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BackgroundAlthough diabetic kidney disease is the leading cause of ESKD in the United States, identifying those patients who progress to ESKD is difficult. Efforts are under way to determine if plasma biomarkers can help identify these high-risk individuals.MethodsIn our case-cohort study of 894 Chronic Renal Insufficiency Cohort Study participants with diabetes and an eGFR of <60 ml/min per 1.73 m2 at baseline, participants were randomly selected for the subcohort; cases were those patients who developed progressive diabetic kidney disease (ESKD or 40% eGFR decline). Using a multiplex system, we assayed plasma biomarkers related to tubular injury, inflammation, and fibrosis (KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40). Weighted Cox regression models related biomarkers to progression of diabetic kidney disease, and mixed-effects models estimated biomarker relationships with rate of eGFR change.ResultsMedian follow-up was 8.7 years. Higher concentrations of KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40 were each associated with a greater risk of progression of diabetic kidney disease, even after adjustment for established clinical risk factors. After accounting for competing biomarkers, KIM-1, TNFR-2, and YKL-40 remained associated with progression of diabetic kidney disease; TNFR-2 had the highest risk (adjusted hazard ratio, 1.61; 95% CI, 1.15 to 2.26). KIM-1, TNFR-1, TNFR-2, and YKL-40 were associated with rate of eGFR decline.ConclusionsHigher plasma levels of KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40 were associated with increased risk of progression of diabetic kidney disease; TNFR-2 had the highest risk after accounting for the other biomarkers. These findings validate previous literature on TNFR-1, TNFR-2, and KIM-1 in patients with prevalent CKD and provide new insights into the influence of suPAR and YKL-40 as plasma biomarkers that require validation.

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BackgroundAfter accounting for known risk factors for CKD progression in children, clinical outcomes among children with CKD still vary substantially. Biomarkers of tubular injury (such as KIM-1), repair (such as YKL-40), or inflammation (such as MCP-1, suPAR, TNF receptor-1 [TNFR-1], and TNFR-2) may identify children with CKD at risk for GFR decline.MethodsWe investigated whether plasma KIM-1, YKL-40, MCP-1, suPAR, TNFR-1, and TNFR-2 are associated with GFR decline in children with CKD and in subgroups defined by glomerular versus nonglomerular cause of CKD. We studied participants of the prospective CKiD Cohort Study which enrolled children with an eGFR of 30–90 ml/min per 1.73 m2 and then assessed eGFR annually. Biomarkers were measured in plasma collected 5 months after study enrollment. The primary endpoint was CKD progression, defined as a composite of a 50% decline in eGFR or incident ESKD.ResultsOf the 651 children evaluated (median age 11 years; median baseline eGFR of 53 ml/min per 1.73 m2), 195 (30%) had a glomerular cause of CKD. Over a median follow-up of 5.7 years, 223 children (34%) experienced CKD progression to the composite endpoint. After multivariable adjustment, children with a plasma KIM-1, TNFR-1, or TNFR-2 concentration in the highest quartile were at significantly higher risk of CKD progression compared with children with a concentration for the respective biomarker in the lowest quartile (a 4-fold higher risk for KIM-1 and TNFR-1 and a 2-fold higher risk for TNFR-2). Plasma MCP-1, suPAR, and YKL-40 were not independently associated with progression. When stratified by glomerular versus nonglomerular etiology of CKD, effect estimates did not differ significantly.ConclusionsHigher plasma KIM-1, TNFR-1, and TNFR-2 are independently associated with CKD progression in children.

Education and literacy are key determinants of health but do not necessarily ensure health literacy (HL). The Institute of Medicine's (IOM) definition of HL is widely accepted, but there is no consensus over its constituent parts. Developing a practical measure of HL is a priority, but challenging. We aimed to derive a measure of HL in data from the Demographic and Health Surveys (DHS) Program administered by the United States Agency for International Development (USAID), which includes items representing domains of HL as defined by the IOM. We accessed data from the DHS conducted in Zambia in 2007. We applied factor analysis methods to eight survey questions that corresponded to elements of the IOM definition. We derived a single indicator and evaluated for reliability and validity. The derived dichotomous measure of HL demonstrated reliability (Cronbach's α = 0.68), good content validity, and importantly was composed of the elements described by the IOM including capacity to obtain, interpret and understand health information, and make appropriate health decisions. Only 46.5% of males and 24.5% of females had high literacy. HL varied considerably across other subgroups. This is the first study to derive a robust indicator of HL following the IOM definition in a large national sample. By applying and evaluating this method in future studies, researchers can use this approach in other DHS datasets to measure HL in additional countries, and ultimately test how HL relates to health outcomes.

Introduction: Individuals with chronic kidney disease (CKD) generally have poor participation in self-care. We hypothesized that greater kidney disease knowledge and health literacy would associate with better self-care. Methods:We enrolled 401 participants with non-dialysis-dependent CKD from one academic center in this cross-sectional study. Validated surveys were used to assess health literacy level (inadequate vs. adequate; Rapid Estimate of Adult Literacy in Medicine), perceived kidney disease knowledge (Perceived Kidney Disease Knowledge Survey [PiKS]), objective kidney disease knowledge (Kidney Disease Knowledge Survey [KiKS]), and a CKD self-care measure was constructed as the sum of self-reported self-care behaviors using the adapted Summary of Diabetes Self-Care Activities Assessment. The association between health literacy level, PiKS scores, KiKS scores, and the CKD self-care measure was assessed with multivariable adjusted linear regression models.Results: Participants had a mean age of 57 years and 17.7% had inadequate health literacy. PiKS scores were positively associated with the CKD self-care measure (b ¼ 1.05, 95% confidence interval [CI] 0.50-1.63), and a positive trend was observed for KiKS scores and the CKD self-care measure (b ¼ 0.30, 95% CI: À0.12 to 0.72). Health literacy was not associated with CKD self-care measure. Conclusion:Objective kidney disease knowledge is likely necessary, but not sufficient for self-care and may depend on the level of health literacy. Perceived kidney knowledge may offer a novel target to assess patients at risk for poor self-care, and be used in targeted educational interventions.

We sought to develop and evaluate a health literacy measure in a multi-national study and to examine demographic characteristics associated with health literacy. Data were obtained from Demographic Health Surveys conducted between 2006–15 in 14 countries in Sub-Saharan Africa. Surveys were the same in all countries but translated to local languages as appropriate. We identified eight questions that corresponded to the National Academy of Medicine (NAM) definition of health literacy. Factor analysis was used to extract one measure of health literacy. Logistic regression was employed to examine the relationship between demographic characteristics and health literacy. A total of 224 751 individuals between the ages of 15 and 49 years were included. The derived health literacy measure demonstrated good internal consistency (Cronbach’s α = 0.72) and good content validity. The prevalence of high health literacy overall was 35.77%; females 34.08% and males 39.17%; less than or equal to primary education 8.93%, some secondary education 69.40% and ≥complete secondary 84.35%. High health literacy varied across nations, from 8.51% in Niger to 63.89% in Namibia. This is the first known study to evaluate a measure of health literacy relying on the NAM definition utilizing a large sample from 14 countries in Sub-Saharan Africa. Our study derived a robust indicator of NAM-defined health literacy. This indicator could be used to examine determinants and outcomes of health literacy in additional countries.

Background Adults with chronic kidney disease (CKD) are hospitalized more frequently than those without CKD, but the magnitude of this excess morbidity and the factors associated with hospitalizations are not well known. Methods and findings Data from 3,939 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study between 2003 and 2008 at 7 clinical centers in the United States were used to estimate primary causes of hospitalizations, hospitalization rates, and baseline participant factors associated with all-cause, cardiovascular, and non-cardiovascular hospitalizations during a median follow up of 9.6 years. Multivariable-adjusted Poisson regression was used to identify factors associated with hospitalization rates, including demographics, blood pressure, estimated glomerular filtration rate (eGFR), and proteinuria. Hospitalization rates in CRIC were compared with rates in the Nationwide Inpatient Sample (NIS) from 2012. Of the 3,939 CRIC participants, 45.1% were female, and 41.9% identified as non-Hispanic black, with a mean age of 57.7 years, and the mean eGFR is 44.9 ml/min/1.73m2. CRIC participants had an unadjusted overall hospitalization rate of 35.0 per 100 person-years (PY) [95% CI: 34.3 to 35.6] and 11.1 per 100 PY [95% CI: 10.8 to 11.5] for cardiovascular-related causes. All-cause, non-cardiovascular, and cardiovascular hospitalizations were associated with older age (≥65 versus 45 to 64 years), more proteinuria (≥150 to <500 versus <150 mg/g), higher systolic blood pressure (≥140 versus 120 to <130 mmHg), diabetes (versus no diabetes), and lower eGFR (<60 versus ≥60 ml/min/1.73m2). Non-Hispanic black (versus non-Hispanic white) race/ethnicity was associated with higher risk for cardiovascular hospitalization [rate ratio (RR) 1.25, 95% CI: 1.16 to 1.35, p-value < 0.001], while risk among females was lower [RR 0.89, 95% CI: 0.83 to 0.96, p-value = 0.002]. Rates of cardiovascular hospitalizations were higher among those with ≥500 mg/g of proteinuria irrespective of eGFR. The most common causes of hospitalization were related to cardiovascular (31.8%), genitourinary (8.7%), digestive (8.3%), endocrine, nutritional or metabolic (8.3%), and respiratory (6.7%) causes. Hospitalization rates were higher in CRIC than the NIS, except for non-cardiovascular hospitalizations among individuals aged >65 years. Limitations of the study include possible misclassification by diagnostic codes, residual confounding, and potential bias from healthy volunteer effect due to its observational nature. Conclusions In this study, we observed that adults with CKD had a higher hospitalization rate than the general population that is hospitalized, and even moderate reductions in kidney function were associated with elevated rates of hospitalization. Causes of hospitalization were predominantly related to cardiovascular disease, but other causes contributed, particularly, genitourinary, digestive, and endocrine, nutritional, and metabolic illnesses. High levels of proteinuria were observed to have the largest association with hospitalizations across a wide range of kidney function levels.