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BackgroundUromodulin modulates the sodium-potassium-two-chloride transporter in the thick ascending limb of the loop of Henle, and its overexpression in murine models leads to salt-induced hypertension. We hypothesized that individuals with higher baseline levels of urine uromodulin would have a greater increase in systolic blood pressure (SBP) for the same increase in sodium compared with those with lower uromodulin levels.MethodsWe used data from 157 subjects randomized to the control diet of the Dietary Approaches to Stop Hypertension (DASH)-Sodium trial who were assigned to 30 days of low (1,500 mg/d), medium (2,400 mg/d), and high salt (3,300 mg/d) diets in random order. Blood pressure was measured prerandomization and then weekly during each feeding period. We evaluated the association of prerandomization urine uromodulin with change in SBP between diets, as measured at the end of each feeding period, using multivariable linear regression.ResultsBaseline urine uromodulin stratified by tertiles was ≤17.64, 17.65-31.97, and ≥31.98 µg/ml. Across the tertiles, there were no significant differences in SBP at baseline, nor was there a differential effect of sodium diet on SBP across tertiles (low to high, P = 0.81). After adjusting for age, sex, body mass index, and race, uromodulin levels were not significantly associated with SBP change from low to high sodium diet (P = 0.42).ConclusionsIn a randomized trial of different levels of salt intake, higher urine uromodulin levels were not associated with a greater increase in blood pressure in response to high salt intake.

Apparent treatment-resistant hypertension (ATRH) is highly prevalent and associated with cardiovascular disease risk in patients with chronic kidney disease. We analyzed the association of inflammatory biomarkers with ATRH and its complications in patients with chronic kidney disease. ATRH was defined as blood pressure ≥140/90 mm Hg while taking ≥3 antihypertensive medications or blood pressure

Few investigations have evaluated the incremental usefulness of tubular injury biomarkers for improved prediction of chronic kidney disease (CKD) progression. As such, we measured urinary kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, N-acetyl-ß-D-glucosaminidase and liver fatty acid binding protein under highly standardized conditions among 2466 enrollees of the prospective Chronic Renal Insufficiency Cohort Study. During 9433 person-years of follow-up, there were 581 cases of CKD progression defined as incident end-stage renal disease or halving of the estimated glomerular filtration rate. Levels of the urine injury biomarkers, normalized for urine creatinine, were strongly associated with CKD progression in unadjusted Cox proportional hazard models with hazard ratios in the range of 7 to 15 comparing the highest with the lowest quintiles. However, after controlling for the serum creatinine-based estimated glomerular filtration rate and urinary albumin/creatinine ratio, none of the normalized biomarkers was independently associated with CKD progression. None of the biomarkers improved on the high (0.89) C-statistic for the base clinical model. Thus, among patients with CKD, risk prediction with a clinical model that includes the serum creatinine-based estimated glomerular filtration rate and the urinary albumin/creatinine ratio is not improved on with the addition of renal tubular injury biomarkers.

ObjectiveExplore the association between following a Dietary Approaches to Stop Hypertension (DASH)-accordant diet and kidney end points among urban adults.DesignProspective cohort study.SettingHealthy Aging in Neighborhoods of Diversity across the Life Span study.SubjectsA total of 1,534 urban dwelling participants of the Healthy Aging in Neighborhoods of Diversity across the Life Span study with a baseline estimated glomerular filtration rate (eGFR) ≥60 mL/minute/1.73 m2.InterventionDASH diet accordance determined via a score based on nine target nutrients.Main outcome measureRapid kidney function decline (eGFR decline >3 mL/minute/1.73 m2 per year), incident chronic kidney disease (CKD) (follow-up eGFR 25%.ResultsParticipants' mean age was 48 years, and 59% were African-American. Median DASH score was 1.5 (range, 0-8). Over a median of 5 years, 13.4% experienced rapid eGFR decline, including 15.2% among participants not following a DASH-accordant diet (score ≤1) and 12.0% with higher accordance (score >1) (P = .08). Outcomes varied by hypertension status. In multinomial logistic regression models, following adjustment for sociodemographic and clinical factors, including total energy intake, low DASH diet accordance was associated with rapid eGFR decline among participants with hypertension (risk ratio, 1.68; 95% confidence interval: 1.17-2.42) but not among those without hypertension (risk ratio, 0.83; 95% confidence interval: 0.56-1.24; P interaction .001). There was no statistically significant association between DASH diet accordance and incident CKD or eGFR decline >25%. Results were similar when DASH diet accordance was analyzed in tertiles.ConclusionsAmong urban adults, low accordance to a DASH-type diet was not associated with incident CKD, but was associated with higher risk of rapid eGFR decline among those with hypertension, yet not among those without hypertension. Further study of dietary patterns as a potential target for improving kidney outcomes among high-risk populations is warranted.

BackgroundPoverty is associated with chronic kidney disease (CKD) in the United States and worldwide. Poor dietary habits may contribute to this disparity.Study designCross-sectional study.Setting and participantsA total of 2,058 community-dwelling adults aged 30 to 64 years residing in Baltimore City, Maryland.PredictorsAdherence to the Dietary Approaches to Stop Hypertension (DASH) diet. DASH scoring based on 9 target nutrients (total fat, saturated fat, protein, fiber, cholesterol, calcium, magnesium, sodium, and potassium); adherence defined as score ≥4.5 of maximum possible score of 9. Poverty (self-reported household income

BackgroundChronic kidney disease is common and is associated with increased cardiovascular disease risk. Currently, markers of renal tubular injury are not used routinely to describe kidney health and little is known about the risk of cardiovascular events and death associated with these biomarkers independent of glomerular filtration-based markers (such as serum creatinine or albuminuria).Study designCohort study, CRIC (Chronic Renal Insufficiency Cohort) Study.Setting & participants3,386 participants with estimated glomerular filtration rate of 20 to 70mL/min/1.73m(2) enrolled from June 2003 through August 2008.PredictorUrine neutrophil gelatinase-associated lipocalin (NGAL) concentration.OutcomesAdjudicated heart failure event, ischemic atherosclerotic event (myocardial infarction, ischemic stroke, or peripheral artery disease), and death through March 2011.MeasurementsUrine NGAL measured at baseline with a 2-step assay using chemiluminescent microparticle immunoassay technology on an ARCHITECT i2000SR (Abbott Laboratories).ResultsThere were 428 heart failure events (during 16,383 person-years of follow-up), 361 ischemic atherosclerotic events (during 16,584 person-years of follow-up), and 522 deaths (during 18,214 person-years of follow-up). In Cox regression models adjusted for estimated glomerular filtration rate, albuminuria, demographics, traditional cardiovascular disease risk factors, and cardiac medications, higher urine NGAL levels remained associated independently with ischemic atherosclerotic events (adjusted HR for the highest [>49.5ng/mL] vs lowest [≤6.9ng/mL] quintile, 1.83 [95% CI, 1.20-2.81]; HR per 0.1-unit increase in log urine NGAL, 1.012 [95% CI, 1.001-1.023]), but not heart failure events or deaths.LimitationsUrine NGAL was measured only once.ConclusionsAmong patients with chronic kidney disease, urine levels of NGAL, a marker of renal tubular injury, were associated independently with future ischemic atherosclerotic events, but not with heart failure events or deaths.

ObjectiveDiabetes and hypertension, common conditions in antiretroviral-treated HIV-infected individuals, are associated with glomerular hyperfiltration, which precedes the onset of proteinuria and accelerated kidney function decline. In the Multicenter AIDS Cohort Study, we examined the extent to which hyperfiltration is present and associated with metabolic, cardiovascular, HIV and treatment risk factors among HIV-infected men.DesignCross-sectional cohort using direct measurement of glomerular filtration rate by iohexol plasma clearance for 367 HIV-infected men and 241 HIV-uninfected men who were free of chronic kidney disease.MethodsHyperfiltration was defined as glomerular filtration rate above 140-1 ml/min per 1.73 m per year over age 40. Multivariate logistic regression was used to estimate the odds ratios (ORs) of prevalent hyperfiltration for metabolic, cardiovascular, HIV and cumulative antiretroviral exposure factors.ResultsAmong individuals without chronic kidney disease, the prevalence of hyperfiltration was higher for HIV-infected participants (25%) compared to uninfected participants (17%; P = 0.01). After adjustment, HIV infection remained associated with hyperfiltration [OR 1.70, 95% confidence interval (CI) 1.11-2.61] and modified the association between diabetes and hyperfiltration, such that the association among HIV-uninfected men (OR 2.56, 95% CI 1.33-5.54) was not observed among HIV-infected men (OR 1.19, 95% CI 0.69-2.05). These associations were independent of known risk factors for hyperfiltration. Indicators of hyperglycemia and hypertension were also associated with hyperfiltration as was cumulative zidovudine exposure.ConclusionHyperfiltration, a potential modifiable predictor of kidney disease progression, is significantly higher among antiretroviral-treated HIV-infected men. Furthermore, HIV-infection nullifies the association of diabetes and hyperfiltration present in HIV-uninfected men.

Abstract Background Racial disparities in blood pressure control have been well documented in the United States. Research suggests that many factors contribute to this disparity, including barriers to care at patient, clinician, healthcare system, and community levels. To date, few interventions aimed at reducing hypertension disparities have addressed factors at all of these levels. This paper describes the design of Project ReD CHiP (Reducing Disparities and Controlling Hypertension in Primary Care), a multi-level system quality improvement project. By intervening on multiple levels, this project aims to reduce disparities in blood pressure control and improve guideline concordant hypertension care. Methods Using a pragmatic trial design, we are implementing three complementary multi-level interventions designed to improve blood pressure measurement, provide patient care management services and offer expanded provider education resources in six primary care clinics in Baltimore, Maryland. We are staggering the introduction of the interventions and will use Statistical Process Control (SPC) charting to determine if there are changes in outcomes at each clinic after implementation of each intervention. The main hypothesis is that each intervention will have an additive effect on improvements in guideline concordant care and reductions in hypertension disparities, but the combination of all three interventions will result in the greatest impact, followed by blood pressure measurement with care management support, blood pressure measurement with provider education, and blood pressure measurement only. This study also examines how organizational functioning and cultural competence affect the success of the interventions. Discussion As a quality improvement project, Project ReD CHiP employs a novel study design that specifically targets multi-level factors known to contribute to hypertension disparities. To facilitate its implementation and improve its sustainability, we have incorporated stakeholder input and tailored components of the interventions to meet the specific needs of the involved clinics and communities. Results from this study will provide knowledge about how integrated multi-level interventions can improve hypertension care and reduce disparities. Trial Registration ClinicalTrials.gov NCT01566864

BackgroundAlbuminuria is an important risk factor for progressive chronic kidney disease (CKD) and is more prevalent in black than white adults. We sought to determine the association between low income and albuminuria and whether this association differs for blacks and whites.Study designCross-sectional study.Setting & participants9,144 black and 13,684 white US adults 45 years and older in the population-based Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study.PredictorsSelf-reported annual household income category (≥$75,000, $35,000-$74,999, $20,000-$34,999, and 300 mg/g) urinary albumin-creatinine ratio (ACR). Multinomial logistic regression used to examine the race-stratified association between categories of income and albuminuria (normal, high, or very high ACR).ResultsOverall, geometric mean ACR was 10.2 mg/g and was higher for blacks (11.8 mg/g) than whites (9.3 mg/g), P

Background Hepcidin is a key mediator of the anemia of chronic kidney disease (CKD). There is emerging evidence that 25-hydroxyvitamin D (25D) regulates hepcidin production. Methods A randomized controlled trial of daily vitamin D supplementation for 12 weeks was performed with the aim to test the effects of 4000 versus 400 IU of cholecalciferol on serum hepcidin levels in children with non-dialysis CKD recruited at a tertiary care children's hospital. Hepcidin was quantified using a validated competitive enzyme-linked immunosorbent assay. 25D levels were measured using the chemiluminescence Liaison 25(OH)D assay system. Co-variables included hemoglobin, C-reactive protein, ferritin, and serum calcium and phosphorus for safety monitoring. Results A total of 34 subjects were randomized to either the intervention or control group, of whom 26.5% were female and 23.5% were African American. The mean age of the study cohort was 10.9 [standard deviation (SD) 5.8] years, the mean baseline glomerular filtration rate was 60 (SD 17.6) ml/min/1.73 m.sup.2, and mean baseline 25D level was 29.7 (SD 11.5) ng/ml. At baseline, 50% of subjects were 25D deficient. There were no significant differences in baseline characteristics between the intervention and control groups. Treatment with 4000 IU cholecalciferol was not associated with significant change in hepcidin level at 4 or 12 weeks, and multivariable generalized estimating equation regression demonstrated no significant difference in change in hepcidin over the treatment period in either arm. The median C-reactive protein level decreased significantly at 12 weeks in the intervention group. Conclusions These results do not suggest that daily nutritional vitamin D supplementation modifies serum hepcidin levels in children with CKD. Further study will be required to determine whether supplementation may be effective in children with more advanced CKD or those on dialysis., Author(s): Meredith A. Atkinson [sup.1] , Stephen P. Juraschek [sup.2] [sup.3] , Michael S. Bertenthal [sup.1] , Barbara Detrick [sup.4] , Susan L. Furth [sup.5] , Edgar R. III Miller [...]