Plasma Uromodulin Correlates With Kidney Function and Identifies Early Stages in Chronic Kidney Disease Patients

Uromodulin, released from tubular cells of the ascending limb into the blood, may be associated with kidney function. This work studies the relevance of plasma uromodulin as a biomarker for kidney function in an observational cohort of chronic kidney disease (CKD) patients and subjects without CKD (CKD stage 0). It should be further evaluated if uromodulin allows the identification of early CKD stages. Plasma uromodulin, serumcreatinine, cystatin C, blood-urea-nitrogen (BUN) concentrations, and estimated glomerular filtration rate (eGFR CKD-EPIcrea-cystatin) were assessed in 426 individuals of whom 71 were CKD stage 0 and 355 had CKD. Besides descriptive statistics, univariate correlations between uromodulin and biomarkers/eGFR were calculated using Pearson-correlation coefficient. Multiple linear regression modeling was applied to establish the association between uromodulin and eGFR adjusted for demographic parameters and pharmacologic treatment. Receiver-operating-characteristic (ROC) analysis adjusted for demographic parameters was performed to test if uromodulin allows differentiation of subjects with CKD stage 0 and CKD stage I. Mean uromodulin plasma levels were 85.7 +/- 60.5 ng/mL for all CKD stages combined. Uromodulin was correlated with all biomarkers/eGFR in univariate analysis (eGFR: r = 0.80, creatinine: r = +/- 0.76, BUN: r = +/- 0.72, and cystatin C: r = +/- 0.79). Multiple linear regression modeling showed significant association between uromodulin and eGFR (coefficient estimate beta = 0.696, 95% confidence interval [CI] 0.603-0.719, P<0.001). In ROC analysis uromodulin was the only parameter that significantly improved a model containing demographic parameters to differentiate between CKD 0 degrees and I degrees (area under the curve [AUC] 0.831, 95% CI 0.746-0.915, P = 0.008) compared to creatinine, cystatin C, BUN, and eGFR (AUC for creatinine: 0.722, P = 0.056, cystatin C: 0.668, P = 0.418, BUN: 0.653, P = 0.811, and eGFR: 0.634, P = 0.823). Plasma uromodulin serves as a robust biomarker for kidney function and uniquely allows the identification of early stages of CKD. As a marker of tubular secretion it might represent remaining nephron mass and therefore intrinsic "kidney function'' rather than just glomerular filtration, the latter only being of limited value to represent kidney function as a whole. It therefore gives substantial information on the renal situation in addition to glomerular filtration and potentially solves the problem of creatinine-blind range of CKD, in which kidney impairment often remains undetected

Plasma Uromodulin Correlates With Kidney Function and Identifies Early Stages in Chronic Kidney Disease Patients

Uromodulin, released from tubular cells of the ascending limb into the blood, may be associated with kidney function. This work studies the relevance of plasma uromodulin as a biomarker for kidney function in an observational cohort of chronic kidney disease (CKD) patients and subjects without CKD (CKD stage 0). It should be further evaluated if uromodulin allows the identification of early CKD stages. Plasma uromodulin, serumcreatinine, cystatin C, blood-urea-nitrogen (BUN) concentrations, and estimated glomerular filtration rate (eGFR CKD-EPIcrea-cystatin) were assessed in 426 individuals of whom 71 were CKD stage 0 and 355 had CKD. Besides descriptive statistics, univariate correlations between uromodulin and biomarkers/eGFR were calculated using Pearson-correlation coefficient. Multiple linear regression modeling was applied to establish the association between uromodulin and eGFR adjusted for demographic parameters and pharmacologic treatment. Receiver-operating-characteristic (ROC) analysis adjusted for demographic parameters was performed to test if uromodulin allows differentiation of subjects with CKD stage 0 and CKD stage I. Mean uromodulin plasma levels were 85.7 +/- 60.5 ng/mL for all CKD stages combined. Uromodulin was correlated with all biomarkers/eGFR in univariate analysis (eGFR: r = 0.80, creatinine: r = +/- 0.76, BUN: r = +/- 0.72, and cystatin C: r = +/- 0.79). Multiple linear regression modeling showed significant association between uromodulin and eGFR (coefficient estimate beta = 0.696, 95% confidence interval [CI] 0.603-0.719, P<0.001). In ROC analysis uromodulin was the only parameter that significantly improved a model containing demographic parameters to differentiate between CKD 0 degrees and I degrees (area under the curve [AUC] 0.831, 95% CI 0.746-0.915, P = 0.008) compared to creatinine, cystatin C, BUN, and eGFR (AUC for creatinine: 0.722, P = 0.056, cystatin C: 0.668, P = 0.418, BUN: 0.653, P = 0.811, and eGFR: 0.634, P = 0.823). Plasma uromodulin serves as a robust biomarker for kidney function and uniquely allows the identification of early stages of CKD. As a marker of tubular secretion it might represent remaining nephron mass and therefore intrinsic "kidney function'' rather than just glomerular filtration, the latter only being of limited value to represent kidney function as a whole. It therefore gives substantial information on the renal situation in addition to glomerular filtration and potentially solves the problem of creatinine-blind range of CKD, in which kidney impairment often remains undetected

Associations Between C-Reactive Protein, Insulin Sensitivity, and Resting Metabolic Rate in Adults: A Mediator Analysis

Objective: Long-term positive energy balance promotes the development of obesity, a main risk factor for type 2 diabetes mellitus (T2DM). While an association between increased resting metabolic rate (RMR) and insulin sensitivity (IS) was shown previously, the underlying mechanisms remain unclear. Aim of the mediator analysis was to investigate the role of inflammation within the association between RMR and IS.Methods: Anthropometric, clinical, and lifestyle data were collected according to standard operating procedures. RMR was measured using indirect calorimetry. Homeostasis model assessment for insulin resistance (HOMA-IR) was used as an IS parameter and C-reactive protein (CRP) was measured to represent the inflammatory status. Statistical analyses were performed using SPSS.Results: The analysis included 782 adults (517 females) with a mean age of 32.4 ± 12.0 years and a mean body mass index (BMI) of 24.6 ± 5.2 kg/m2. Regression analysis indicated a significant evidence for associations between RMR and HOMA-IR (ß = 39.3 ± 7.3 kcal/d; p ≤ 0.001) and CRP and HOMA-IR (ß = 0.5 ± 0.1; p ≤ 0.001) after adjustment for fat-free mass, sex, age, and study site. Results of the mediator analysis did not support the hypothesis that CRP is a mediator for the association between RMR and HOMA-IR. These results did not change after participant stratification according to sex or BMI.Conclusion: A significant evidence for an association between RMR and IS was shown in a large cohort. However, the inflammatory status, determined via CRP levels, was not a mediator within this association

One-Year Weight Loss with a Telephone-Based Lifestyle Program

Objective: Telephone-based weight loss programs are offered as an alternative to face-to-face obesity treatments, but data on the effectiveness regarding weight loss are limited. Therefore, we evaluated a telephone-based lifestyle program in a real-world setting. Methods: The telephone-based intervention consists of regular phone calls providing individualized lifestyle recommendations, and delivery of printed materials. Anthropometric and metabolic data are collected by general practitioners or are self-reported. Results: Baseline data were available from 398 participants (61% men; weight 103.12 ± 14.21 kg; BMI 33.38 ± 2.83 kg/m2) and 1-year data from 258 (65%) participants. In the completers, mean weight change was -4.25 ± 5.18 kg (p Conclusions: The telephone-based lifestyle program results in a moderate weight loss after 12 months, which may be comparable to face-to-face interventions. Telephone-based weight loss support is independent of time and location and represents a tool which is also accepted by men

Sustained low efficiency dialysis should not be interrupted for performing transpulmonary thermodilution measurements

Abstract Background Treatment of multiple organ failure frequently requires enhanced hemodynamic monitoring. When renal replacement is indicated, it remains unclear whether transpulmonary thermodilution (TPTD) measurements are influenced by renal replacement therapy (RRT) and whether RRT should be paused for TPTD measurements. Our aim was therefore to investigate the effect of pausing RRT on TPTD results in two dialysis catheter locations. Materials and methods In total, 62 TPTD measurements in 24 patients (APACHE: 32 ± 7 [mean ± standard deviation (SD)]) were performed using the PiCCO™ system (Pulsion, Germany). Patients were treated with sustained low efficiency dialysis (SLED; Genius™ system, Fresenius, Germany) as RRT. Measurements were taken during ongoing hemodialysis (HD, HDO), during paused HD (HDP) and immediately after termination of HD and blood restitution (HDT). Dialysis catheters were placed either in the superior vena cava (SVC, 19 times) or in the inferior vena cava (IVC, 5 times). Statistical analysis was performed to assess the effects of the measurement setting, SLED (blood flow rate) and the catheter location, on cardiac index (CI), global end-diastolic volume index (GEDVI) and extravascular lung water index (EVLWI) as measured by TPTD. Multilevel models were used for the analysis due to the triplicate measurements and due to 12 out of 19 SVC and 2 out of 5 IVC patients having more than one TPTD measured. Results CI and GEDVI were significantly higher at time point HDP compared to both HDO and HDT. In contrast, values for EVLWI were lower at HDP when compared to HDO and HDT. These findings were independent of the site of dialysis catheter insertion and blood flow rate. Conclusions PiCCO™ measurements assessed at paused SLED significantly deviate from ongoing and terminated SLED. Therefore, the dialysis system should not be paused for measurements. TPTD measurements in patients with PiCCO monitoring seem sufficiently reliable during ongoing SLED as well as after its termination. An effect of dialysis catheter location (SVC vs IVC) and blood flow rate on PiCCO™ measurements could not be shown

Associations between lifestyle interventions during pregnancy and childhood weight and growth: a systematic review and meta-analysis

BACKGROUND: Maternal health and lifestyle during pregnancy may be critical for the onset and progression of childhood obesity. Prenatal lifestyle interventions have been shown to positively affect maternal behaviors, gestational weight gain, and anthropometric outcomes in infants at birth. The influence of such interventions on child weight or growth beyond birth is unknown. We therefore examined the association between lifestyle interventions during pregnancy and anthropometric outcomes during childhood. METHODS: A systematic literature search was conducted in three electronic databases, two clinical trial registers and further sources, without language or publication status restrictions. Additionally, 110 study authors were contacted to obtain unpublished data. Randomized controlled trials comparing any antenatal lifestyle or behavioral intervention to standard prenatal care, in women of any body mass index (BMI), with offspring anthropometric data at 1 month of age or older, were considered. Two reviewers independently extracted data and assessed the risk of bias using the Cochrane Collaboration’s updated tool. Data on weight, length, and BMI, and corresponding z-scores, were stratified into six age ranges and weighted mean differences (WMD) with 95% confidence intervals (CI) were calculated in univariate and multivariate random-effects meta-analytical models. RESULTS: Twenty trials comprising 11,385 women were included in this systematic review, of which 19 were combined in meta-analyses. Overall, lifestyle interventions during pregnancy were not associated with differences in weight, length, BMI, or corresponding z-scores, in children aged 1 month to 7 years (e.g. weight in 5 to 6 month old children, WMD: 0.02 kg; 95% CI: − 0.05 to 0.10 kg, I² = 38%; 13 studies, 6667 participants). Findings remained consistent when studies were stratified by maternal baseline BMI or other risk factors, and intervention content and duration. Based on the GRADE criteria, the strength of the body of evidence was considered moderate. CONCLUSION: Prenatal lifestyle interventions were not shown to influence childhood weight or growth. Nevertheless, women should be encouraged to pursue a healthy lifestyle during pregnancy. Further efforts to establish early prevention strategies for childhood obesity are urgently needed. Thus, large, high-quality studies with pre-planned, long-term follow-ups are warranted. TRIAL REGISTRATION: PROSPERO CRD42018118678

Human papillomavirus vaccine guideline adherence among Arizona\u27s Medicaid beneficiaries

© 2020 Elsevier Ltd Cancers caused by human papillomavirus (HPV) can be prevented with the timely uptake and completion of the HPV vaccine series. Series completion is associated with increased vaccine effectiveness and longevity of protection. Medicaid beneficiaries are among populations with higher HPV vaccine uptake; however, little research describes factors that influence their HPV vaccine series completion. This study reports on a secondary data analysis of Arizona Medicaid data (Arizona Health Care Cost Containment System) from years 2008–2016. We summarized patient data using descriptive statistics and explored relationships between demographic variables and HPV vaccine administration information using bivariate logistic regression. Results of this analysis showed that females were more likely to complete the series as compared to males, and the age group that had the greatest odd of vaccine completion were 13–17-year-olds, the catch-up vaccine population. White Medicaid beneficiaries were most likely to adhere to HPV vaccine guidelines, followed by Hispanic beneficiaries. Patients receiving care in urban settings were more likely to complete the HPV vaccine series than people receiving care in rural areas of the state. Although statistically insignificant, people living with HIV were less likely to complete the 3-dose series. Future work should focus on ensuring that HPV vaccine age-eligible Medicaid, including people living with HIV, adhere to HPV vaccine guidelines. Expanding programs such as Vaccines for Children and scope of practice for dental professionals to offer the vaccine may provide additional options for Medicaid beneficiaries to vaccinate

Impact of Dietary Macronutrient Intake during Early and Late Gestation on Offspring Body Composition at Birth, 1, 3, and 5 Years of Age

Dietary intake during pregnancy as a possible modifiable risk factor for childhood obesity is poorly explored. In a prospective observational study, two multivariable regression models were therefore used to associate maternal diet at 15 and 32 weeks&rsquo; gestation with offsprings&rsquo; body composition and fat distribution at birth, 1, 3, and 5 years. Mean energy intake was 2157 &plusmn; 375 kcal (n = 186) in early and 2208 &plusmn; 460 kcal (n = 167) in late gestation. The partition model showed mostly no significant associations between maternal diet in early pregnancy and offspring body composition. In late pregnancy, higher fat intake was negatively associated with clinical outcomes at birth, 1, and 5 years. Protein intake was negatively associated with BMI z score (zBMI) at 3 and 5 years. A 10 g increase in fiber was associated with an increase of 3.50 mm2 abdominal subcutaneous fat at 1, 172.49 g fat mass at 3, and 0.23 zBMI at 5 years. Results were largely comparable in the substitution model. An incremental increase in fat and protein at the expense of carbohydrates in late but not early pregnancy may be associated with lower fat mass up to 5 years. Findings require confirmation by additional prospective studies