INTRODUCTION: In chronic kidney disease, proteinuria increases urinary copper excretion, inducing oxidative tubular damage and worsening kidney function. We investigated whether this phenomenon occurred in kidney transplant recipients (KTRs). In addition, we studied the associations of urinary copper excretion with the biomarker of oxidative tubular damage urinary liver-type fatty-acid binding protein (u-LFABP) and death-censored graft failure. METHODS: This prospective cohort study was performed in the Netherlands between 2008 and 2017, including outpatient KTR with a functioning graft for longer than 1 year, who were extensively phenotyped at baseline. Twenty-four-hour urinary copper excretion was measured by inductively coupled plasma mass spectrometry. Multivariable linear and Cox regression analyses were performed. RESULTS: In 693 KTR (57% men, 53 ± 13 years, estimated glomerular filtration rate [eGFR] 52 ± 20 mL/min/1.73 m2), baseline median urinary copper excretion was 23.6 (interquartile range 11.3-15.9) µg/24 h. Urinary protein excretion was positively associated with urinary copper excretion (standardized ß = 0.39, p < 0.001), and urinary copper excretion was positively associated with u-LFABP (standardized ß = 0.29, p < 0.001). During a median follow-up of 8 years, 109 (16%) KTR developed graft failure. KTR with relatively high copper excretion were at higher risk of long-term graft failure (hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 1.32-1.86 per log2, p < 0.001), independent of multiple potential confounders like eGFR, urinary protein excretion, and time after transplantation. A dose-response relationship was observed over increasing tertiles of copper excretion (HR: 5.03, 95% CI: 2.75-9.19, tertile 3 vs. 1, p < 0.001). u-LFABP was a significant mediator of this association (74% of indirect effect, p < 0.001). CONCLUSION: In KTR, urinary protein excretion is positively correlated with urinary copper excretion. In turn, higher urinary copper excretion is associated with an independent increased risk of kidney graft failure, with a substantial mediating effect through oxidative tubular damage. Further studies are warranted to investigate whether copper excretion-targeted interventions could improve kidney graft survival.

Low selenium intake is associated with risk of all-cause mortality in kidney transplant recipients.

BACKGROUND: Deficiency of the essential trace element selenium is common in kidney transplant recipients (KTR), potentially hampering antioxidant and anti-inflammatory defence. Whether this impacts the long-term outcomes of KTR remains unknown. We investigated the association of urinary selenium excretion, a biomarker of selenium intake, with all-cause mortality; and its dietary determinants. METHODS: In this cohort study, outpatient KTR with a functioning graft for longer than 1 year were recruited (2008-11). Baseline 24-h urinary selenium excretion was measured by mass spectrometry. Diet was assessed by a 177-item food frequency questionnaire, and protein intake was calculated by the Maroni equation. Multivariable linear and Cox regression analyses were performed. RESULTS: In 693 KTR (43% men, 52 ± 12 years), baseline urinary selenium excretion was 18.8 (interquartile range 15.1-23.4) µg/24-h. During a median follow-up of 8 years, 229 (33%) KTR died. KTR in the first tertile of urinary selenium excretion, compared with those in the third, had over a 2-fold risk of all-cause mortality [hazard ratio 2.36 (95% confidence interval 1.70-3.28); P < .001], independent of multiple potential confounders including time since transplantation and plasma albumin concentration. The most important dietary determinant of urinary selenium excretion was protein intake (Standardized ß 0.49, P < .001). CONCLUSIONS: Relatively low selenium intake is associated with a higher risk of all-cause mortality in KTR. Dietary protein intake is its most important determinant. Further research is required to evaluate the potential benefit of accounting for selenium intake in the care of KTR, particularly among those with low protein intake.

Plasma Copper Concentration Is Associated with Cardiovascular Mortality in Male Kidney Transplant Recipients.

Kidney transplant recipients (KTR) are at increased risk of cardiovascular mortality. We investigated whether, in KTR, post-transplantation copper status is associated with the risk of cardiovascular mortality and potential effect modification by sex. In this cohort study, plasma copper was measured using mass spectrometry in extensively-phenotyped KTR with a functioning allograft >1-year. Cox regression analyses with the inclusion of multiplicative interaction terms were performed. In 660 KTR (53 ± 13 years old, 56% male), the median baseline plasma copper was 15.42 (IQR 13.53-17.63) µmol/L. During a median follow-up of 5 years, 141 KTR died, 53 (38%) due to cardiovascular causes. Higher plasma copper was associated with an increased risk of cardiovascular mortality in the overall KTR population (HR 1.37; 95% CI, 1.07-1.77 per 1-SD, p = 0.01). Sex was a significant effect modifier of this association (Pinteraction = 0.01). Among male KTR, higher plasma copper concentration was independently associated with a two-fold higher risk of cardiovascular mortality (HR 2.09; 95% CI, 1.42-3.07 per 1-SD, p < 0.001). Among female KTR, this association was absent. This evidence offers a rationale for considering a sex-specific assessment of copper's role in cardiovascular risk evaluation. Further studies are warranted to elucidate whether copper-targeted interventions may decrease cardiovascular mortality in male KTR.

Low Sodium Intake, Low Protein Intake, and Excess Mortality in an Older Dutch General Population Cohort: Findings in the Prospective Lifelines-MINUTHE Study.

Background: Several studies have found a U-shaped association between sodium intake and mortality. The increased mortality risk of low sodium intake has raised debates and hampers widespread acceptance of public health campaigns and dietary guidelines on reducing sodium intake. Whether the excess risk can be attributed to low sodium intake alone or concomitant inadequate intake of other relevant nutrients is unknown. Objective: We investigated whether concomitant low protein intake could explain the lower part of the U-shaped association of sodium intake with all-cause mortality. Methods: We included 1603 individuals aged between 60 and 75 years old from the gender- and socioeconomic status-balanced prospective Lifelines-MINUTHE cohort study. Using multivariable Cox regression analyses, we investigated the association of sodium intake (24 h urinary sodium excretion) with all-cause mortality, including the interaction with protein intake calculated from the Maroni formula. Results: Mean intakes of sodium and protein were 3.9 ± 1.6 g/day and 1.1 ± 0.3 g/kg/day, respectively. After a median follow-up of 8.9 years, 125 individuals (7.8%) had died. The proportion of participants with insufficient protein intake (<0.8 g/kg/day) was inversely related to sodium intake (i.e., 23.3% in Q1 versus 2.8% in Q4, p < 0.001). We found an increased risk for mortality in both the highest quartile (Q4, >4.7 g/day; hazard ratio (HR) 1.74 (95% confidence interval (CI) 1.03−2.95)) and the lowest two quartiles of sodium intake (Q1, 0.7−2.8 g/day; 2.05 (1.16−3.62); p = 0.01 and Q2, 2.8−3.6 g/day; 1.85 (1.08−3.20); p = 0.03), compared with the third quartile of sodium intake (Q3, 3.6−4.7 g/day). This U-shaped association was significantly modified by protein intake (Pinteraction = 0.006), with the increased mortality risk of low sodium intake being reversed to the lowest mortality risk with concomitant high protein intake. In contrast, the increased mortality risk of low sodium intake was magnified by concomitant low protein intake. Conclusions: We found that a higher protein intake counteracts the increased mortality risk observed in subjects with a low sodium intake. In contrast, a joint low intake of sodium and protein is associated with an increased mortality risk, allegedly due to poor nutritional status. These findings support the guidelines that advocate a lower sodium intake, while highlighting the importance of recognizing overall nutritional status among older adults.

Long-term cognitive impairments in kidney transplant recipients: impact on participation and quality of life.

BACKGROUND: Cognitive impairment is often present shortly after transplantation in kidney transplant recipients (KTR). To date, it is unknown whether these impairments persist in thelong term, to what extent they are associated with disease-related variables and whether they affect societal participation and quality of life (QoL) of KTR. METHOD: This study was part of the TransplantLines Biobank & Cohort Study in the University Medical Center Groningen. A total of 131 KTR, with a mean age of 53.6 years (SD = 13.5) transplanted ≥1 year ago (M = 11.2 years, range 1-41.7 years), were included and compared with 306 healthy controls (HC). KTR and HC were well matched; there were no significant differences regarding age, sex and education. All participants were assessed with neuropsychological tests measuring memory, mental speed, attention and executive functioning, and with questionnaires examining societal participation and QoL. RESULTS: Compared with HC, KTR performed significantly worse on memory, mental speed and measures of executive functioning (all P-values <0.05). Moreover, 16% of KTR met the criteria for mild cognitive impairment (MCI), compared with 2.6% of the HC. MCI in KTR was not significantly correlated with age- and disease-related variables. Poorer cognitive functioning was significantly related to lower levels of societal participation and to lower QoL (all P-values <0.01). CONCLUSIONS: This study shows long-term cognitive impairments in KTR, which are not related to disease-related variables. Neuropsychological assessment is important to timely signal these impairments, given their serious negative impact on societal participation and QoL.

Frailty and risk of hospitalization from COVID-19 infection among older adults: evidence from the Dutch Lifelines COVID-19 Cohort study.

BACKGROUND: Frailty is associated with COVID-19 severity in clinical settings. No general population-based studies on the association between actual frailty status and COVID-19 hospitalization are available. AIMS: To investigate the association between frailty and the risk of COVID-19 hospitalization once infected. METHODS: 440 older adults who participated in the Lifelines COVID-19 Cohort study in the Northern Netherlands and reported positive COVID-19 testing results (54.2% women, age 70 ± 4 years in 2021) were included in the analyses. COVID-19 hospitalization status was self-reported. The Groningen Frailty Indicator (GFI) was derived from 15 self-reported questionnaire items related to daily activities, health problems, and psychosocial functioning, with a score ≥ 4 indicating frailty. Both frailty and COVID-19 hospitalization were assessed in the same period. Poisson regression models with robust standard errors were used to analyze the associations between frailty and COVID-19 hospitalization. RESULTS: Of 440 older adults included, 42 were hospitalized because of COVID-19 infection. After adjusting for sociodemographic and lifestyle factors, a higher risk of COVID-19 hospitalization was observed for frail individuals (risk ratio (RR) [95% CI] 1.97 [1.06-3.67]) compared to those classified as non-frail. DISCUSSION: Frailty was positively associated with COVID-19 hospitalization once infected, independent of sociodemographic and lifestyle factors. Future research on frailty and COVID-19 should consider biomarkers of aging and frailty to understand the pathophysiological mechanisms and manifestations between frailty and COVID-19 outcomes. CONCLUSIONS: Frailty was positively associated with the risk of hospitalization among older adults that were infected with COVID-19. Public health strategies for frailty prevention in older adults need to be advocated, as it is helpful to reduce the burden of the healthcare system, particularly during a pandemic like COVID-19.

Employment Status and Work Functioning among Kidney Transplant Recipients.

BACKGROUND AND OBJECTIVES: To date, employment figures of kidney transplant recipients in Europe are inconsistent. Additionally, little is known about work functioning of employed kidney transplant recipients and work functioning trajectories before and after transplantation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data from the ongoing TransplantLines Biobank and Cohort study and from community-dwelling employed adults were used. Health-related work functioning of kidney transplant recipients was assessed with the Work Role Functioning Questionnaire 2.0 and compared with potential kidney donors and community-dwelling employed adults. RESULTS: We included 668 kidney transplant recipients of working age (59% men, age 51±11 years) at median 3 (interquartile range, 2-10) years after transplantation, 246 potential kidney donors of working age (43% men, age 53±9 years), and 553 community-dwelling employed adults (70% men, age 45±11 years). The proportion of employed kidney transplant recipients was lower compared with potential kidney donors (56% versus 79%). If employed, the work functioning score of kidney transplant recipients was slightly lower compared with employed potential kidney donors yet higher compared with community-dwelling employed adults (medians 91 [interquartile range, 76-98], 94 [interquartile range, 85-99], and 88 [interquartile range, 79-95], respectively). Backward linear regression analyses revealed that lower educational level, having a kidney from a deceased donor, presence of tingling or numbness of hands or feet, presence of concentration/memory problems, presence of anxiety, and presence of severe fatigue were independently associated with lower work functioning among kidney transplant recipients. Additional subgroup analyses showed that work functioning scores were lower before transplantation than at 12 months after transplantation (83 [interquartile range, 66-93] versus 92 [interquartile range, 88-98], respectively; P=0.002). CONCLUSIONS: Stable employed kidney transplant recipients report to function well at work. In addition, this study shows that self-reported work functioning is higher after successful kidney transplantation compared with before transplantation. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: TransplantLines Biobank and Cohort study, NCT03272841 PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_09_26_CJN05560522.mp3.

Long-term health-related quality of life, healthcare utilisation and back-to-work activities in intensive care unit survivors: Prospective confirmatory study from the Frisian aftercare cohort.

PURPOSE: More substantial information on recovery after Intensive Care Unit (ICU) admission is urgently needed. In a previous retrospective study, the proportion of non-recovery patients was 44%. The aim of this prospective follow-up study was to evaluate changes in Health-Related Quality of Life (HRQoL) in the first year after ICU-admission. METHODS: Long-stay adult ICU-patients (≥ 48 hours) were included. HRQoL was evaluated with the Dutch translation of the RAND-36 item Health Survey (RAND-36) at baseline via proxy measurement, and at three, six, and twelve months after ICU admission. Subsequently, the relation between physical functioning, healthcare utilisation, and work activities was explored. RESULTS: A total of 81 patients were included in this study. Fifty-five percent of patients did not meet criteria for full recovery and were allocated to the Non Recovery (NR)-group (Physical Functioning domain-score: 35 [15-55]). Baseline physical HRQoL differed significantly between the Recovery (R) and NR-group. Patients in the NR-group received home care more often and had higher healthcare utilisation (44 versus 17% in the first three months post-ICU, p = 0.013). Only fourteen percent of NR-patients were able to participate in work activities. Moreover, NR-patients persistently showed impaired overall HRQoL throughout the year after critical illness. CONCLUSIONS: Limited recovery in ICU survivors is reflected in overall impaired HRQoL, as well as in far-reaching consequences for patients' healthcare needs and their ability to reintegrate into society. In our study, baseline HRQoL appeared to be an important predictor of long-term outcomes, but not Clinical Frailty Scale (CFS) score. And, (proxy-derived) HRQoL may help to identify patients at risk of long-term non-recovery.

Circulating de novo lipogenesis fatty acids and all-cause mortality in a prospective Dutch population cohort.

BACKGROUND: Circulating fatty acids (FA) from de novo lipogenesis (DNL) are associated with all-cause mortality in individuals with elevated CVD risk. However, compared to FA early in the DNL synthetic pathway, cis-vaccenic acid, one of the FA distal in the DNL synthetic pathway, has rarely been studied in a general population cohort. We hypothesized that circulating cis-vaccenic acid is more strongly related to all-cause mortality than other circulating DNL-related FA. OBJECTIVES: The primary and secondary objectives of this study were to investigate the prospective associations of plasma levels of cis-vaccenic acid and other DNL-related FA with all-cause mortality in a general population, respectively. METHODS: We included 850 participants (mean ± SD age 53 ± 15 years) from the Dutch Lifelines cohort study. Circulating levels of palmitic (C16:0), palmitoleic (C16:1n7), cis-vaccenic (cis-C18:1n7), stearic (C18:0), oleic acid (C18:1n9) in plasma phospholipids (PL) and triglycerides (TG) were measured by gas chromatography. The associations of circulating cis-C18:1n7 and other DNL-related FA with all-cause mortality were assessed using Cox regression analyses. RESULTS: During a median follow-up of 9.3 (IQR: 5.4-10.8) years, 34 (4.0%) participants had died. In plasma PL, a 1-SD increase in cis-C18:1n7 was associated with an increased risk of all-cause mortality in univariate and multivariate models (p<0.02 for all), with a HR [95% CI] of 1.60 [1.13-2.25] after adjustment for age and sex. CONCLUSIONS: Circulating plasma PL cis-C18:1n7 was associated with a higher risk for all-cause mortality. More studies are needed in different cohorts to verify and validate our results.

Associations of 24 h urinary excretions of α- and γ-carboxyethyl hydroxychroman with plasma α- and γ-tocopherol and dietary vitamin E intake in older adults: the Lifelines-MINUTHE Study.

BACKGROUND: Urinary metabolites of vitamin E, i.e., α- and γ-carboxyethyl hydroxychroman (α- and γ-CEHC), have gained increasing attention and have been proposed as novel biomarkers of vitamin E intake and status. However, there are insufficient data on the relationship of plasma α-tocopherol and γ-tocopherol and dietary vitamin E intake with 24 h urinary excretions of α- and γ-CEHC. OBJECTIVES: We aimed to (1) investigate the associations of urinary α- and γ-CEHC/creatinine ratios and 24 h urinary excretions of α- and γ-CEHC with plasma α- and γ-tocopherol, respectively; (2) investigate the associations of urinary α- and γ-CEHC/creatinine ratios and 24 h urinary excretions of α- and γ-CEHC with dietary vitamin E intake, and we hypothesize that 24 h urinary excretions of α- and γ-CEHC will better correlate with vitamin E intake than urinary α- and γ-CEHC/creatinine ratios. DESIGN: 24 h Urine and plasma samples were collected from 1519 participants (60-75 years, male: 50%) included in the Lifelines-MINUTHE Study for the assessments of urinary α- and γ-CEHC/creatinine ratios and 24 h urinary excretions of α- and γ-CEHC, and plasma α- and γ-tocopherol. Among those participants, dietary vitamin E intake data from 387 participants were available from an externally validated Flower-Food Frequency Questionnaire (FFQ). The associations of plasma α- and γ-tocopherol, dietary vitamin E intake, with urinary α- and γ-CEHC were assessed using multivariate linear regressions. RESULTS: 24 h Urinary excretion of α-CEHC (median (IQR): 0.9 (0.3-2.4) µmol) was less than that of γ-CEHC (median (IQR): 1.5 (0.5-3.5) µmol). After adjustment for covariates, we found that 24 h urinary α-CEHC excretion and urinary α-CEHC/creatinine ratio were both positively associated with plasma α-tocopherol (std.beta: 0.06, p = 0.02; std.beta: 0.06, p = 0.01, respectively). Furthermore, the sum of 24 h urinary α- and γ-CEHC excretions was positively associated with dietary vitamin E intake (std.beta: 0.08; p = 0.03), whereas there was no relation between urinary α- and γ-CEHC/creatinine ratios and vitamin E intake. No association was observed neither between plasma α- and γ-tocopherol and dietary vitamin E intake, nor between urinary γ-CEHC and plasma γ-tocopherol. CONCLUSION: Our study confirmed our hypothesis that 24 h urinary α- and γ-CEHC excretions would be a better marker for dietary vitamin E intake than urinary α- and γ-CEHC/creatinine ratios. Considering that both 24 h urinary α- and γ-CEHC excretions and α- and γ-CEHC/creatinine ratios were also associated with plasma α-tocopherol status, we suggest that 24 h urinary α- and γ-CEHC excretions could be used to assess overall vitamin E status.

Ultra-processed foods and risk of all-cause mortality in renal transplant recipients.

BACKGROUND: Renal transplant recipients (RTRs) have a 6-fold higher risk of mortality than age- and sex-matched controls. Whether high consumption of ultra-processed foods is associated with survival in RTRs is unknown. OBJECTIVES: We aimed to study the association between high consumption of ultra-processed foods and all-cause mortality in stable RTRs. METHODS: We conducted a prospective cohort study in adult RTRs with a stable graft. Dietary intake was assessed using a validated 177-item FFQ. Food items were categorized according to the NOVA classification system and the proportion ultra-processed foods comprised of total food weight per day was calculated. RESULTS: We included 632 stable RTRs (mean ± SD age: 53.0 ± 12.7 y, 57% men). Mean ± SD consumption of ultra-processed foods was 721 ± 341 g/d (28% of total weight of food intake), whereas the intake of unprocessed and minimally processed foods, processed culinary ingredients, and processed foods accounted for 57%, 1%, and 14%, respectively. During median follow-up of 5.4 y [IQR: 4.9-6.0 y], 129 (20%) RTRs died. In Cox regression analyses, ultra-processed foods were associated with all-cause mortality (HR per doubling of percentage of total weight: 2.13; 95% CI: 1.46, 3.10; P < 0.001), independently of potential confounders. This association was independent from the quality of the overall dietary pattern, expressed by the Mediterranean Diet Score (MDS) or Dietary Approaches to Stop Hypertension (DASH) score. When analyzing ultra-processed foods by groups, only sugar-sweetened beverages (HR: 1.21; 95% CI: 1.05, 1.39; P = 0.007), desserts (HR: 1.24; 95% CI: 1.02, 1.49; P = 0.03), and processed meats (HR: 1.87; 95% CI: 1.22, 2.86; P = 0.004) were associated with all-cause mortality. CONCLUSIONS: Consumption of ultra-processed foods, in particular sugar-sweetened beverages, desserts, and processed meats, is associated with a higher risk of all-cause mortality after renal transplantation, independently of low adherence to high-quality dietary patterns, such as the Mediterranean diet and the DASH diet.This trial was registered at clinicaltrials.gov as NCT02811835.

The influence of the dietary exposome on oxidative stress in pregnancy complications.

Pregnancy complications including fetal growth restriction, preeclampsia, and preterm birth, as well as gestational diabetes, affect one in every four to five pregnancies. Accumulating evidence indicates that increased production of reactive oxygen species accompanies these complications. Given that reactive oxygen species are cell stress-inducing agents, they may have a causal role in disease pathophysiology, although the exact mechanisms by which they contribute to pregnancy complications are not completely understood. Since many environmental and lifestyle factors and exposures are known to modulate reactive oxygen species production, the exposome of pregnant women could contribute to increased generation of reactive oxygen species. The objective of this review is to provide a comprehensive overview of the endogenous and exogenous exposome factors that regulate reactive species in healthy and complicated pregnancies. We also provide a description of dietary interventions aimed at the reduction of reactive species in order to attenuate adverse pregnancy outcome. Dietary interventions in general hold minimal risk in pregnancy and could therefore be considered a promising therapeutic approach.

Ultraprocessed food consumption and kidney function decline in a population-based cohort in the Netherlands.

BACKGROUND: Ultraprocessing makes food products more convenient, appealing, and profitable. Recent studies show that high ultraprocessed food (UPF) intake is associated with cardiometabolic diseases. OBJECTIVES: The aim of this study is to investigate the association between UPF consumption and risks of kidney function decline in the general population. METHODS: In a prospective, general population-based Lifelines cohort from Northern Netherlands, 78,346 participants free of chronic kidney disease (CKD) at baseline responded to a 110-item FFQ. We used a multivariable regression analysis to study the associations of the proportion (in grams/day) of UPFs in the total diet with a composite kidney outcome [incident CKD or a ≥30% estimated glomerular filtration rate (eGFR) decline relative to baseline] and annual change in eGFR. RESULTS: On average, 37.7% of total food intake came from UPFs. After 3.6 ± 0.9 years of follow-up, 2470 participants (3.2%) reached the composite kidney outcome. Participants in the highest quartile of UPF consumption were associated with a higher risk of the composite kidney outcome (OR, 1.27; 95% CI, 1.09-1.47; P = 0.003) compared with those in the lowest quartile, regardless of their macro- or micronutrient intake or diet quality. Participants in the highest quartile had a more rapid eGFR decline (ß, -0.17; 95% CI, -0.23 to -0.11; P < 0.001) compared with those in the lowest quartile. Associations were generally consistent across different subgroups. CONCLUSIONS: Higher UPF consumption was associated with a higher risk of a composite kidney outcome (incident CKD or ≥30% eGFR decline) and a more rapid eGFR decline in the general population, independent of confounders and other dietary indices.