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Reliable assessment of glycemia is central to the management of diabetes. The kidneys play a vital role in maintaining glucose homeostasis through glucose filtration, reabsorption, consumption, and generation. This review article highlights the role of the kidneys in glucose metabolism and discusses the benefits, pitfalls, and evidence behind the glycemic markers in patients with chronic kidney disease. We specifically highlight the role of continuous glucose monitoring as an emerging minimally invasive technique for glycemic assessment.

PurposeThe purpose of this paper is to determine the relationship between the access mode of research articles [Open Access (OA) and Toll-Access (TA)] and their subsequent citation counts in Biological and Physical Sciences in three Impact factor zones (High, Medium and Low).Design/methodology/approachThree subjects each from Biological Sciences (Biochemistry, Cell Biology and Genetics) and Physical Sciences (Astronomy, Oceanography and Optics) were selected for the study. A comprehensive list of journals (TA and OA) in select subjects of Biological and Physical Sciences was prepared by consulting Journal Citation Report’s Master Journal List (for the compilation of both Open Access and Toll Access journal list) and Directory of Open Access Journals (for the compilation of Open Access journal list). For each journal, essential details like content language, format, year of publication, access mode (Open Access or Toll Access), etc. were obtained from Ulrich’s Periodical Directory. Web of Science (WoS) was used as citations indexing tool in this study. The data set was run on the WoS to collect the citation data.FindingsThe results of the study indicate that open mode of access is not a prerequisite for higher citation boost as in the majority of the cases in this study, TA articles have garnered a greater number of citations as compared to open access articles in different Impact factor zones in Biological and Physical Sciences.Originality/valueA novel approach has been adopted to understand and compare the research impact of open access (OA) and toll access (TA) journal articles in the field of Biological and Physical Sciences at three Impact factor zone levels to reveal the citation metrics encompassing three parameters, i.e. citedness, average citation count and year wise distribution of citations in select subjects of Biological and Physical Sciences.Peer reviewThe peer review history for this article is available at: https://publons.com/publon/[DOI]/10.1108/OIR-01-2021-0029

Patients with kidney failure suffer high mortality, and we currently lack markers for risk stratification for these patients. We carried out a quality control study of a modified aptamer assay (SomaScan v.4.0) that measures ~ 5000 proteins, in preparation for a larger study using this platform in cohorts with kidney failure. Forty participants from the Cardiac, Endothelial Function and Arterial Stiffness in End-Stage Renal Disease (CERES study) were selected to analyze technical and short-term biological variability, orthogonal correlations and differential protein expression in plasma from patients who died during 2.5 year follow-up. Long-term (one year) variability was studied in 421 participants in the Chronic Renal Insufficiency Cohort. We evaluated 4849 aptamers (4607 unique proteins) using data formats including raw data and data formatted using Adaptive Normalization by Maximum Likelihood (ANML), an algorithm developed for SomaScan data in individuals with normal kidney function. In ANML format, median[IQR] intra-assay coefficient of variation (CV) was 2.38%[1.76, 3.40] and inter-assay CV was 7.38%[4.61, 13.12]. Short-term within-subject CV was 5.76% [3.35, 9.72]; long-term CV was 8.71%[5.91, 13.37]. Spearman correlations between aptamer and traditional assays for PTH, NT-proBNP, FGF-23 and CRP were all > 0.7. Fold-change (FC) in protein levels among non-survivors, significant after Bonferroni correction, included SVEP1 (FC[95% CI] 2.14 [1.62, 2.82]), keratocan (1.74 [1.40, 2.15]) and LanC-like protein 1 (0.56 [0.45, 0.70]). Compared to raw aptamer data, technical and short-term biological variability in paired samples was lower in ANML-formatted data. ANML formatting had minimal impact on orthogonal correlations with traditional assays or the associations of proteins with the phenotype of mortality. SomaScan had excellent technical variability and low within-subject short-term variability. ANML formatting could facilitate comparison of biomarker results with other studies that utilize this format. We expect SomaScan to provide novel and reproducible information in patients with kidney failure on dialysis.

This study aimed to investigate the association of nonalcoholic fatty liver disease (NAFLD) and its severity with the decline in kidney function in patients with chronic kidney disease (CKD). We conducted a cohort study of 1,525 CKD patients who underwent repeated health check-up examinations from January 2003 through December 2013. NAFLD was diagnosed by ultrasonography and its severity was assessed by the NAFLD fibrosis score. At baseline, the prevalence of NAFLD was 40.9%, and the mean estimated glomerular filtration rate (eGFR) was 59.1 ml/min/1.73 m 2 . The average follow-up was 6.5 years. The age- and sex-adjusted decline in eGFR was greater in patients with NAFLD (−0.79% per year, 95% CI −1.31%, −0.27%) compared to those without it (0.30%, 95% CI −0.14%, 0.76%; p = 0.002). In multivariable adjusted models, the average difference in annual percent change in decline in eGFR comparing patients with NAFLD to those without NAFLD was −1.06% (−1.73%, −0.38%; p = 0.002). The decline in eGFR associated with NAFLD was greater in patients with higher NAFLD fibrosis score, in those with proteinuria or with low eGFR at baseline ( <45 ml/min/1.73 m 2 ), and in those who were smokers and hypertensive. Therefore, NAFLD is independently associated with CKD progression.

Impaired physical function contributes to falls, fractures, and mortality among patients undergoing dialysis. Using a metabolomic approach, we identified metabolite alterations and effect size-based composite scores for constructs of impaired gait speed and grip strength. 108 participants incident to dialysis had targeted plasma metabolomics via liquid chromatography-mass spectrometry and physical function assessed (i.e., 4 m walk, handgrip strength). Physical function measures were categorized as above/ below median, with grip utilizing sex-based medians. To develop composite scores, metabolites were identified via Wilcoxon uncorrected p  < 0.05 and effect size > 0.40. Receiver operating characteristic analyses tested whether scores differentiated between above/below function groups. Participants were 54% male, 77% Black and 53 ± 14 y with dialysis vintage of 101 ± 50 days. Median (IQR) grip strength was 35.5 (11.1) kg (males) and 20 (8.4) kg (females); median gait speed was 0.82 (0.34) m/s. Of 246 measured metabolites, composite scores were composed of 22 and 12 metabolites for grip strength and gait speed, respectively. Area under the curve for metabolite composite was 0.88 (gait) and 0.911 (grip). Composite scores of physical function performed better than clinical parameters alone in patients on dialysis. These results provide potential pathways for interventions and needed validation in an independent cohort.

Background Apparent treatment-resistant hypertension (aTRH) is a common condition associated with risk of cardiovascular events. However, the risk of cardiovascular mortality associated with aTRH in the US population is unknown. We aimed to assess the risk of cardiovascular disease (CVD) mortality associated with aTRH in the US population. Methods We analyzed data from 6357 adult hypertensive participants of the National Health and Nutrition Examination Survey (1988–1994 and 1999–2010) linked to the National Death Index. Based on presence of uncontrolled hypertension [blood pressure (BP) ≥140/90 mmHg] and the number of antihypertensives prescribed, we classified participants into the following groups: non-aTRH (BP < 140/90 mmHg and ≤ 3 antihypertensives); controlled aTRH (BP < 140/90 mmHg and ≥ 4 antihypertensives); and uncontrolled aTRH (BP ≥140/90 mmHg and ≥ 3 antihypertensives). Results Of the 6357 participants, 1522 had aTRH, representing a US prevalence of 7.6 million. Of the participants with aTRH, 432 had controlled aTRH and 1090 had uncontrolled aTRH. During follow-up (median 6 years), there were 550 CVD deaths. The cumulative incidence of CVD mortality was significantly higher in the aTRH group compared with non-aTRH group (log-rank p  < 0.001). In fully adjusted models, aTRH was associated with a 47% higher risk of CVD mortality compared with the non-aTRH group [1.47 (1.1–1.96)]. Similar increase in risk of CVD mortality was noted across aTRH subgroups compared with the non-aTRH group: controlled aTRH [1.66 (1.03–2.68)] and uncontrolled aTRH [1.43 (1.05–1.94)]. Among non-aTRH subgroups, those on 3 antihypertensive medications had a 35% increased risk of CVD mortality than those on < 3 medications [1.35 (0.98–1.86)]. Conclusions aTRH is a common condition, affecting approximately 7.6 million Americans. Regardless of BP control, people with aTRH remain at a higher risk of cardiovascular outcomes. The risk of cardiovascular disease mortality remains high among those with controlled BP on 3 medications (non-aTRH) or ≥ 4 medications (controlled aTRH), groups not generally considered at high risk. Future risk reduction interventions should consider focusing on these high-risk groups.

Numerous substances accumulate in the body in uremia but those contributing to cardiovascular morbidity and mortality in dialysis patients are still undefined. We examined the association of baseline free levels of four organic solutes that are secreted in the native kidney - p-cresol sulfate, indoxyl sulfate, hippurate and phenylacetylglutamine - with outcomes in hemodialysis patients. We measured these solutes in stored specimens from 394 participants of a US national prospective cohort study of incident dialysis patients. We examined the relation of each solute and a combined solute index to cardiovascular mortality and morbidity (first cardiovascular event) using Cox proportional hazards regression adjusted for demographics, comorbidities, clinical factors and laboratory tests including Kt/VUREA. Mean age of the patients was 57 years, 65% were white and 55% were male. In fully adjusted models, a higher p-cresol sulfate level was associated with a greater risk (HR per SD increase; 95% CI) of cardiovascular mortality (1.62; 1.17-2.25; p=0.004) and first cardiovascular event (1.60; 1.23-2.08; p<0.001). A higher phenylacetylglutamine level was associated with a greater risk of first cardiovascular event (1.37; 1.18-1.58; p<0.001). Patients in the highest quintile of the combined solute index had a 96% greater risk of cardiovascular mortality (1.96; 1.05-3.68; p=0.04) and 62% greater risk of first cardiovascular event (1.62; 1.12-2.35; p=0.01) compared with patients in the lowest quintile. Results were robust in sensitivity analyses. Free levels of uremic solutes that are secreted by the native kidney are associated with a higher risk of cardiovascular morbidity and mortality in incident hemodialysis patients.

Assays for serum total glycated proteins (fructosamine) and the more specific glycated albumin may be useful indicators of hyperglycemia in dialysis patients, either as substitutes or adjuncts to standard markers such as hemoglobin A1c, as they are not affected by erythrocyte turnover. However, their relationship with long-term outcomes in dialysis patients is not well described. We measured fructosamine and glycated albumin in baseline samples from 503 incident hemodialysis participants of a national prospective cohort study, with enrollment from 1995-1998 and median follow-up of 3.5 years. Outcomes were all-cause and cardiovascular disease (CVD) mortality and morbidity (first CVD event and first sepsis hospitalization) analyzed using Cox regression adjusted for demographic and clinical characteristics, and comorbidities. Mean age was 58 years, 64% were white, 54% were male, and 57% had diabetes. There were 354 deaths (159 from CVD), 302 CVD events, and 118 sepsis hospitalizations over follow-up. Both fructosamine and glycated albumin were associated with all-cause mortality; adjusted HR per doubling of the biomarker was 1.96 (95% CI 1.38-2.79) for fructosamine and 1.40 (1.09-1.80) for glycated albumin. Both markers were also associated with CVD mortality [fructosamine 2.13 (1.28-3.54); glycated albumin 1.55 (1.09-2.21)]. Higher values of both markers were associated with trends toward a higher risk of hospitalization with sepsis [fructosamine 1.75 (1.01-3.02); glycated albumin 1.39 (0.94-2.06)]. Serum fructosamine and glycated albumin are risk factors for mortality and morbidity in hemodialysis patients.

More than 50% of patients with kidney failure undergoing maintenance hemodialysis die within 5 years, a fate unexplained by traditional risk factors. To identify biological risk factors, we analyze 6287 circulating proteins and mortality in 893 participants undergoing hemodialysis in the Chronic Renal Insufficiency Cohort (CRIC) and Predictors of Arrhythmic and Cardiovascular Risk in End-Stage Renal Disease (PACE) studies. Proteins are measured shortly after (incident period) and one year after (prevalent period) dialysis initiation. In CRIC prevalent period, Sushi von Willebrand factor type A EGF and pentraxin domain-containing protein 1(SVEP1), R-spondin 4, tetranectin and 24 other proteins attain Bonferroni significance (p < 7 × 10 -6 ). At false discovery rate<0.05, 184 proteins are significant in CRIC; 123/184 remain significant after adjustment for covariates including those linked to inflammation. Pathways related to insulin-like growth factor are prominent. In the pooled CRIC + PACE cohort, prevalent time period, AUC(95%CI) for a 3-protein model of 5-year mortality is 0.826 (0.742, 0.896), compared to 0.629 (0.528, 0.722) for a Cohort Clinical model (p < 0.001). Adding the 3 proteins (SVEP1, R-spondin 4 and tetranectin) to the Cohort Clinical model significantly improves the AUC (p < 0.001). These biomarkers should be validated in future studies and their roles as potential disease mediators elucidated. Patients with kidney failure undergoing maintenance hemodialysis have poor long-term survival. Here the authors use affinity-based proteomics to identify circulating risk factors for mortality in patients with kidney failure on hemodialysis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.