Longitudinal NGAL and cystatin C plasma profiles present a high level of heterogeneity in a mixed ICU population.

BACKGROUND: NGAL and Cystatin C (CysC) as biomarkers for the early detection of AKI are subject to both pathophysiological, as well as patient related heterogeneity. The aim of this study was to investigate the timeline of plasma levels of NGAL and CysC during the first seven days of ICU admission in a mixed ICU population and to relate these to AKI severity during ICU stay. Via these means we aimed to bring clarity to the previously reported heterogeneity of these renal biomarkers. METHODS: Prospective Observation Cohort. Consecutive patients admitted to adult ICU at an academic hospital in the Netherlands between 18-02-2014 and 31-03-2014 were included. Urine output, serum creatinine, plasma NGAL and CysC were recorded during the first seven days of ICU admission. Biomarker expression was analyzed based on KDIGO score and time of AKI diagnosis. RESULTS: 335 patients were included, 110 met KDIGO criteria for AKI. NGAL and CysC plasma levels were higher in AKI patients compared to non-AKI, high variability in individual values resulted in 56% of AKI patients having a false negative, and 32% of non-AKI patients having a false positive. Individual biomarker levels were variable, and no pattern based on KDIGO score was observed. CONCLUSIONS: Plasma NGAL and CysC as biomarkers for the early AKI detection may be subject to pathophysiological, and patient related heterogeneity. Further understanding of individual biomarker profiles may help in their application amongst mixed ICU populations. TRIAL REGISTRATION: The need for informed consent was waived by the Institutional Ethical Review Board of the University Medical Center Groningen (METc 2013 - 174) by Prof. dr. W.A. Kamps on May 17th 2013.

Muscle mass and estimates of renal function: a longitudinal cohort study.

BACKGROUND: Creatinine is the most widely used test to estimate the glomerular filtration rate (GFR), but muscle mass as key determinant of creatinine next to renal function may confound such estimates. We explored effects of 24-h height-indexed creatinine excretion rate (CER index) on GFR estimated with creatinine (eGFRCr ), muscle mass-independent cystatin C (eGFRCys ), and the combination of creatinine and cystatin C (eGFRCr-Cys ) and predicted probabilities of discordant classification given age, sex, and CER index. METHODS: We included 8076 adults enrolled in the PREVEND study. Discordant classification was defined as not having eGFRCr  <60 mL/min per 1.73 m2 when eGFRCys was <60 mL/min/1.73 m2 . Baseline effects of age and sex on CER index were quantified with linear models using generalized least squares. Baseline effects of CER index on eGFR were quantified with quantile regression and logistic regression. Effects of annual changes in CER index on trajectories of eGFR were quantified with linear mixed-effects models. Missing observations in covariates were multiply imputed. RESULTS: Mean (SD) CER index was 8.0 (1.7) and 6.1 (1.3) mmol/24 h per meter in male and female participants, respectively (Pdifference  < 0.001). In male participants, baseline CER index increased until 45 years of age followed by a gradual decrease, whereas a gradual decrease across the entire range of age was observed in female participants. For a 70-year-old male participant with low muscle mass (CER index of 2 mmol/24 h per meter), predicted baseline eGFRCr and eGFRCys disagreed by 24.7 mL/min/1.73 m2 (and 30.1 mL/min/1.73 m2 when creatinine was not corrected for race). Percentages (95% CI) of discordant classification in male and female participants aged 60 years and older with low muscle mass were 18.5% (14.8-22.1%) and 15.2% (11.4-18.5%), respectively. For a 70-year-old male participant who lost muscle during follow-up, eGFRCr and eGFRCys disagreed by 1.5, 5.0, 8.5, and 12.0 mL/min/1.73 m2 (and 6.7, 10.7, 13.5, and 15.9 mL/min/1.73 m2 when creatinine was not corrected for race) at baseline, 5 years, 10 years, and 15 years of follow-up, respectively. CONCLUSIONS: Low muscle mass may cause considerable overestimation of single measurements of eGFRCr . Muscle wasting may cause spurious overestimation of repeatedly measured eGFRCr . Implementing muscle mass-independent markers for estimating renal function, like cystatin C as superior alternative to creatinine, is crucial to accurately assess renal function in settings of low muscle mass or muscle wasting. This would also eliminate the negative consequences of current race-based approaches.

Kidney Function in Patients With Neuromuscular Disease: Creatinine Versus Cystatin C.

Background: Accurate measurement of kidney function in patients with neuromuscular disorders is challenging. Cystatin C, a marker not influenced by skeletal muscle degradation, might be of clinical value in these patients. Methods: We consecutively enrolled 39 patients with neuromuscular disorders. We investigated the association of the eGFR, based on plasma creatinine and Cystatin C, with clinical and biochemical variables associated with kidney function, namely age and galectin-3. Results: Creatinine-based eGFR was 242 (±80) and Cystatin C-based eGFR was 110 (±23) mL/min/1.73 m2. Cystatin C-based eGFR was associated with age (ß -0.63 p < 0.0001) and galectin-3 levels (ß -0.43 p < 0.01), while creatinine-based eGFR was not (ß -0.22 p = 0.20; ß -0.28 p = 0.10). Sensitivity analyses in Duchenne and Becker patients revealed the same results: Cystatin C-based eGFR was associated with age (ß -0.61 p < 0.01) and galectin-3 levels (ß -0.43 p = 0.05), while creatinine-based eGFR was not (ß -0.32 p = 0.13; ß -0.34 p = 0.14). Conclusions: These data indicate that estimation of renal function in patients with neuromuscular disorders cannot reliably be achieved with creatinine, while Cystatin C appears a reasonable alternative. Since a large proportion of patients with neuromuscular disorders develops heart failure, and requires heart failure medication, adequate monitoring of renal function is warranted.

Net Endogenous Acid Excretion and Kidney Allograft Outcomes.

BACKGROUND AND OBJECTIVES: High dietary acid load may accelerate a decline in kidney function. We prospectively investigated whether dietary acid load is associated with graft outcomes in kidney transplant recipients, and whether venous bicarbonate mediates this association. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used data from 642 kidney transplant recipients with a functioning graft ≥1 year after transplantation. Net endogenous acid production was estimated using food frequency questionnaires and, alternatively, 24-hour urinary urea and potassium excretion to estimate net endogenous acid production. We defined the composite kidney end point as a doubling of plasma creatinine or graft failure. Multivariable Cox regression analyses, adjusted for potential confounders, were used to study the associations of dietary acid load with the kidney end point. We evaluated potential mediation effects of venous bicarbonate, urinary bicarbonate excretion, urinary ammonium excretion, titratable acid excretion, and net acid excretion on the association between net endogenous acid production and the kidney end point. RESULTS: The median net endogenous acid production using food frequency questionnaires and net endogenous acid production using urinary excretion were 40 (interquartile range, 35-45) and 54 (interquartile range, 44-66) mEq/day, respectively. During a median follow-up of 5.3 years (interquartile range, 4.1-6.0), 121 (19%) participants reached the kidney end point. After multivariable adjustment, net endogenous acid production using food frequency questionnaires and net endogenous acid production using urinary excretion (per SD higher) were independently associated with higher risk for kidney end point (hazard ratio, 1.33; 95% confidence interval, 1.12 to 1.57, P=0.001 and hazard ratio, 1.44; 95% confidence interval, 1.24 to 1.69, P<0.001, respectively). Baseline venous bicarbonate mediated 20% of the association between net endogenous acid production using food frequency questionnaires and the kidney end point. Baseline venous bicarbonate, urinary ammonium excretion, and net acid excretion mediated 25%, -14%, and -18%, respectively, of the association between net endogenous acid production using urinary excretion and the kidney end point. CONCLUSIONS: Higher dietary acid load was associated with a higher risk of doubling of plasma creatinine or graft failure, and this association was partly mediated by venous bicarbonate, urinary ammonium, and net acid excretion.

Self-reported alcohol consumption, carbohydrate deficient transferrin and risk of cardiovascular disease: The PREVEND prospective cohort study.

BACKGROUND: Self-reported alcohol consumption is an established risk factor for cardiovascular disease (CVD). Carbohydrate deficient transferrin (CDT) is an established objective marker of excessive alcohol consumption, but data on its prospective association with CVD are lacking. We aimed to evaluate the associations of self-reported alcohol consumption and CDT (expressed as %CDT, a more reliable marker than absolute CDT levels) with CVD risk. MATERIALS AND METHODS: In the PREVEND prospective study of 5,206 participants (mean age, 53 years; 47.7% males), alcohol consumption by self-reports, absolute CDT measured using the Siemens nephelometric assay and %CDT calculated as the percentage of total transferrin concentrations, were assessed at baseline. Alcohol consumption was classified into 5 categories: abstention (reference), light, light-moderate, moderate and heavy alcohol consumption.Hazard ratios (HRs) (95% confidence intervals [CI]) for first CVD events were estimated. RESULTS: Mean (SD) of %CDT was 1.59 (0.54) %. During a median follow-up of 8.3 years, 326 first CVD events were recorded. Compared with abstainers, the multivariable-adjusted HRs (95% CIs) of CVD for light, light-moderate, moderate and heavy alcohol consumption were 0.66 (0.46-0.95), 0.83 (0.62-1.11), 0.83 (0.61-1.14) and 0.80 (0.48-1.36), respectively. Light alcohol consumption was associated with reduced coronary heart disease risk 0.62 (0.40-0.96), whereas light-moderate alcohol consumption was associated with reduced stroke risk 0.45 (0.24-0.83). The association of %CDT with CVD risk was not significant. CONCLUSIONS: Our findings confirm the established association between self-reported light to moderate alcohol consumption and reduced CVD risk. However, %CDT within the normal reference range may not be a risk indicator for CVD.

Interpretation of Folate Results in Hemolytic Plasma Samples: A Practical Approach.

Folate analysis in plasma is affected by hemolysis, which can lead to biased results. However, the degree of hemolysis that is considered acceptable is unclear. We explored the relationship between folate concentration and degree of hemolysis. Heparin plasma samples (N=77, hemolysis index ≤10 µmol/L) were spiked with increasing amounts of corresponding patient-specific hemolysate. Subsequently, the folate concentration and hemolysis index were measured using two Roche Cobas platforms, and their incremental relationship was investigated. The folate concentration ranged from 2.9 to 30.9 nmol/L with a median (interquartile range) of 11.4 (8.6-19.1) nmol/L. The linear relationship between the increments in folate concentration and hemolysis index was approximated by the function y=1.86x+1.56 (R2=0.996), where x represents the laboratory-specific critical difference in folate concentration, which can be calculated from the analytical variation of the employed folate assay(s), and y represents the hemolysis threshold. The hemolysis threshold did not significantly differ between the tertiles of plasma folate concentration (P=0.10). In conclusion, we have provided an evidence-based approach that can be used to reliably interpret folate concentrations in hemolytic samples, independent of the patient's folate status.

Age dependency of plasma vitamin B12 status markers in Dutch children and adolescents.

BACKGROUND: Vitamin B12 deficiency in children may be associated with (severe) neurological manifestations, therefore recognition is important. Diagnosing vitamin B12 deficiency in children is challenging. This study aimed to investigate plasma methylmalonic acid, holotranscobalamin, and total cobalamin in children 0-18 years of age and to estimate age-dependent reference intervals. METHODS: Plasma vitamin B12 markers were measured in collected plasma samples of 170 children 0-18 years visiting a local primary care laboratory. All had within-reference hemoglobin and MCV values. Pediatric plasma vitamin B12 biomarkers were measured and reference values were derived thereof. RESULTS: Plasma methylmalonic acid was higher in young children, in particular between 1 and 6 months of age; total cobalamin and holotranscobalamin were highest from 0.5 to 4 years and decreased till 10 years of age. Plasma holotranscobalamin was highly correlated with plasma total cobalamin; their ratio was independent of age. Plasma methylmalonic acid was slightly more related to total cobalamin than to holotranscobalamin. A large proportion of mainly young children would be misclassified when adult references are applied. CONCLUSIONS: Pediatric reference values for cobalamin markers are necessary to allow for early recognition and monitoring of children suspect of (clinical) cobalamin deficiency. IMPACT: We analyzed three plasma vitamin B12 status markers, i.e., total cobalamin, holotranscobalamin, and methylmalonic acid, in the plasma of 170 children 0-18 years of age and were able to derive reference intervals thereof. Recognition of vitamin B12 deficiency in children is important but challenging as pediatric reference intervals for plasma vitamin B12 status markers, particularly plasma holotranscobalamin, are not well described. We think that our results may help early recognition and monitoring of children suspect of (clinical) vitamin B12 deficiency.

Thyroid function and risk of all-cause and cardiovascular mortality: a prospective population-based cohort study.

PURPOSE: Although thyroid hormones are irrefutably implicated in cardiovascular physiology, the impact of within-reference range variations of thyroid function on cardiovascular disease (CVD) remains unclear. Elucidating this is important, since it could foster preventive treatment and reduce global CVD burden. We therefore investigated the impact of within-reference range variations of thyroid function on all-cause and cardiovascular mortality. METHODS: We included community-dwelling individuals aged 28-75 years from a prospective cohort study, without known use of thyroid-affecting therapy and with thyrotropin within reference range. Associations of thyroid function with mortality were quantified using Cox models and adjusted for sociodemographic and cardiovascular risk factors. RESULTS: Mean (SD) age of the 6,054 participants (52.0% male) was 53.3 (12.0) years. During 47,594 person-years of follow-up, we observed 380 deaths from all causes and 103 from CVDs. Although higher thyrotropin was not associated with all-cause mortality (adjusted HR 1.02, 95% CI 0.92-1.14), point estimates for cardiovascular mortality diverged toward increased risk in younger (<72 years) participants (1.31, 1.00-1.72) and decreased risk in elderly (≥72 years) (0.77, 0.56-1.06). Higher free thyroxine (FT4) was associated with all-cause mortality (1.18, 1.07-1.30) and with cardiovascular mortality only in elderly (1.61, 1.19-2.18), but not in younger participants (1.03, 0.78-1.34). Higher free triiodothyronine (FT3) was associated with all-cause mortality in females only (1.18, 1.02-1.35). FT3 was not associated with cardiovascular mortality (0.91, 0.70-1.18). CONCLUSIONS: Community-dwelling elderly individuals with high-normal thyroid function are at increased risk of all-cause and cardiovascular mortality, reinforcing the need of redefining the current reference ranges of thyroid function.

Methylmalonic acid, vitamin B12, renal function, and risk of all-cause mortality in the general population: results from the prospective Lifelines-MINUTHE study.

BACKGROUND: Methylmalonic acid (MMA) is best known for its use as a functional marker of vitamin B12 deficiency. However, MMA concentrations not only depend on adequate vitamin B12 status, but also relate to renal function and endogenous production of propionic acid. Hence, we aimed to investigate to what extent variation in MMA levels is explained by vitamin B12 and eGFR and whether MMA levels are associated with mortality if vitamin B12 and eGFR are taken into account. METHODS: A total of 1533 individuals (aged 60-75 years, 50% male) were included from the Lifelines Cohort and Biobank Study. Individuals were included between 2006 and 2013, and the total follow-up time was 8.5 years. RESULTS: Median [IQR] age of the study population was 65 [62-69] years, 50% was male. At baseline, median MMA concentration was 170 [138-216] nmol/L, vitamin B12 290 [224-362] pmol/L, and eGFR 84 [74-91] mL/min/1.73 m2. Log2 vitamin B12, log2 eGFR, age, and sex were significantly associated with log2 MMA in multivariable linear regression analyses (model R2 = 0.22). After a total follow-up time of 8.5 years, 72 individuals had died. Log2 MMA levels were significantly associated with mortality (hazard ratio [HR] 1.67 [95% CI 1.25-2.22], P < 0.001). Moreover, we found a significant interaction between MMA and eGFR with respect to mortality (Pinteraction < 0.001). CONCLUSIONS: Only 22% of variation in MMA levels was explained by vitamin B12, eGFR, age, and sex, indicating that a large part of variation in MMA levels is attributable to other factors (e.g., catabolism, dietary components, or gut microbial production). Higher MMA levels are associated with an increased risk for mortality, independent of vitamin B12, eGFR, and sex. This association was more pronounced in individuals with impaired renal function.

Vitamin Status and Diet in Elderly with Low and High Socioeconomic Status: The Lifelines-MINUTHE Study.

Socioeconomic health inequalities are an important global public health problem. However, it is not well known to what extent socioeconomic inequalities culminate in impaired vitamin status and whether this is mediated by diet. We, therefore, aimed to assess vitamin status in a population already at increased risk of micronutrient deficiency, i.e., elderly with high and low socioeconomic status (SES), and to investigate whether potential differences therein were mediated by diet quality. Vitamin status in 1605 individuals (60-75 years) from the Lifelines- Micronutrients and Health inequalities in Elderly (MINUTHE) Study was assessed by measuring folic acid and the vitamins B6, B12, D, A, E, and K. Multinomial logistic and linear regression analyses were applied to test the associations between SES and vitamin status. Mediation analysis was used to explore the interrelationship between SES, diet quality, and vitamin status. Low SES was associated with poorer status of vitamin B6, vitamin B12, and, notably, folic acid. Moreover, multivitamin deficiencies were more prevalent in the low SES group. Diet quality was found to mediate the associations of SES with folic acid (for 39.1%), vitamin B6 (for 37.1%), and vitamin B12 (for 37.2%). We conclude that low SES is a risk factor for a spectrum of vitamin deficiencies. Diet quality can partially explain the socioeconomic differences in vitamin status, suggesting that policymakers can mitigate socioeconomic inequality in nutritional status through improving diet quality.

Plasma C-Peptide and Risk of Developing Type 2 Diabetes in the General Population.

C-peptide measurement may represent a better index of pancreatic ß-cell function compared to insulin. While insulin is mainly cleared by liver, C-peptide is mainly metabolized by kidneys. The aim of our study was to evaluate the association between baseline plasma C-peptide level and the development of type 2 diabetes independent of glucose and insulin levels and to examine potential effect-modification by variables related to kidney function. We included 5176 subjects of the Prevention of Renal and Vascular End-Stage Disease study without type 2 diabetes at baseline. C-peptide was measured in plasma with an electrochemiluminescent immunoassay. Cox proportional hazards regression was used to evaluate the association between C-peptide level and type 2 diabetes development. Median C-peptide was 722 (566-935) pmol/L. During a median follow-up of 7.2 (6.0-7.7) years, 289 individuals developed type 2 diabetes. In multivariable-adjusted Cox regression models, we observed a significant positive association of C-peptide with the risk of type 2 diabetes independent of glucose and insulin levels (hazard ratio (HR): 2.35; 95% confidence interval (CI): 1.49-3.70). Moreover, we found significant effect modification by hypertension and albuminuria (p < 0.001 and p = 0.001 for interaction, respectively), with a stronger association in normotensive and normo-albuminuric subjects and absence of an association in subjects with hypertension or albuminuria. In this population-based cohort, elevated C-peptide levels are associated with an increased risk of type 2 diabetes independent of glucose, insulin levels, and clinical risk factors. Elevated C-peptide level was not independently associated with an increased risk of type 2 diabetes in individuals with hypertension or albuminuria.

High-Sensitivity Troponin-T and Cardiovascular Outcomes in the Community: Differences Between Women and Men.

OBJECTIVE: To evaluate associations of high-sensitivity cardiac troponin-T (cTnT) with cardiovascular disease (CVD), heart failure (HF), and mortality in community-dwelling women and men. PARTICIPANTS AND METHODS: A total of 8226 adults from the Prevention of Renal and Vascular End-stage Disease (PREVEND) cohort (1997-1998) were enrolled in a prospective observational study (mean age: 49 years; 50.2% women). Sex-specific associations of cTnT levels with future clinical outcomes were evaluated using adjusted Cox-regression models. RESULTS: Measurable cTnT levels (≥3 ng/L) were detected in 1102 women (26.7%) and in 2396 men (58.5%). Baseline cTnT levels were associated with a greater risk of developing CVD in women than men [Hazard ratio (HRwomen), 1.48 per unit increase in log2-cTnT; 95% CI, 1.21 to 1.81 vs HRmen, 1.20; 95% CI, 1.07 to 1.35; Pinteraction<.001]. Similar sex-related differences were observed for HF (Pinteraction= .005) and mortality (Pinteraction= .008). Further, compared with referent category (cTnT <3 ng/L), women with cTnT levels greater than or equal to 6 ng/L had a significantly increased risk for CVD (HR, 2.30; 95% CI, 1.45 to 3.64), HF (HR, 2.86; 95% CI, 1.41 to 5.80), and mortality (HR, 2.65; 95% CI, 1.52 to 4.61), whereas men with cTnT levels greater than or equal to 6 ng/L had a significantly increased risk only for CVD (HR, 1.51; 95% CI, 1.07 to 2.13). CONCLUSION: Baseline cTnT levels were associated with future CVD, HF, and mortality in both sexes, and these associations were stronger in women. Future studies are needed to determine the value of cTnT in early diagnosis of CVD, particularly in women.

High-Density Lipoprotein Particles and Their Relationship to Posttransplantation Diabetes Mellitus in Renal Transplant Recipients.

High concentrations of high-density lipoprotein (HDL) cholesterol are likely associated with a lower risk of posttransplantation diabetes mellitus (PTDM). However, HDL particles vary in size and density with yet unestablished associations with PTDM risk. The aim of our study was to determine the association between different HDL particles and development of PTDM in renal transplant recipients (RTRs). We included 351 stable outpatient adult RTRs without diabetes at baseline evaluation. HDL particle characteristics and size were measured by nuclear magnetic resonance (NMR) spectroscopy. During 5.2 (IQR, 4.1‒5.8) years of follow-up, 39 (11%) RTRs developed PTDM. In multivariable Cox regression analysis, levels of HDL cholesterol (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.40-0.94 per 1SD increase; p = 0.024) and of large HDL particles (HR 0.68, 95% CI 0.50-0.93 per log 1SD increase; p = 0.017), as well as larger HDL size (HR 0.58, 95% CI 0.36-0.93 per 1SD increase; p = 0.025) were inversely associated with PTDM development, independently of relevant covariates including, age, sex, body mass index, medication use, transplantation-specific parameters, blood pressure, triglycerides, and glucose. In conclusion, higher concentrations of HDL cholesterol and of large HDL particles and greater HDL size were associated with a lower risk of PTDM development in RTRs, independently of established risk factors for PTDM development.

Urinary Ethyl Glucuronide as Measure of Alcohol Consumption and Risk of Cardiovascular Disease: A Population-Based Cohort Study.

Background Moderate alcohol consumption has been associated with a lower risk of cardiovascular disease (CVD) and all-cause mortality compared with heavy drinkers and abstainers. To date, studies have relied on self-reported consumption, which may be prone to misclassification. Urinary ethyl glucuronide (EtG) is an alcohol metabolite and validated biomarker for recent alcohol consumption. We aimed to examine and compare the associations of self-reported alcohol consumption and EtG with CVD and all-cause mortality. Methods and Results In 5676 participants of the PREVEND (Prevention of Renal and Vascular End-Stage Disease) study cohort, EtG was measured in 24-hour urine samples and alcohol consumption questionnaires were administered. Participants were followed up for occurrence of first CVD and all-cause mortality. Cox proportional hazards regression models, adjusted for age, sex, and CVD risk factors, were fitted for self-reported consumption, divided into 5 categories: abstention, 1 to 4 units/month (reference), 2 to 7 units/week, 1 to 3 units/day, and ≥4 units/day. Similar models were fitted for EtG, analyzed as both continuous and categorical variables. Follow-up times differed for CVD (8 years; 385 CVD events) and all-cause mortality (14 years; 724 deaths). For both self-reported alcohol consumption and EtG, nonsignificant trends were found toward J-shaped associations between alcohol consumption and CVD, with higher risk in the lowest (hazard ratio for abstention versus 1-4 units/month, 1.42; 95% CI, 1.02-1.98) and highest drinking categories (hazard ratio for ≥4 units/day versus 1-4 units/month, 1.11; 95% CI, 0.68-1.84). Neither self-report nor EtG was associated with all-cause mortality. Conclusions Comparable associations with CVD events and all-cause mortality were found for self-report and EtG. This argues for the validity of self-reported alcohol consumption in epidemiologic research.

Duality of Tocopherol Isoforms and Novel Associations with Vitamins Involved in One-Carbon Metabolism: Results from an Elderly Sample of the LifeLines Cohort Study.

Whether the affinity of serum vitamin E with total lipids hampers the appropriate assessment of its association with age-related risk factors has not been investigated in epidemiological studies. We aimed to compare linear regression-derived coefficients of the association of non-indexed and total lipids-indexed vitamin E isoforms with clinical and laboratory characteristics pertaining to the lipid, metabolic syndrome, and one-carbon metabolism biological domains. We studied 1429 elderly subjects (non-vitamin supplement users, 60-75 years old, with low and high socioeconomic status) from the population-based LifeLines Cohort and Biobank Study. We found that the associations of tocopherol isoforms with lipids were inverted in total lipids-indexed analyses, which may be indicative of overcorrection. Irrespective of the methods of standardization, we consistently found positive associations of α-tocopherol with vitamins of the one-carbon metabolism pathway and inverse associations with characteristics related to glucose metabolism. The associations of γ-tocopherol were often opposite to those of α-tocopherol. These data suggest that tocopherol isoforms and one-carbon metabolism are related, with beneficial and adverse associations for α-tocopherol and γ-tocopherol, respectively. Whether tocopherol isoforms, or their interplay, truly affect the one-carbon metabolism pathway remains to be further studied.

Plasma neutrophil gelatinase-associated lipocalin at intensive care unit admission as a predictor of acute kidney injury progression.

BACKGROUND: Acute kidney injury (AKI) is a common complication in patients during intensive care unit (ICU) admission. AKI is defined as an increase in serum creatinine (SCr) and/or a reduction in urine output. SCr is a marker of renal function with several limitations, which led to the search for biomarkers for earlier AKI detection. Our aim was to study the predictive value of plasma neutrophil gelatinase-associated lipocalin (NGAL) at admission as a biomarker for AKI progression during the first 48 h of ICU admission in an unselected, heterogeneous ICU patient population. METHODS: We conducted a prospective observational study in an academic tertiary referral ICU population. We recorded AKI progression in all ICU patients during the first 48 h of ICU admission in a 6-week period. Plasma NGAL was measured at admission but levels were not reported to the attending clinicians. As possible predictors of AKI progression, pre-existing AKI risk factors were recorded. We examined the association of clinical parameters and plasma NGAL levels at ICU admission with the incidence and progression of AKI within the first 48 h of the ICU stay. RESULTS: A total of 361 patients were included. Patients without AKI progression during the first 48 h of ICU admission had median NGAL levels at admission of 115 ng/mL [interquartile range (IQR) 81-201]. Patients with AKI progression during the first 48 h of ICU admission had median NGAL levels at admission of 156 ng/mL (IQR 97-267). To predict AKI progression, a multivariant model with age, sex, diabetes mellitus, body mass index, admission type, Acute Physiology and Chronic Health Evaluation score and SCr at admission had an area under the receiver operating characteristics (ROC) curve of 0.765. Adding NGAL to this model showed a small increase in the area under the ROC curve to 0.783 (95% confidence interval 0.714-0.853). CONCLUSIONS: NGAL levels at admission were higher in patients with progression of AKI during the first 48 h of ICU admission, but adding NGAL levels at admission to a model predicting this AKI progression showed no significant additive value.