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BackgroundIt is not well established whether a virtual multidisciplinary care program for persons with advanced chronic kidney disease (CKD) can improve their knowledge about their disease, increase their interest in home dialysis therapies, and result in more planned outpatient (versus inpatient) dialysis starts. ObjectiveWe aimed to evaluate the feasibility and preliminary associations of program participation with disease knowledge, home dialysis modality preference, and outpatient dialysis initiation among persons with advanced CKD in a community-based nephrology practice. MethodsIn a matched prospective cohort, we enrolled adults aged 18 to 85 years with at least two estimated glomerular filtration rates (eGFRs) of less than 30 mL/min/1.73 m2 into the Cricket Health program and compared them with controls receiving care at the same clinic, matched on age, gender, eGFR, and presence of heart failure and diabetes. The intervention included online education materials, a virtual multidisciplinary team (nurse, pharmacist, social worker, dietician), and patient mentors. Prespecified follow-up time was nine months with extended follow-up to allow adequate time to determine the dialysis start setting. CKD knowledge and dialysis modality choice were evaluated in a pre-post survey among intervention participants. ResultsThirty-seven participants were matched to 61 controls by age (mean 67.2, SD 10.4 versus mean 68.8, SD 9.5), prevalence of diabetes (54%, 20/37 versus 57%, 35/61), congestive heart failure (22%, 8/37 versus 25%, 15/61), and baseline eGFR (mean 19, SD 6 versus mean 21, SD 5 mL/min/1.73 m2), respectively. At nine-month follow-up, five patients in each group started dialysis (P=.62). Among program participants, 80% (4/5) started dialysis as an outpatient compared with 20% (1/5) of controls (OR 6.28, 95% CI 0.69-57.22). In extended follow-up (median 15.7, range 11.7 to 18.1 months), 19 of 98 patients started dialysis; 80% (8/10) of the intervention group patients started dialysis in the outpatient setting versus 22% (2/9) of control patients (hazard ratio 6.89, 95% CI 1.46-32.66). Compared to before participation, patients who completed the program had higher disease knowledge levels (mean 52%, SD 29% versus mean 94%, SD 14% of questions correct on knowledge-based survey, P

BACKGROUND: Mortality is high within the first few months of starting chronic dialysis. Pre-ESKD trajectory of kidney function has been shown to be predictive of early death after dialysis initiation. We aim to better understand how two key aspects of pre-dialysis kidney function-an abrupt transition pattern and an episode of dialysis-requiring AKI (AKI-D) leading directly to ESKD-are associated with early mortality after dialysis initiation. METHODS: We extracted national data from U.S. Veterans Health Administration cross-linked with the United States Renal Data System (USRDS) to identify patients who initiated hemodialysis during 2009-2013. We defined abrupt transition as having a mean outpatient eGFR ≥ 30 ml/min/1.73m2 within 1 year prior to ESKD. AKI-D was identified using inpatient serum creatinine measurements (serum Cr increase by at least 50% from baseline) along with billing codes for inpatient receipt of dialysis for AKI within 30 days prior to the ESKD start date. We used multivariable proportional hazards models to examine the association between patterns of kidney function prior to ESKD and all-cause mortality within 90 days after ESKD. RESULTS: Twenty-two thousand eight hundred fifteen patients were identified in the final analytic cohort of Veterans who initiated hemodialysis and entered the USRDS. We defined five patterns of kidney function decline. Most (68%) patients (N = 15,484) did not have abrupt transition and did not suffer an episode of AKI-D prior to ESKD (reference group). The remaining groups had abrupt transition, AKI-D, or both. Patients who had an abrupt transition with (N = 503) or without (N = 3611) AKI-D had the highest risk of early mortality after ESKD onset after adjustment for demographics and comorbidities (adjusted HR 2.10, 95% CI 1.66-2.65 for abrupt transition with AKI-D; adjusted HR 2.10, 95% CI 1.90-2.33 for abrupt transition without AKI-D). In contrast, patients who experienced AKI-D without an abrupt transition pattern (N =  2141 had only a modestly higher risk of early death (adjusted HR 1.19, 95% CI 1.01-1.40). CONCLUSIONS: An abrupt decline in kidney function within 1 year prior to ESKD occurred in nearly 1 in 5 incident hemodialysis patients (18%) in this national cohort of Veterans and was strongly associated with higher early mortality after ESKD onset.

BACKGROUND: Urine biomarkers of kidney tubule health may distinguish aspects of kidney damage that cannot be captured by current glomerular measures. Associations of clinical risk factors with specific kidney tubule biomarkers have not been evaluated in detail. METHODS: We performed a cross-sectional study in the Systolic Blood Pressure Intervention Trial among 2,436 participants with a baseline estimated glomerular filtration rate (eGFR)

OBJECTIVE: To assess the prevalence and correlates of prescription of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and/or glucagon-like peptide 1 receptor agonists (GLP1-RA) in individuals with type 2 diabetes mellitus (T2DM) with and without chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS: This was a cross-sectional analyses of SGLT2i and GLP1-RA prescriptions from 1 January 2019 to 31 December 2020 in the Veterans Health Administration System. The likelihood of prescriptions was examined by the presence or absence of CKD and by predicted risks of atherosclerotic cardiovascular disease (ASCVD) and end-stage kidney disease (ESKD). RESULTS: Of 1,197,880 adults with T2DM, SGLT2i and GLP1-RA were prescribed to 11% and 8% of patients overall, and to 12% and 10% of those with concomitant CKD, respectively. In adjusted models, patients with severe albuminuria were less likely to be prescribed SGLT2i or GLP1-RA versus nonalbuminuric patients with CKD, with odds ratios (ORs) of 0.91 (95% CI 0.89, 0.93) and 0.97 (0.94, 1.00), respectively. Patients with a 10-year ASCVD risk >20% (vs. 5%, compared with

BACKGROUND: Inadequate treatment of high blood pressure (BP) can lead to preventable adverse events in nursing home residents, while excessive treatment can lead to associated harms. METHODS: Data were extracted from the VA electronic health record and Bar Code Medication Administration system on 40,079 long-term care residents aged ≥65 years from October 2006 through September 2018 (FY2007-2018). Hypertension prevalence at admission was identified by ICD code(s) in the year prior, and antihypertensive medication use was defined as administration ≥50% of days. BP measures were averaged over 2-year epochs. RESULTS: The age-standardized prevalence of hypertension diagnosis at admission increased from 75.2% in FY2007-2008 to 85.1% in FY2017-2018 (p-value for trend 140/90 mmHg. Future research is needed to better understand the benefits and harms of BP control in nursing home residents.

BackgroundAging is accompanied by an overall dysregulation of many dynamic physiologic processes including those related to blood pressure (BP). While year-to-year BP variability is associated with cardiovascular events and mortality, no studies have examined this trend with more frequent BP assessments. Our study objective is to take the next step to examine week-to-week BP dynamics-pattern, variability, and complexity-before death.MethodsUsing a retrospective study design, we assessed BP dynamics in the 6 months before death in long-term nursing home residents between 1 October 2006 and 30 September 2017. Variability was characterized using SD and mean squared error after adjusting for diurnal variations. Complexity (i.e., amount of novel information in a trend) was examined using Shannon's entropy (bits). Generalized linear models were used to examine factors associated with overall BP variability.ResultsWe identified 17,953 nursing home residents (98.0% male, 82.5% White, mean age 80.2 years, and mean BP 125.7/68.6 mm Hg). Despite a slight trend of decreasing systolic week-to-week BP over time (delta = 7.2 mm Hg), week-to-week complexity did not change in the 6 months before death (delta = 0.02 bits). Average weekly BP variability was stable until the last 3-4 weeks of life, at which point variability increased by 30% for both systolic and diastolic BP. Factors associated with BP variability include average weekly systolic/diastolic BP, days in the nursing home, days in the hospital, and changes to antihypertensive medications.ConclusionsWeek-to-week BP variability increases substantially in the last month of life, but complexity does not change. Changes in care patterns may drive the increase in BP variability as one approaches death.

BackgroundThere are major gaps in the implementation of guideline-concordant care for persons with chronic kidney disease (CKD). The CKD Cascade of Care (C3) initiative seeks to improve CKD care by improving detection and treatment of CKD in primary care.MethodsC3 is a multi-modal initiative deployed in three major academic medical centers within the Department of Veterans Affairs (VA) Health Care System: San Francisco VA, San Diego VA, and Houston VA. The main objective of the first phase of C3 described in this protocol is to establish the infrastructure for universal CKD detection among primary care patients at high-risk for CKD with a triple-marker screen comprising cystatin C, creatinine, and albuminuria. Across the three sites, a comprehensive educational intervention and the integration of primary care-based clinical champions will be employed with the goal of improving CKD detection and treatment. The San Francisco VA will also implement a practice-facilitation intervention leveraging telehealth and health informatics tools and capabilities for enhanced CKD detection. Parallel formative evaluation across the three sites will assess the feasibility and acceptability of integrating cystatin C as part of routine CKD detection in primary care practice. The effectiveness of the interventions will be assessed using a pre-post observational design for change in the proportion of patients tested annually for CKD. Secondary outcomes will assess change in the initiation of cardio-kidney protective therapies and in nephrology referrals of high-risk patients.DiscussionThe first phase of C3 is a multi-facility multi-modal initiative that aims to improve CKD care by implementing a triple-marker screen for enhanced CKD detection in primary care.

BackgroundCertain classes of antihypertensive medication may have different associations with cognitive impairment.ObjectiveTo examine the association between prevalent use of antihypertensive medications that stimulate (thiazides, dihydropyridine calcium channel blockers, angiotensin type I receptor blockers) versus inhibit (angiotensin-converting enzyme inhibitors, beta-blockers, non-dihydropyridine calcium channel blockers) type 2 and 4 angiotensin II receptors on cognitive impairment among older adults residing in Veterans Affairs (VA) nursing homes for long-term care.MethodsRetrospective cohort study. Long-term care residents aged 65 + years admitted to a VA nursing home from 2012 to 2019 using blood pressure medication and without cognitive impairment at admission. Main exposure was prevalent use of angiotensin II receptor type 2 and 4-'stimulating' (N = 589), 'inhibiting' (N = 3,219), or 'mixed' (N = 1,715) antihypertensive medication regimens at admission. Primary outcome was any cognitive impairment (Cognitive Function Scale).ResultsOver an average of 5.4 months of follow-up, prevalent use of regimens containing exclusively 'stimulating' antihypertensives was associated with a lower risk of any incident cognitive impairment as compared to prevalent use of regimens containing exclusively 'inhibiting' antihypertensives (HR 0.83, 95% CI 0.74-0.93). Results for the comparison between 'mixed' versus 'inhibiting' regimens were in the same direction but not statistically significant (HR 0.96, 95% CI 0.88-1.06).ConclusionFor residents without cognitive impairment at baseline, prevalent users of regimens containing exclusively antihypertensives that stimulate type 2 and 4 angiotensin II receptors had lower rates of cognitive impairment as compared to prevalent users of regimens containing exclusively antihypertensives that inhibit these receptors. Residual confounding cannot be ruled out.

ObjectivesTo evaluate the incidence of deprescribing of antihypertensive medication among older adults residing in Veterans Affairs (VA) nursing homes for long-term care and rates of deprescribing after potentially triggering events.DesignRetrospective cohort study.Setting and participantsLong-term care residents aged 65 years and older admitted to a VA nursing home from 2006 to 2019 and using blood pressure medication at admission.MethodsData were extracted from the VA electronic health record, and Centers for Medicare & Medicaid Services Minimum Data Set and Bar Code Medication Administration. Deprescribing was defined on a rolling basis as a reduction in the number or dose of antihypertensive medications, sustained for ≥2 weeks. We examined potentially triggering events for deprescribing, including low blood pressure (

BACKGROUND/OBJECTIVES: Non-steroidal anti-inflammatory drugs (NSAIDs) can cause kidney injury, especially in older adults. However, previously reported associations between NSAID use and kidney health outcomes are inconsistent and limited by reliance on serum creatinine-based GFR estimates. This analysis investigated the association of NSAID use with kidney damage in older adults using multiple kidney health measures. DESIGN: Cross-sectional and longitudinal analyses. SETTING: Multicenter, community-based cohort. PARTICIPANTS: Two thousand nine hundred and ninty nine older adults in the Health ABC Study. A subcohort (n = 500) was randomly selected for additional biomarker measurements. EXPOSURE: Prescription and over-the-counter NSAID use ascertained by self-report. MEASUREMENTS: Baseline estimated glomerular filtration rate (eGFR) by cystatin C (cysC), urine albumin-to-creatinine ratio (ACR), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) were measured in 2,999 participants; alpha-1 microglobulin (α1m), neutrophil gelatinase-associated lipocalin (NGAL), propeptide type III procollagen (PIIINP), and uromodulin (UMOD) were measured in 500 participants. GFR was estimated three times over 10 years and expressed as percent change per year. RESULTS: Participants had a mean age of 74 years, 51% were female, and 41% African-American. No eGFR differences were detected between NSAID users (n = 655) and non-users (n = 2,344) at baseline (72 ml/min/1.73 m2 in both groups). Compared to non-users, NSAID users had lower adjusted odds of having ACR greater than 30 mg/g (0.67; 95% confidence interval (CI) = 0.51-0.89) and lower mean urine IL-18 concentration at baseline (-11%; 95% CI = -4% to -18%), but similar mean KIM-1 (5%; 95% CI = -5% to 14%). No significant differences in baseline concentrations of the remaining urine biomarkers were detected. NSAID users and non-users did not differ significantly in the rate of eGFR decline (-2.2% vs -2.3% per year). CONCLUSION: Self-reported NSAID use was not associated with kidney dysfunction or injury based on multiple measures, raising the possibility of NSAID use without kidney harm in ambulatory older adults. More research is needed to define safe patterns of NSAID consumption.

Rationale & objectiveMost adults with chronic kidney disease (CKD) in the United States are cared for by primary care providers (PCPs). We evaluated the feasibility and preliminary effectiveness of an electronic clinical decision support system (eCDSS) within the electronic health record with or without pharmacist follow-up to improve the management of CKD in primary care.Study designPragmatic cluster-randomized trial.Setting & participants524 adults with confirmed creatinine-based estimated glomerular filtration rates of 30 to 59mL/min/1.73m2 cared for by 80 PCPs at the University of California San Francisco. Electronic health record data were used for patient identification, intervention deployment, and outcomes ascertainment.InterventionsEach PCP's eligible patients were randomly assigned as a group into 1 of 3 treatment arms: (1) usual care; (2) eCDSS: testing of creatinine, cystatin C, and urinary albumin-creatinine ratio with individually tailored guidance for PCPs on blood pressure, potassium, and proteinuria management, cardiovascular risk reduction, and patient education; or (3) eCDSS plus pharmacist counseling (eCDSS-PLUS).OutcomesThe primary clinical outcome was change in blood pressure over 12 months. Secondary outcomes were PCP awareness of CKD and use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and statin therapy.ResultsAll 80 eligible PCPs participated. Mean patient age was 70 years, 47% were nonwhite, and mean estimated glomerular filtration rate was 56±0.6mL/min/1.73m2. Among patients receiving eCDSS with or without pharmacist counseling (n=336), 178 (53%) completed laboratory measurements and 138 (41%) had laboratory measurements followed by a PCP visit with eCDSS deployment. eCDSS was opened by the PCP for 102 (74%) patients, with at least 1 suggested order signed for 83 of these 102 (81%). Changes in systolic blood pressure were-2.1±1.5mm Hg with usual care, -2.8±1.8mm Hg with eCDSS, and -1.1±1.1 with eCDSS-PLUS (P=0.7). PCP awareness of CKD was 16% with usual care, 26% with eCDSS, and 32% for eCDSS-PLUS (P=0.09). In as-treated analyses, PCP awareness of CKD was significantly greater with eCDSS and eCDSS-PLUS (73% and 69%) versus usual care (47%; P=0.002).LimitationsRecruitment of smaller than intended sample size and limited uptake of the testing component of the intervention.ConclusionsAlthough we were unable to demonstrate the effectiveness of eCDSS to lower blood pressure and uptake of the eCDSS was limited by low testing rates, eCDSS use was high when laboratory measurements were available and was associated with higher PCP awareness of CKD.FundingGrants from government (National Institutes of Health) and not-for-profit (American Heart Association) entities.Trial registrationRegistered at ClinicalTrials.gov with study number NCT02925962.

Background APOL1 high-risk genotypes are associated with increased risk for hypertension-attributed kidney disease among Black adults in the United States. Biopsy studies show differences in kidney vasculature by APOL1 status; less is known about the variants' associations with systemic vascular and endothelial function. Whether APOL1 risk variants are associated with blood pressure (BP) is also uncertain. Methods and Results Using linear regression, we examined cross-sectional associations of APOL1 risk genotypes (high=2 risk alleles, low=0 or 1 risk allele) with subclinical measures of vascular function (small arterial elasticity, n=1586; large arterial elasticity, n=1586; ascending aortic distensibility, n=985) and endothelial function (flow-mediated dilation, n=777). Using linear mixed-effects models, we studied longitudinal associations of APOL1 risk genotypes with BP (n=1619), adjusting for age, sex, and African ancestry. Among 1619 (12% APOL1 high-risk) Black participants in MESA (Multi-Ethnic Study of Atherosclerosis), mean age was 62 years old, 58% had hypertension, and mean systolic BP was 131 mm Hg at baseline. At examination 1 (2000-2002), there was no significant difference in small arterial elasticity, large arterial elasticity, ascending aortic distensibility, or flow-mediated dilation in participants with APOL1 high- versus low-risk genotypes (P>0.05 for all). Over a mean follow-up of 7.8 years, relative annual changes in systolic and diastolic BP and pulse pressure did not differ significantly by APOL1 risk status (between-group differences of -0.20, -0.14, and -0.25, respectively; P>0.05 for all). Conclusions Among Black participants in MESA, APOL1 high-risk genotypes were not associated with subclinical vascular and endothelial function or BP trajectories. The relationship of APOL1 with kidney disease may be intrinsic to the kidney rather than through peripheral effects on systemic vasculature or BP.

ObjectiveTo determine whether cerebral small vessel disease or disability modify the effect of SBP treatment on cognitive and vascular outcomes in older patients with recent lacunar stroke.MethodsParticipants aged at least 65 years of the Secondary Prevention of Small Subcortical Strokes Trial were randomized to a higher (130-149 mmHg) or lower (

Heterogeneous exposure associations (HEAs) can be defined as differences in the association of an exposure with an outcome among subgroups that differ by a set of characteristics. In this article, we intend to foster discussion of HEAs in the epidemiologic literature and present a variant of the random forest algorithm that can be used to identify HEAs. We demonstrate the use of this algorithm in the setting of the association between systolic blood pressure and death in older adults. The training set included pooled data from the baseline examination of the Cardiovascular Health Study (1989-1993), the Health, Aging, and Body Composition Study (1997-1998), and the Sacramento Area Latino Study on Aging (1998-1999). The test set included data from the National Health and Nutrition Examination Survey (1999-2002). The hazard ratios ranged from 1.25 (95% confidence interval: 1.13, 1.37) per 10-mm Hg increase in systolic blood pressure among men aged ≤67 years with diastolic blood pressure greater than 80 mm Hg to 1.00 (95% confidence interval: 0.96, 1.03) among women with creatinine concentration ≤0.7 mg/dL and a history of hypertension. HEAs have the potential to improve our understanding of disease mechanisms in diverse populations and guide the design of randomized controlled trials to control exposures in heterogeneous populations.

BackgroundThe majority of people with chronic kidney disease (CKD) are unaware of their kidney disease. Assessing the clinical significance of increasing CKD awareness has critical public health and healthcare delivery implications. Whether CKD awareness among persons with CKD is associated with longitudinal health behaviors, disease management, and health outcomes is unknown.MethodsWe analyzed data from participants with CKD in the REasons for Geographic And Racial Differences in Stroke study, a national, longitudinal, population-based cohort. Our predictor was participant CKD awareness. Outcomes were (1) health behaviors (smoking avoidance, exercise, and nonsteroidal anti-inflammatory drug use); (2) CKD management indicators (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, statin use, systolic blood pressure, fasting blood glucose, and body mass index); (3) change in estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR); and (4) health outcomes (incident end-stage kidney disease [ESKD], coronary heart disease [CHD], stroke, and death). Logistic and linear regressions were used to examine the association of baseline CKD awareness with outcomes of interest, adjusted for CKD stage and participant demographic and clinical factors.ResultsOf 6,529 participants with baseline CKD, 285 (4.4%) were aware of their CKD. Among the 3,586 participants who survived until follow-up (median 9.5 years), baseline awareness was not associated with subsequent odds of health behaviors, CKD management indicators, or changes in eGFR and UACR in adjusted analyses. Baseline CKD awareness was associated with increased risk of ESKD (adjusted hazard ratio [aHR] 1.44; 95% CI 1.08-1.92) and death (aHR 1.18; 95% CI 1.00-1.39), but not with subsequent CHD or stroke, in adjusted models.ConclusionsIndividuals aware of their CKD were more likely to experience ESKD and death, suggesting that CKD awareness reflects disease severity. Most persons with CKD, including those that are high-risk, remain unaware of their CKD. There was no evidence of associations between baseline CKD awareness and longitudinal health behaviors, CKD management indicators, or eGFR decline and albuminuria.

BackgroundAlthough microvascular dysfunction is known to result from diabetes, it might also lead to diabetes. Lower values of C2, a derivative of the radial artery pressure waveform, indicate microvascular dysfunction and predict hypertension and cardiovascular disease (CVD). We studied the association of C2 with incident diabetes in subjects free of overt CVD.MethodsAmong multi-ethnic participants (n = 5214), aged 45-84 years with no diabetes, C2 was derived from the radial artery pressure waveform. Incident diabetes (N = 651) was diagnosed as new fasting glucose ≥ 126 mg/dL or antidiabetic medicine over ~ 10 years. The relative incidence density (RID) for incident diabetes per standard deviation (SD) of C2 was studied during ~ 10 years follow-up using four levels of adjustment.ResultsMean C2 at baseline was 4.58 ± 2.85 mL/mmHg × 100. The RID for incident diabetes per SD of C2 was 0.90 (95% CI 0.82-0.99, P = 0.03). After adjustment for demographics plus body size, the corresponding RID was 0.81 (95% CI 0.73-0.89, P

BackgroundThe diagnosis of chronic kidney disease (CKD) is based on laboratory results easily extracted from electronic health records; therefore, CKD identification and management is an ideal area for targeted electronic decision support efforts. Early CKD management frequently occurs in primary care settings where primary care providers (PCPs) may not implement all the best practices to prevent CKD-related complications. Few previous studies have employed randomized trials to assess a CKD electronic clinical decision support system (eCDSS) that provided recommendations to PCPs tailored to each patient based on laboratory results.ObjectiveThe aim of this study was to report the trial design and implementation experience of a CKD eCDSS in primary care.MethodsThis was a 3-arm pragmatic cluster-randomized trial at an academic general internal medicine practice. Eligible patients had 2 previous estimated-glomerular-filtration-rates by serum creatinine (eGFRCr)

Introduction: Grafts with alcohol-associated liver disease (ALD) subjected to prolonged cold ischaemia from donors after brain death (DBD) are typically unsuitable for transplantation. Here, we investigated the role of growth hormone (GH) in livers with ALD from DBDs and its relationship with vascular endothelial growth factor A (VEGFA) and VEGFB. Methods: Livers from rats fed ethanol for 6 weeks and with brain death (BD) were cold stored for 24 h and subjected to ex vivo reperfusion. Hepatic damage and proliferative and inflammatory parameters were analysed after BD, before graft retrieval, and after reperfusion. Survival was monitored using an in vivo transplantation model. Results: In DBDs, the administration of GH, which increased the levels in the intestine but not in the liver, induced the generation of both VEGFA and VEGFB in the intestine and protected against hepatic damage caused by BD before retrieving liver grafts from donors. However, VEGFA was the only factor that protected against damage after cold ischemia and reperfusion, which also increased the survival of the recipients. Discussion: In conclusion, the signalling pathway and beneficial properties of the GH-VEGFA/VEGFB pathway, in which the intestine-liver axis plays a key role, were disrupted when grafts with ALD from DBDs were retrieved from donors and subjected to cold ischemia and reperfusion. [ABSTRACT FROM AUTHOR]

Background We aimed to determine whether cerebral white matter hyperintensities ( WMHs ) can distinguish stroke survivors susceptible to rapid kidney function decline from intensive blood pressure ( BP ) lowering. Methods and Results The SPS3 (Secondary Prevention of Small Subcortical Strokes) trial randomized participants with recent lacunar stroke to systolic BP targets of 130 to 149 and

Rationale & objectiveChronic kidney disease (CKD) is complicated by abnormalities that reflect disruption in filtration, tubular, and endocrine functions of the kidney. Our aim was to explore the relationship of specific laboratory result abnormalities and hypertension with the estimated glomerular filtration rate (eGFR) and albuminuria CKD staging framework.Study designCross-sectional individual participant-level analyses in a global consortium.Setting & study populations17 CKD and 38 general population and high-risk cohorts.Selection criteria for studiesCohorts in the CKD Prognosis Consortium with data for eGFR and albuminuria, as well as a measurement of hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, or calcium, or hypertension.Data extractionData were obtained and analyzed between July 2015 and January 2018.Analytical approachWe modeled the association of eGFR and albuminuria with hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, and calcium values using linear regression and with hypertension and categorical definitions of each abnormality using logistic regression. Results were pooled using random-effects meta-analyses.ResultsThe CKD cohorts (n=254,666 participants) were 27% women and 10% black, with a mean age of 69 (SD, 12) years. The general population/high-risk cohorts (n=1,758,334) were 50% women and 2% black, with a mean age of 50 (16) years. There was a strong graded association between lower eGFR and all laboratory result abnormalities (ORs ranging from 3.27 [95% CI, 2.68-3.97] to 8.91 [95% CI, 7.22-10.99] comparing eGFRs of 15 to 29 with eGFRs of 45 to 59mL/min/1.73m2), whereas albuminuria had equivocal or weak associations with abnormalities (ORs ranging from 0.77 [95% CI, 0.60-0.99] to 1.92 [95% CI, 1.65-2.24] comparing urinary albumin-creatinine ratio > 300 vs < 30mg/g).LimitationsVariations in study era, health care delivery system, typical diet, and laboratory assays.ConclusionsLower eGFR was strongly associated with higher odds of multiple laboratory result abnormalities. Knowledge of risk associations might help guide management in the heterogeneous group of patients with CKD.

Background We aimed to determine whether cerebral white matter hyperintensities ( WMHs ) can distinguish stroke survivors susceptible to rapid kidney function decline from intensive blood pressure ( BP ) lowering. Methods and Results The SPS3 (Secondary Prevention of Small Subcortical Strokes) trial randomized participants with recent lacunar stroke to systolic BP targets of 130 to 149 and

BACKGROUND: Electronic health record (EHR) data is increasingly used to identify patients with chronic kidney disease (CKD). EHR queries used to capture CKD status, identify comorbid conditions, measure awareness by providers, and track adherence to guideline-concordant processes of care have not been validated. METHODS: We extracted EHR data for primary-care patients with two eGFRcreat 15-59 mL/min/1.73 m^2 at least 90 days apart. Two nephrologists manually reviewed a random sample of 50 charts to determine CKD status, associated comorbidities, and physician awareness of CKD. We also assessed the documentation of a CKD diagnosis with guideline-driven care. RESULTS: Complete data were available on 1767 patients with query-defined CKD of whom 822 (47%) had a CKD diagnosis in their chart. Manual chart review confirmed the CKD diagnosis in 34 or 50 (68%) patients. Agreement between the reviewers and the EHR diagnoses on the presence of comorbidities was good (κ > 0.70, p

ObjectiveThe objective of the study is to evaluate the association of intergenerational educational attainment with cardiovascular disease (CVD) risk factors among US Latinos.MethodsWe used cross-sectional data from the Niños Lifestyle and Diabetes Study, an offspring cohort of middle-aged Mexican-Americans whose parents participated in the Sacramento Latino Study on Aging. We collected educational attainment, demographic and health behaviours and measured systolic blood pressure (SBP), fasting glucose and waist circumference. We evaluated the association of parental, offspring and a combined parent-offspring education variable with each CVD risk factor using multivariable regression.ResultsHigher parental education was associated only with smaller offspring waist circumference. In contrast, higher offspring education was associated with lower SBP, fasting glucose and smaller waist circumference. Adjustment for parental health behaviours modestly attenuated these offspring associations, whereas adjustment for offspring health behaviours and income attenuated the associations of offspring education with offspring SBP and fasting glucose but not smaller waist circumference, even among offspring with low parental education.ConclusionsHigher offspring education is associated with lower levels of CVD risk factors in adulthood, despite intergenerational exposure to low parental education.

IntroductionUrinary neutrophil gelatinase-associated lipocalin (uNGAL) and urinary kidney injury molecule-1 (uKIM-1) are established markers of subclinical acute kidney injury. In persons with reduced estimated glomerular filtration rate (eGFR) and albuminuria who are at high risk for end-stage renal disease (ESRD) and death, the associations of these urinary markers with incident ESRD or death is an area of active investigation.MethodsAmong 1472 black and white participants from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study with eGFR ≤60 ml/min per 1.73 m2 (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] cystatin, 2012) and albumin-to-creatinine ratio (ACR) ≥30 mg/g, we evaluated the associations of baseline uNGAL and uKIM-1 with progression to ESRD and all-cause death. Cox models were sequentially adjusted for urinary creatinine, traditional risk factors, C-reactive protein, ACR, and eGFR.ResultsThere were 257 ESRD events and 819 deaths over a median follow-up of 5.7 and 6.5 years, respectively. In demographic adjusted models, higher levels of uNGAL were associated with increased risk of ESRD and death, but these associations were attenuated in fully adjusted models including baseline eGFR for both ESRD (hazard ratio [HR] = 1.06 per doubling, 95% confidence interval [CI] 0.98-1.14) and death (HR = 1.04, 95% CI = 1.00-1.08). Higher levels of uKIM-1 were associated with increased risk of ESRD and death in demographic-adjusted models, and although attenuated in fully adjusted models, remained statistically significant for both ESRD (HR = 1.24 per doubling, 95% CI = 1.08-1.42) and death (HR = 1.10, 95% CI =1.03-1.19).ConclusionIn this cohort of high-risk patients with baseline eGFR ≤60 ml/min per 1.73 m2 and albuminuria, renal tubular injury is associated with higher mortality and progression to ESRD. Further studies are necessary to investigate the mechanism underlying this increased risk.

BackgroundMany studies have focused on the association between a single blood pressure (BP) measurement and risk for adverse outcomes. However, the association of BP trajectories during young adulthood with subsequent decline in kidney function has not been well defined.Study designObservational cohort study.Setting & participants3,429 participants in the Coronary Artery Risk Development in Young Adulthood (CARDIA) Study enrolled between the ages of 18 and 30 years.PredictorsBP slope during the first 10 years of participation in CARDIA, derived from linear mixed models incorporating all repeated BP measures.OutcomeDecline in estimated glomerular filtration rate (eGFR) during the interval between years 10 and 20 of CARDIA participation using cystatin C measured at years 10, 15, and 20.ResultsMean age of CARDIA participants at year 0 was 25.1 years, 56% were women, and 53% were white. Every 10-mmHg higher level of systolic (SBP) and diastolic BP (DBP) in year 10 was associated with change in eGFR of -0.09 (95% CI, -0.13 to -0.06) and -0.07 (95% CI, -0.12 to -0.03) mL/min/1.73m2 per year, respectively. Every 10-mmHg increase in SBP slope between years 0 and 10 was associated with a subsequent -0.52 (95% CI, -1.02 to -0.03) mL/min/1.73m2 per year change in kidney function after adjustment for comorbid conditions and SBP at year 10. Similarly, every 10-mmHg increase in DBP slope between years 0 and 10 was associated with a subsequent change in kidney function of -0.65 (95% CI, -1.23 to -0.07) mL/min/1.73m2 per year, after adjustment for comorbid conditions and DBP in year 10.LimitationsObservational design.ConclusionsDuring young adulthood, increasing SBP and DBP are associated with a higher rate of subsequent kidney function decline, independent of BP measured at the beginning of eGFR assessment.

BackgroundPrevious studies in HIV-infected individuals have demonstrated serum albumin to be strongly associated with kidney function decline, independent of urine albumin and inflammatory markers. Lower serum albumin concentrations may be an under-appreciated risk factor for kidney function decline in elders.MethodsWe performed a cohort analysis in the Health Aging and Body Composition Study, a cohort of well-functioning, bi-racial, community-dwelling elders between the age of 70 and 79 years. We examined the associations of serum albumin concentration with longitudinal kidney function decline by estimated glomerular filtration rate (eGFR). Outcomes included linear eGFR decline, rapid kidney function decline defined as >30% decrease in eGFR, defined as a final eGFR 60 mL/min/1.73 m2 at baseline. Cystatin C-based eGFR was calculated at baseline, Year 3 and Year 10.ResultsMean age was 74 years, and mean eGFR was 73 mL/min/1.73 m2 at baseline. The mean rate of eGFR change was 1.81 mL/min/1.73 m2 per year. After multivariate adjustment, lower serum albumin concentrations were strongly and independently associated with kidney function decline (-0.11 mL/min/1.73 m2 per year for each standard deviation decrease serum albumin; -0.01 to - 0.20) with no attenuation after adjustment for urine albumin and inflammatory markers (-0.12, -0.03 to - 0.22). When divided into quartiles, serum albumin levels ≤3.80 g/dL were associated with increased odds of rapid kidney function decline (odds ratio 1.59; 1.12-2.26) and increased risk of incident chronic kidney disease (incident rate ratio 1.29; 1.03-1.62) relative to levels >4.21g/dL. Urine albumin to creatinine ratio (ACR) was also significantly and independently associated with kidney function decline (-0.08 mL/min/1.73 m2 per year for urine ACR >30 mg/g; -0.82 to - 0.13).ConclusionsLower serum albumin levels are strongly and independently associated with kidney function decline in elders, independent of clinical risk factors, urine albumin and measured inflammatory markers.

BackgroundWhile changes in blood pressure (BP) are independently associated with cardiovascular events, less is known about the association between changes in BP and subsequent changes in renal function in adults with an estimated glomerular filtration rate (eGFR) of >60 ml/min/1.73 m2.MethodsThe present study included 3,920 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) study who had ≥2 BP measurements during the first 5 years of MESA and had eGFR measurements at both year 5 and 10. Change in BP was estimated as the annualized slope of BP between year 0 and 5 based on linear mixed models (mean number of measurements = 4.0). Participants were then grouped into 1 of 3 categories based on the distribution of systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) change (top 20%, middle 21-79%, bottom 20%). We calculated eGFR from cystatin C (ml/min/1.73 m2), estimated annual change in eGFR (ml/min/1.73 m2/year), and defined rapid kidney function decline as a >30% decrease in eGFR from year 5 to 10. We used multivariable logistic regression adjusting for year 0 demographic and clinical characteristics, including eGFR and BP, to determine associations of BP change with rapid kidney function decline.ResultsMedian age was 59 [interquartile range (IQR): 52, 67] and median eGFR at year 0 was 95.5 (IQR: 81.7, 105.9) ml/min/1.73 m2. Median SBP at year 0 was 111, 121, and 147 mm Hg for increasing, stable, and decreasing SBP change, respectively. Increasing SBP and widening PP change were each associated with higher odds of rapid kidney function decline compared with stable SBP and PP groups, respectively [odds ratio, OR 1.7 (95% confidence interval, CI 1.3, 2.4) for SBP; OR 1.4 (95% CI 1.1, 1.9) for PP]. Decreasing SBP was associated with rapid kidney function decline after adjusting for all covariates except for year 0 BP [OR 1.4 (95% CI 1.0, 1.8)], but this association was no longer statistically significant after adjustment for year 0 BP. There were no significant associations between DBP change and rapid decline in the fully adjusted models. Similar findings were seen with annual change in eGFR.ConclusionsIncreasing SBP and widening PP over time were associated with greater risk for accelerated kidney function decline even at BP levels below established hypertension thresholds.

PurposeWe applied cluster analysis to identify discrete patterns of concomitant responses of systolic (SBP), diastolic (DBP) and pulse pressure (PP) during intensive BP lowering; and to evaluate their clinical relevance and association with risk of mortality, major vascular events (MVEs), and stroke.Material and methodsWe used an unsupervised cluster procedure to identify distinct patterns of BP change during the first 9 months of anti-hypertensive therapy intensification among 1,331 participants in the Secondary Prevention of Small Subcortical Strokes Trial who were previously randomized to lower BP target (SBP

OBJECTIVES:Research has demonstrated that the association between high blood pressure and outcomes is attenuated among older adults with functional limitations, compared with healthier elders. However, it is not known whether these patterns vary by racial/ethnic group. We evaluated race/ethnicity-specific patterns of effect modification in the association between blood pressure and incident cardiovascular disease (CVD) by functional status. SETTING:We used data from the Multi-Ethnic Study of Atherosclerosis (2002-2004, with an average of 8.8 years of follow-up for incident CVD). We assessed effect modification of systolic blood pressure and cardiovascular outcomes by self-reported physical limitations and by age. PARTICIPANTS:The study included 6117 participants (aged 46 to 87; 40% white, 27% black, 22% Hispanic and 12% Chinese) who did not have CVD at the second study examination (when self-reported physical limitations were assessed). OUTCOME MEASURES:Incident CVD was defined as an incident myocardial infarction, coronary revascularisation, resuscitated cardiac arrest, angina, stroke (fatal or non-fatal) or death from CVD. RESULTS:We observed weaker associations between systolic blood pressure (SBP) and CVD among white adults with physical limitations (incident rate ratio (IRR) per 10 mm Hg higher SBP: 1.09 (95% CI 0.99 to 1.20)) than those without physical limitations (IRR 1.29 (1.19, 1.40); P value for interaction

BACKGROUND:APOL1 genetic variants confer an increased risk for kidney disease. Their associations with cardiovascular disease (CVD) are less certain. We aimed to compare the prevalence of subclinical CVD and incidence of atherosclerotic CVD and heart failure by APOL1 genotypes among self-identified black participants of MESA (Multi-Ethnic Study of Atherosclerosis). METHODS AND RESULTS:Cross-sectional associations of APOL1 genotypes (high-risk=2 alleles; low-risk=0 or 1 allele) with coronary artery calcification, carotid-intimal media thickness, and left ventricular mass were evaluated using logistic and linear regression. Longitudinal associations of APOL1 genotypes with incident myocardial infarction, stroke, coronary heart disease, and congestive heart failure were examined using Cox regression. We adjusted for African ancestry, age, and sex. We also evaluated whether hypertension or kidney function markers explained the observed associations. Among 1746 participants with APOL1 genotyping (mean age 62 years, 55% women, mean cystatin C-based estimated glomerular filtration rate 89 mL/min per 1.73 m2, 12% with albuminuria), 12% had the high-risk genotypes. We found no difference in prevalence or severity of coronary artery calcification, carotid-intimal media thickness, or left ventricular mass by APOL1 genotypes. The APOL1 high-risk group was 82% more likely to develop incident heart failure compared with the low-risk group (95% confidence interval, 1.01-3.28). Adjusting for hypertension (hazard ratio, 1.80; 95% confidence interval, 1.00-3.24) but not markers of kidney function (hazard ratio, 1.86; 95% confidence interval, 1.03-3.35) slightly attenuated this association. The APOL1 high-risk genotypes were not significantly associated with other clinical CVD outcomes. CONCLUSIONS:Among blacks without baseline CVD, the APOL1 high-risk variants may be associated with increased risk for incident heart failure but not subclinical CVD or incident clinical atherosclerotic CVD.

Whether APOL1 polymorphisms contribute to the excess risk of hypertension among blacks is unknown. To assess this we evaluated whether self-reported race and, in blacks, APOL1 risk variants (high-risk [2 risk alleles] versus low-risk [0-1 risk allele]) were associated with longitudinal blood pressure. Blood pressure trajectories were determined using linear mixed-effects (slope) and latent class models (5 distinct groups) during 25 years of follow-up in the Coronary Artery Risk Development in Young Adults Study. Associations of race and APOL1 genotypes with blood pressure change, separately, using linear mixed-effects and multinomial logistic regression models, adjusting for demographic, socioeconomic, and traditional hypertension risk factors, anti-hypertensive medication use, and kidney function were evaluated. Among 1700 whites and 1330 blacks (13% APOL1 high-risk, mean age 25 years; 46% male) mean mid-, ([systolic + diastolic blood pressure]/2), systolic, and diastolic blood pressures were 89, 110, and 69 mm Hg, respectively. One percent of participants used anti-hypertensive medications at baseline. Compared to whites, blacks, regardless of APOL1 genotype, had significantly greater increases in mid-blood pressure and were more likely to experience significantly increasing mid-blood pressure trajectories with adjusted relative risk ratios of 5.21 and 7.27 for moderate-increasing and elevated-increasing versus low-stable blood pressure, respectively. Among blacks, longitudinal mid-blood pressure changes and mid-blood pressure trajectory classification were similar by APOL1 risk status. Modeling systolic and diastolic blood pressure as outcomes yielded similar findings. From young adulthood to mid-life, blacks have greater blood pressure increases versus whites that are not fully explained by traditional risk factors. Thus APOL1 variants are not associated with longitudinal blood pressure in blacks.

BackgroundSome evidence suggests that chronic kidney disease is a risk factor for lower-extremity peripheral artery disease. We aimed to quantify the independent and joint associations of two measures of chronic kidney disease (estimated glomerular filtration rate [eGFR] and albuminuria) with the incidence of peripheral artery disease.MethodsIn this collaborative meta-analysis of international cohorts included in the Chronic Kidney Disease Prognosis Consortium (baseline measurements obtained between 1972 and 2014) with baseline measurements of eGFR and albuminuria, at least 1000 participants (this criterion not applied to cohorts exclusively enrolling patients with chronic kidney disease), and at least 50 peripheral artery disease events, we analysed adult participants without peripheral artery disease at baseline at the individual patient level with Cox proportional hazards models to quantify associations of creatinine-based eGFR, urine albumin-to-creatinine ratio (ACR), and dipstick proteinuria with the incidence of peripheral artery disease (including hospitalisation with a diagnosis of peripheral artery disease, intermittent claudication, leg revascularisation, and leg amputation). We assessed discrimination improvement through c-statistics.FindingsWe analysed 817 084 individuals without a history of peripheral artery disease at baseline from 21 cohorts. 18 261 cases of peripheral artery disease were recorded during follow-up across cohorts (median follow-up was 7·4 years [IQR 5·7-8·9], range 2·0-15·8 years across cohorts). Both chronic kidney disease measures were independently associated with the incidence of peripheral artery disease. Compared with an eGFR of 95 mL/min per 1·73 m2, adjusted hazard ratios (HRs) for incident study-specific peripheral artery disease was 1·22 (95% CI 1·14-1·30) at an eGFR of 45 mL/min per 1·73 m2 and 2·06 (1·70-2·48) at an eGFR of 15 mL/min per 1·73 m2. Compared with an ACR of 5 mg/g, the adjusted HR for incident study-specific peripheral artery disease was 1·50 (1·41-1·59) at an ACR of 30 mg/g and 2·28 (2·12-2·44) at an ACR of 300 mg/g. The adjusted HR at an ACR of 300 mg/g versus 5 mg/g was 3·68 (95% CI 3·00-4·52) for leg amputation. eGFR and albuminuria contributed multiplicatively (eg, adjusted HR 5·76 [4·90-6·77] for incident peripheral artery disease and 10·61 [5·70-19·77] for amputation in eGFR

BackgroundPoor access to food among low-income adults has been recognized as a risk factor for chronic kidney disease (CKD), but there are no data for the impact of food insecurity on progression to end-stage renal disease (ESRD). We hypothesized that food insecurity would be independently associated with risk for ESRD among persons with and without earlier stages of CKD.Study designLongitudinal cohort study.Setting & participants2,320 adults (aged ≥ 20 years) with CKD and 10,448 adults with no CKD enrolled in NHANES III (1988-1994) with household income ≤ 400% of the federal poverty level linked to the Medicare ESRD Registry for a median follow-up of 12 years.PredictorFood insecurity, defined as an affirmative response to the food-insecurity screening question.OutcomeDevelopment of ESRD.MeasurementsDemographics, income, diabetes, hypertension, estimated glomerular filtration rate, and albuminuria. Dietary acid load was estimated from 24-hour dietary recall. We used a Fine-Gray competing-risk model to estimate the relative hazard (RH) for ESRD associated with food insecurity after adjusting for covariates.Results4.5% of adults with CKD were food insecure. Food-insecure individuals were more likely to be younger and have diabetes (29.9%), hypertension (73.9%), or albuminuria (90.4%) as compared with their counterparts (P

BackgroundCommon blood pressure (BP) trajectories are not well established in elderly persons, and their association with clinical outcomes is uncertain.MethodsWe used hierarchical cluster analysis to identify discrete BP trajectories among 4,067 participants in the Cardiovascular Health Study using repeated BP measures from years 0 to 7. We then evaluated associations of each BP trajectory cluster with all-cause mortality, incident cardiovascular disease (CVD, defined as stroke or myocardial infarction) (N = 2,837), and incident congestive heart failure (HF) (N = 3,633) using Cox proportional hazard models.ResultsMedian age was 77 years at year 7. Over a median 9.3 years of follow-up, there were 2,475 deaths, 659 CVD events, and 1,049 HF events. The cluster analysis identified 3 distinct trajectory groups. Participants in cluster 1 (N = 1,838) had increases in both systolic (SBP) and diastolic (DBP) BPs, whereas persons in cluster 2 (N = 1,109) had little change in SBP but declines in DBP. Persons in cluster 3 (N = 1,120) experienced declines in both SBP and DBP. After multivariable adjustment, clusters 2 and 3 were associated with increased mortality risk relative to cluster 1 (hazard ratio = 1.21, 95% confidence interval: 1.06-1.37 and hazard ratio = 1.20, 95% confidence interval: 1.05-1.36, respectively). Compared to cluster 1, cluster 3 had higher rates of incident CVD but associations were not statistically significant in demographic-adjusted models (hazard ratio = 1.16, 95% confidence interval: 0.96-1.39). Findings were similar when stratified by use of antihypertensive therapy.ConclusionsAmong community-dwelling elders, distinct BP trajectories were identified by integrating both SBP and DBP. These clusters were found to have differential associations with outcomes.

BackgroundHigher blood pressure during young adulthood may increase cardiovascular and kidney disease risk later in life. This study examined the association of cumulative systolic blood pressure (SBP) exposure during young adulthood through midlife with urine albumin-to-creatinine ratios (ACR) measured during midlife.MethodsWe used data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a biracial cohort recruited in 4 urban areas during years 1985-1986. Cumulative SBP was calculated as the average SBP between 2 exams multiplied by years between exams over 20 year years. ACR was measured 20 years after baseline when participants were age 43-50 years (midlife). A generalized additive model was used to examine the association of log ACR as a function of cumulative SBP with adjustment for covariates including SBP measured concurrently with ACR.ResultsCumulative SBP ranged from a low of 1,671 to a high of 3,260 mm Hg. Participants in the highest cumulative SBP quartile were more likely to be male (61.4% vs. 20.7%; P < 0.001), Black (61.5% vs. 25.6%; P < 0.001) and have elevated ACR (18.7% vs. 4.8%; P < 0.001) vs. lowest quartile. Spline regression curves of ACR vs. cumulative SBP demonstrated an inflection point in ACR with cumulative SBP levels >2,350 mm Hg with linear increases in ACR above this threshold. Adjusted geometric mean ACR values were significantly higher with cumulative SBP ≥2,500 vs.

BackgroundWhether screening for chronic kidney disease (CKD) can improve the care of persons at high risk for complications remains uncertain. We describe the design and early implementation experience of a pilot, cluster-randomized pragmatic trial to evaluate the feasibility, implementation, and effectiveness of a "triple marker" CKD screening program (creatinine, cystatin C and albumin to creatinine ratio) for improving care among hypertensive veterans seen in primary care at one Veterans Administration Hospital.Methods/designNon-diabetic hypertensive veterans age 18-80 without known CKD were randomized in clusters determined by primary care provider (unit of randomization) into three arms. Usual care will be compared with two incrementally intensified treatment strategies: (1) screen for CKD followed by patient and provider education or (2) screen-educate plus a clinical pharmacist-led CKD and BP management program. The primary clinical outcome is systolic blood pressure (BP) change from baseline. Secondary clinical outcome is BP control. The primary process outcomes is triple marker screening (across three arms), and secondary process outcomes include use of inhibitors of the renin-angiotensin system (ACE/ARB) overall and in persons with albuminuria, CKD recognition by PCP, use of non-steroidal anti-inflammatory drugs (NSAIDs) and NSAID education by PCP. The design uses the Veterans Health Administration electronic health record (EHR) to identify participants, deliver the interventions and ascertain study outcomes. Assessment of the program implementation will use the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. Study duration is 12 months.ResultsA total of 1,819 patients have been randomized within 41 provider clusters. The median age (interquartile range) is 68 years (61-72), and 99% of participants are male. Approximately 16% are Black, and 5% Hispanic. In the first 6 months of the trial, 434 triple marker screening tests have been ordered, and 217(50%) have been tested. A total of 48 new CKD cases have been identified among those tested, for a preliminary yield of 22%.ConclusionWe have successfully implemented a pragmatic protocol that uses the EHR to identify and characterize eligible participants, deliver the intervention, and ascertain study outcomes with high rates of participation by providers and patients. Results from this study can guide design of pragmatic trials in the field of CKD.Trial registrationNCT01978951 ; Date or Registration: 1/17/2014.

Background: Listeria monocytogenes, a Gram-positive intracellular bacillus, causes listeriosis, which is primarily transmitted through contaminated food and vertical transmission. The incidence of the disease is estimated to be between one and ten cases per million globally, with pregnant women being particularly vulnerable. Objective: The aim was to describe the clinical characteristics, management, and outcomes of cases of gestational listeriosis at Hospital Materno Infantil de Málaga in order to improve our understanding, diagnosis, and treatment of this disease. Methods: A retrospective analysis of six confirmed cases of listeriosis was performed in pregnant women or neonates. Diagnostic confirmation was achieved using analytic and microbiological methodologies, including blood cultures and the measurement of C-reactive protein (CRP). Ethical approval was obtained, and clinical data were reviewed for reasons related to consultation, treatment approaches, and complications. Results: The most frequently observed symptoms were fever and abdominal pain, with complications such as intrauterine death and suspected chorioamnionitis. Four patients were treated with antibiotics, leading to improved outcomes. No severe complications such as neurolisteriosis were observed. Conclusions: Pregnant women are more susceptible to L. monocytogenes, which can cause mild maternal symptoms but severe foetal outcomes, including prematurity, foetal death, or neonatal infections. Early diagnosis and prompt treatment are crucial for improving maternal–foetal outcomes. [ABSTRACT FROM AUTHOR]

Subclinical kidney disease is associated with developing hypertension in the general population, but data are lacking among HIV-infected people. We examined associations of kidney function and injury with incident hypertension in 823 HIV-infected and 267 HIV-uninfected women in the Women's Interagency HIV Study, a multicenter, prospective cohort of HIV-infected and uninfected women in the United States. Baseline kidney biomarkers included estimated glomerular filtration rate using cystatin C, urine albumin-to-creatinine ratio, and 7 urine biomarkers of tubular injury: α-1-microglobulin, interleukin-18, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, liver fatty acid-binding protein, N-acetyl-β-d-glucosaminidase, and α1-acid-glycoprotein. We used multivariable Poisson regression to evaluate associations of kidney biomarkers with incident hypertension, defined as 2 consecutive visits of antihypertensive medication use. During a median follow-up of 9.6 years, 288 HIV-infected women (35%) developed hypertension. Among the HIV-infected women, higher urine albumin-to-creatinine ratio was independently associated with incident hypertension (relative risk =1.13 per urine albumin-to-creatinine ratio doubling, 95% confidence interval, 1.07-1.20), as was lower estimated glomerular filtration rate (relative risk =1.10 per 10 mL/min/1.73 m2 lower estimated glomerular filtration rate; 95% confidence interval, 1.04-1.17). No tubular injury and dysfunction biomarkers were independently associated with incident hypertension in HIV-infected women. In contrast, among the HIV-uninfected women, urine albumin-to-creatinine ratio was not associated with incident hypertension, whereas higher urine interleukin-18, α1-acid-glycoprotein, and N-acetyl-β-d-glucosaminidase levels were significantly associated with incident hypertension. These findings suggest that early glomerular injury and kidney dysfunction may be involved in the pathogenesis of hypertension in HIV-infected people. The associations of tubular markers with hypertension in HIV-uninfected women should be validated in other studies.