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Adjudication of inpatient AKI in the Systolic Blood Pressure Intervention Trial (SPRINT) was based on billing codes and admission and discharge notes. The purpose of this study was to evaluate the effect of intensive versus standard BP control on creatinine-based inpatient and outpatient AKI, and whether AKI was associated with cardiovascular disease (CVD) and mortality.We linked electronic health record (EHR) data from 47 clinic sites with trial data to enable creatinine-based adjudication of AKI. Cox regression was used to evaluate the effect of intensive BP control on the incidence of AKI, and the relationship between incident AKI and CVD and all-cause mortality.A total of 3644 participants had linked EHR data. A greater number of inpatient AKI events were identified using EHR data (187 on intensive versus 155 on standard treatment) as compared with serious adverse event (SAE) adjudication in the trial (95 on intensive versus 61 on standard treatment). Intensive treatment increased risk for SPRINT-adjudicated inpatient AKI (HR, 1.51; 95% CI, 1.09 to 2.08) and for creatinine-based outpatient AKI (HR, 1.40; 95% CI, 1.15 to 1.70), but not for creatinine-based inpatient AKI (HR, 1.20; 95% CI, 0.97 to 1.48). Irrespective of the definition (SAE or creatinine based), AKI was associated with increased risk for all-cause mortality, but only creatinine-based inpatient AKI was associated with increased risk for CVD.Creatinine-based ascertainment of AKI, enabled by EHR data, may be more sensitive and less biased than traditional SAE adjudication. Identifying ways to prevent AKI may reduce mortality further in the setting of intensive BP control.

Background Recent evidence has shown that fine particulate matter (PM2.5) may be an important environmental risk factor for chronic kidney disease (CKD), but few studies have examined this association for individual patients using fine spatial data. Objective To investigate the association between PM2.5 and CKD (estimated glomerular filtration rate [eGFR] 10.4), third (10.3

Background Clinic blood pressure (BP) when measured in the seated position, can miss meaningful BP phenotypes, including low ambulatory BP (white coat effects [WCE]) or high supine BP (nocturnal non-dipping). Orthostatic hypotension (OH) measured using both seated (or supine) and standing BP, could identify phenotypes poorly captured by seated clinic BP alone. Methods We examined the association of OH with WCE and night-to-daytime systolic BP (SBP) in a subpopulation of SPRINT, a randomized trial testing the effects of intensive or standard (1. Results Of 897 adults (mean age 71.5±9.5 years, 29% female, 28% black), 128 had OH at least once. Among those with OH, 15% had WCE (vs. 7% without OH). Moreover, 25% of those with OH demonstrated a non-dipping pattern (vs. 14% without OH). OH was positively associated with both WCE (OR=2.24; 95%CI: 1.28, 4.27) and reverse dipping (OR=2.29; 95% CI: 1.31, 3.99). Conclusions The identification of OH in clinic was associated with two BP phenotypes often missed with traditional seated BP assessments. Further studies on mechanisms of these relationships are needed. Clinical trials registration Trial Number NCT03569020.

Introduction For patients on renal replacement therapy (RRT), "travel" and "independence" are rated as 2 of the top 5 factors that inform their choice of treatment modality. While home dialysis modalities offer patients a high degree of independence, the most common RRT in the United States is in-center hemodialysis (IHD). The limits imposed by IHD treatment can present a variety of challenges for patients who wish to travel. This study explored how IHD patients managed their travel and the role of dialysis social workers in executing travel arrangements for patients. Methods We performed a qualitative descriptive investigation using semi-structured interviews with adults receiving IHD (n = 16) and renal social workers (n = 8) from Iowa, Minnesota, North Dakota, South Dakota, and Wisconsin. Data were analyzed using a constant comparative method. Findings Three themes emerged from the interviews: travel process, travel-related barriers, and travel-related facilitators. The travel process entailed transient dialysis unit challenges and the need for multiple preparations and precautions. Barriers included comorbidities and not having a relationship with transient dialysis unit staff. Facilitators focused on the importance of travel and staff professionalism at transient dialysis units. Overall, there was lack of uniform protocols to guide the travel process at the patient and the dialysis unit levels. Discussion This study identified multiple perspectives regarding travel arrangements in chronic IHD patients. There is limited research on travel issues for IHD patients and this investigation is among the first to articulate barriers and facilitators associated with travel from the perspective of patients and social workers. Supporting travel for IHD patients can increase their sense of autonomy and provide opportunities to improve their quality of life.

Background Whether ambulatory BP monitoring is of value in evaluating risk for outcomes in patients with CKD is not clear. Methods We followed 1502 participants of the Chronic Renal Insufficiency Cohort (CRIC) Study for a mean of 6.72 years. We evaluated, as exposures, ambulatory BP monitoring profiles (masked uncontrolled hypertension, white-coat effect, sustained hypertension, and controlled BP), mean ambulatory BP monitoring and clinic BPs, and diurnal variation in BP-reverse dipper (higher at nighttime), nondipper, and dipper (lower at nighttime). Outcomes included cardiovascular disease (a composite of myocardial infarction, cerebrovascular accident, heart failure, and peripheral arterial disease), kidney disease (a composite of ESKD or halving of the eGFR), and mortality. Results Compared with having controlled BP, the presence of masked uncontrolled hypertension independently associated with higher risk of the cardiovascular outcome and the kidney outcome, but not with all-cause mortality. Higher mean 24-hour systolic BP associated with higher risk of cardiovascular outcome, kidney outcome, and mortality, independent of clinic BP. Participants with the reverse-dipper profile of diurnal BP variation were at higher risk of the kidney outcome. Conclusions In this cohort of participants with CKD, BP metrics derived from ambulatory BP monitoring are associated with cardiovascular outcomes, kidney outcomes, and mortality, independent of clinic BP. Masked uncontrolled hypertension and mean 24-hour BP associated with high risk of cardiovascular disease and progression of kidney disease. Alterations of diurnal variation in BP are associated with high risk of progression of kidney disease, stroke, and peripheral arterial disease. These data support the wider use of ambulatory BP monitoring in the evaluation of hypertension in patients with CKD. Podcast This article contains a podcast at https://www.asn-online.org/media/podcast/JASN/2020_09_24_JASN2020030236.mp3.

Background Apparent treatment-resistant hypertension is common in patients with CKD. Whether measurement of 24-hour ambulatory BP monitoring is valuable for risk-stratifying patients with resistant hypertension and CKD is unclear. Methods We analyzed data from the Chronic Renal Insufficiency Cohort study, a prospective study of participants (n=1186) with CKD. Office BP was measured using standardized protocols; ambulatory BP was measured using Spacelabs monitors. Apparent treatment-resistant hypertension was defined on the basis of office BP, ambulatory BP monitoring, and use of more than three antihypertensive medications. Outcomes were composite cardiovascular disease, kidney outcomes, and mortality. Groups were compared using Cox regression analyses with a control group of participants without apparent treatment-resistant hypertension. Results Of 475 participants with apparent treatment-resistant hypertension on the basis of office BP, 91.6% had apparent treatment-resistant hypertension confirmed by ambulatory BP monitoring. Unadjusted event rates of composite cardiovascular disease, kidney outcomes, and mortality were higher in participants with ambulatory BP monitoring–defined apparent treatment-resistant hypertension compared with participants without apparent treatment-resistant hypertension. In adjusted analyses, the risks of composite cardiovascular disease (hazard ratio, 1.27; 95% confidence interval [95% CI], 0.59 to 2.7), kidney outcomes (hazard ratio, 1.68; 95% CI, 0.88 to 3.21), and mortality (hazard ratio, 1.27; 95% CI, 0.5 to 3.25) were not statistically significantly higher in participants with ambulatory BP monitoring–defined apparent treatment-resistant hypertension compared with participants without apparent treatment-resistant hypertension. Conclusions In our study population with CKD, most patients with apparent treatment-resistant hypertension defined on the basis of office BP have apparent treatment-resistant hypertension confirmed by ambulatory BP monitoring. Although ABPM-defined apparent treatment-resistant hypertension was not independently associated with clinical outcomes, it identified participants at high risk for adverse clinical outcomes.

Background and objectives It is unclear whether the presence of albuminuria modifies the effects of intensive systolic BP control on risk of eGFR decline, cardiovascular events, or mortality. Design, setting, participants, & measurements The Systolic Blood Pressure Intervention Trial randomized nondiabetic adults ≥50 years of age at high cardiovascular risk to a systolic BP target of Results Over a median follow-up of 3.1 years, 69 of 1723 (4%) participants with baseline albuminuria developed ≥40% eGFR decline compared with 61 of 7162 (1%) participants without albuminuria. Incidence rates of ≥40% eGFR decline were higher in participants with albuminuria (intensive, 1.74 per 100 person-years; standard, 1.17 per 100 person-years) than in participants without albuminuria (intensive, 0.48 per 100 person-years; standard, 0.11 per 100 person-years). Although effects of intensive BP lowering on ≥40% eGFR decline varied by albuminuria on the relative scale (hazard ratio, 1.48; 95% confidence interval, 0.91 to 2.39 for albumin-creatinine ratio ≥30 mg/g; hazard ratio, 4.55; 95% confidence interval, 2.37 to 8.75 for albumin-creatinine ratio Conclusions Albuminuria did not modify the absolute benefits and risks of intensive systolic BP lowering.

The majority of patients with chronic kidney disease (CKD) have elevated blood pressure (BP). In patients with CKD, hypertension is associated with increased risk for cardiovascular disease, progression of CKD, and all-cause mortality. New guidelines from the American College of Cardiology/American Heart Association (ACC/AHA) recommend new thresholds and targets for the diagnosis and treatment of hypertension in patients with and without CKD. A new aspect of the guidelines is the recommendation for measurement of out-of-office BP to confirm the diagnosis of hypertension and guide therapy. In this KDOQI (Kidney Disease Outcomes Quality Initiative) perspective, we review the recommendations for accurate BP measurement in the office, at home, and with ambulatory BP monitoring. Regardless of location, validated devices and appropriate cuff sizes should be used. In the clinic and at home, proper patient preparation and positioning are critical. Patients should receive information about the importance of BP measurement techniques and be encouraged to advocate for adherence to guideline recommendations. Implementing appropriate BP measurement in routine practice is feasible and should be incorporated in system-wide efforts to improve the care of patients with hypertension. Hypertension is the number 1 chronic disease risk factor in the world; BP measurements in the office, at home, and with ambulatory BP monitoring should adhere to recommendations from the AHA.

Acute kidney injury (AKI) is potentially catastrophic and commonly seen among inpatients. In the United States, the quality of administrative coding data for capturing AKI accurately is questionable and needs to be updated. This retrospective study validated the quality of administrative coding for hospital-acquired AKI and explored the opportunities to improve the phenotyping performance by utilizing additional data sources from the electronic health record (EHR). A total of34570 patients were included, and overall prevalence of AKI based on the KDIGO reference standard was 10.13%, We obtained significantly different quality measures (sensitivity.-0.486, specificity:0.947, PPV.0.509, NPV:0.942 in the full cohort) of administrative coding from the previously reported ones in the U.S. Additional use of clinical notes by incorporating automatic NLP data extraction has been found to increase the AUC in phenotyping AKI, and AKI was better recognized in patients with heart failure, indicating disparities in the coding and management of AKI.

Objective: Robust disease and syndromic surveillance tools are underdeveloped in the United States, as evidenced by limitations and heterogeneity in sociodemographic data collection throughout the COVID-19 pandemic. To monitor the COVID-19 pandemic in Minnesota, we developed a federated data network in March 2020 using electronic health record (EHR) data from 8 multispecialty health systems. Materials and Methods: In this serial cross-sectional study, we examined patients of all ages who received a COVID-19 polymerase chain reaction test, had symptoms of a viral illness, or received an influenza test from January 3, 2016, through November 7, 2020. We evaluated COVID-19 testing rates among patients with symptoms of viral illness and percentage positivity among all patients tested, in aggregate and by zip code. We stratified results by patient and area-level characteristics. Results: Cumulative COVID-19 positivity rates were similar for people aged 12-64 years (range, 15.1%-17.6%) but lower for adults aged ≥65 years (range, 9.3%-10.7%). We found notable racial and ethnic disparities in positivity rates early in the pandemic, whereas COVID-19 positivity was similarly elevated across most racial and ethnic groups by the end of 2020. Positivity rates remained substantially higher among Hispanic patients compared with other racial and ethnic groups throughout the study period. We found similar trends across area-level income and rurality, with disparities early in the pandemic converging over time. Practice Implications: We rapidly developed a distributed data network across Minnesota to monitor the COVID-19 pandemic. Our findings highlight the utility of using EHR data to monitor the current pandemic as well as future public health priorities. Building partnerships with public health agencies can help ensure data streams are flexible and tailored to meet the changing needs of decision makers.

Using vaccine data combined with electronic health records, we report that mRNA boosters provide greater protection than a two-dose regimen against SARS-CoV-2 infection and related hospitalizations. The benefit of a booster was more evident in the elderly and those with comorbidities. These results support the case for COVID-19 boosters.

Using vaccine data combined with electronic health records, we report that mRNA boosters provide greater protection than a 2-dose regimen against SARS-CoV-2 infection and related hospitalizations. The benefit of a booster was more evident in the elderly and those with comorbidities.

Rationale & Objective Risk factors for acute kidney injury (AKI) in the hospital have been well studied. Yet, risk factors for identifying high-risk patients for AKI occurring and managed in the outpatient setting are unknown and may differ. Study Design Predictive model development and external validation using observational electronic health record data. Setting & Participants Patients aged 18-90 years with recurrent primary care encounters, known baseline serum creatinine, and creatinine measured during an 18-month outcome period without established advanced kidney disease. New Predictors & Established Predictors Established predictors for inpatient AKI were considered. Potential new predictors were hospitalization history, smoking, serum potassium levels, and prior outpatient AKI. Outcomes A ≥50% increase in the creatinine level above a moving baseline of the recent measurement(s) without a hospital admission within 7 days defined outpatient AKI. Analytical Approach Logistic regression with bootstrap sampling for backward stepwise covariate elimination was used. The model was then transformed into 2 binary tests: one identifying high-risk patients for research and another identifying patients for additional clinical monitoring or intervention. Results Outpatient AKI was observed in 4,611 (3.0%) and 115,744 (2.4%) patients in the development and validation cohorts, respectively. The model, with 18 variables and 3 interaction terms, produced C statistics of 0.717 (95% CI, 0.710-0.725) and 0.722 (95% CI, 0.720-0.723) in the development and validation cohorts, respectively. The research test, identifying the 5.2% most at-risk patients in the validation cohort, had a sensitivity of 0.210 (95% CI, 0.208-0.213) and specificity of 0.952 (95% CI, 0.951-0.952). The clinical test, identifying the 20% most at-risk patients, had a sensitivity of 0.494 (95% CI, 0.491-0.497) and specificity of 0.806 (95% CI, 0.806-0.807). Limitations Only surviving patients with measured creatinine levels during a baseline period and outcome period were included. Conclusions The outpatient AKI risk prediction model performed well in both the development and validation cohorts in both continuous and binary forms., Graphical abstract

The Kidney Disease Outcomes Quality Initiative (KDOQI) convened a work group to review the 2021 KDIGO (Kidney Disease: Improving Global Outcomes) guideline for the management of blood pressure in chronic kidney disease (CKD). This commentary is the product of that work group and presents the recommendations and practice points from the KDIGO guideline in the context of US clinical practice. A critical addition to the KDIGO guideline is the recommendation for accurate assessment of blood pressure using standardized office blood pressure measurement. In the general adult population with CKD, KDIGO recommends a goal systolic blood pressure less than 120 mm Hg on the basis of results from the Systolic Blood Pressure Intervention Trial (SPRINT) and secondary analyses of the Action to Control Cardiovascular Risk in Diabetes-Blood Pressure (ACCORD-BP) trial. The KDOQI work group agreed with most of the recommendations while highlighting the weak evidence base especially for patients with diabetes and advanced CKD.

AKI is associated with a high rate of mortality in patients managed with VA ECMO after out-of-hospital cardiac arrest. Therapeutic hypothermia is associated with hypokalemia and hypophosphatemia. During rewarming after hypothermia, hyperphosphatemia and hyperkalemia can develop. Electrolyte replacement should be carefully monitored.

Background: We recently demonstrated how orthostatic hypotension might be used to identify out-of-office blood pressure phenotypes, including white coat effects and nocturnal non-dipping patterns. However, these findings have not been replicated in a population with chronic kidney disease (CKD). Objective: To examine the association between orthostatic hypotension (OH) or hypertension (OHTN) with ambulatory BP in adults with CKD. Methods: CRIC is a prospective multicenter observation cohort study of participants with CKD. Standing BP at 1 minute and ABPM were obtained on 1467 participants. OH was defined as a 20mmHg drop in systolic BP (SBP) or 10 mmHg drop in diastolic BP (DBP) when changing from seated to standing positions. OHTN was defined as a 20 mmHg or 10mmHg rise in SBP or DBP respectively when changing from seated to standing position. White coat effects, based on ABPM, was defined as the difference between seated clinic and ambulatory BP. Systolic and diastolic night to day ratio was also calculated. Results: Of the 1467 participants (age: 58 ± 10 yrs, 44% female, 39% black) 73 had OH and 165 had OHTN). OH was positively associated with systolic and diastolic white coat effect (β=5.9 [0.9, 10.9] and 4.2 [1.3, 7.1]). OHTN was negatively associated with diastolic white coat effect (-4.9 [-6.9, -3]). OH was positively associated with systolic and diastolic night-to-day ratio (0.03 [0.01, 0.05] and 0.03 [0.01, 0.06] respectively). Conclusions: Clinic-based assessments of OH and OHTN may be useful for identifying BP phenotypes often missed with seated office BP measurements in CKD patients.

BACKGROUND The association between hypertension (HTN) and inflammatory biomarkers (interleukin-6 [IL-6] and high-sensitivity C-reactive protein [hsCRP]) in HIV-positive persons with CD4+ count >500 cells/mm3 is unknown. METHODS We studied HTN in participants of the Strategic Timing of AntiRetroviral Treatment (START) trial of immediate vs. deferred antiretroviral therapy (ART) in HIV-positive, ART naive adults with CD4+ count > 500 cells/mm3. HTN was defined as having a systolic blood pressure (BP) ≥140 mmHg, a diastolic BP ≥90 mmHg, or using BP-lowering therapy. Logistic and discrete Cox regression models were used to study the association between baseline biomarker levels with prevalent and incident HTN. RESULTS Among 4,249 participants with no history of cardiovascular disease, the median age was 36 years, 55% were nonwhite, and the prevalence of HTN at baseline was 18.9%. After adjustment for race, age, gender, body mass index (BMI), diabetes, smoking, HIV RNA and CD4+ levels, associations of IL-6 and hsCRP with HTN prevalence were not significant (OR per twofold higher:1.10, 95% confidence interval [CI]: 0.99, 1.20 for IL-6 and 1.05, 95% CI: 0.99, 1.10 for hsCRP). Overall incidence of HTN was 6.8 cases/100 person years. In similarly adjusted models, neither IL-6 (Hazard ratios [HR] per twofold higher IL-6 levels: 0.97, 95% CI: 0.88, 1.08) nor hsCRP (HR per twofold higher hsCRP levels: 0.97, 95% CI: 0.92, 1.02) were associated with risk of incident HTN. Associations did not differ by treatment group. Age, race, gender, and BMI were significantly associated with both the prevalence and incidence of HTN. CONCLUSIONS Traditional risk factors and not baseline levels of IL-6 or hsCRP were associated with the prevalence and incidence of HTN in START.

Background Arteriovenous dialysis access, fistulae (AVF) or grafts (AVG), are associated with significant rates of thrombosis. Timely thrombectomy may have a significant impact on immediate and long-term access survival. However, switching to a catheter is associated with higher rates of morbidity and mortality compared with those who have an AVF or AVG. Objectives The goal of this study was to evaluate whether time to thrombectomy increases the risk for loss of dialysis access and subsequent placement of a dialysis catheter at hospital discharge, at 6 months, 12 months, and data at any time after discharge. Methods Using retrospective data, 444 patients were identified as having undergone thrombectomy for dialysis access dysfunction between January 2008 and April 2015, with 122 hospital admissions primarily for thrombectomy. Results The mean age was 60.4 years, 65% were male, and 44.3% had an arteriovenous fistula as their dialysis access. The mean time to thrombectomy was 10.8 hours, and 14 patients utilised a catheter for haemodialysis as primary access upon discharge. After adjustment for prior access intervention, access type, and time to thrombectomy, the adjusted odds ratios (AOR) of a one-day delay in thrombectomy was associated with a twofold increase in requirement for catheter at discharge and at 6 months. This association remained present at any time after discharge. Conclusion In this study of patients cared for within an academic health system, a single day delay in thrombectomy nearly doubled the risk of needing a dialysis catheter at hospital discharge, 6 months, or any time after discharge.

ImportanceThe Systolic Blood Pressure Intervention Trial (SPRINT) showed that intensive blood pressure control reduced cardiovascular morbidity and mortality. However, the legacy effect of intensive treatment is unknown.ObjectiveTo evaluate the long-term effects of randomization to intensive treatment with the incidence of cardiovascular and all-cause mortality approximately 4.5 years after the trial ended.Design, Setting, and ParticipantsIn this secondary analysis of a multicenter randomized clinical trial, randomization began on November 8, 2010, the trial intervention ended on August 20, 2015, and trial close-out visits occurred through July 2016. Patients 50 years and older with hypertension and increased cardiovascular risk but without diabetes or history of stroke were included from 102 clinic sites in the US and Puerto Rico. Analyses were conducted between October 2021 and February 2022.InterventionsRandomization to systolic blood pressure (SBP) goal of less than 120 mm Hg (intensive treatment group; n = 4678) vs less than 140 mm Hg (standard treatment group; n = 4683).Main Outcomes and MeasuresExtended observational follow-up for mortality via the US National Death Index from 2016 through 2020. In a subset of 2944 trial participants, outpatient SBP from electronic health records during and after the trial were examined.ResultsAmong 9361 randomized participants, the mean (SD) age was 67.9 (9.4) years, and 3332 (35.6%) were women. Over a median (IQR) intervention period of 3.3 (2.9-3.9) years, intensive treatment was beneficial for both cardiovascular mortality (hazard ratio [HR], 0.66; 95% CI, 0.49-0.89) and all-cause mortality (HR, 0.83; 95% CI, 0.68-1.01). However, at the median (IQR) total follow-up of 8.8 (8.3-9.3) years, there was no longer evidence of benefit for cardiovascular mortality (HR, 1.02; 95% CI, 0.84-1.24) or all-cause mortality (HR, 1.08; 95% CI, 0.94-1.23). In a subgroup of participants, the estimated mean outpatient SBP among participants randomized to intensive treatment increased from 132.8 mm Hg (95% CI, 132.0-133.7) at 5 years to 140.4 mm Hg (95% CI, 137.8-143.0) at 10 years following randomization.Conclusions and RelevanceThe beneficial effect of intensive treatment on cardiovascular and all-cause mortality did not persist after the trial. Given increasing outpatient SBP levels in participants randomized to intensive treatment following the trial, these results highlight the importance of consistent long-term management of hypertension.Trial RegistrationClinicalTrials.gov Identifier: NCT01206062

Chronic Kidney Disease (CKD) represents a slowly progressive disorder that is typically silent until late stages, but early intervention can significantly delay its progression. We designed a portable and scalable electronic CKD phenotype to facilitate early disease recognition and empower large-scale observational and genetic studies of kidney traits. The algorithm uses a combination of rule-based and machine-learning methods to automatically place patients on the staging grid of albuminuria by glomerular filtration rate (“A-by-G” grid). We manually validated the algorithm by 451 chart reviews across three medical systems, demonstrating overall positive predictive value of 95% for CKD cases and 97% for healthy controls. Independent case-control validation using 2350 patient records demonstrated diagnostic specificity of 97% and sensitivity of 87%. Application of the phenotype to 1.3 million patients demonstrated that over 80% of CKD cases are undetected using ICD codes alone. We also demonstrated several large-scale applications of the phenotype, including identifying stage-specific kidney disease comorbidities, in silico estimation of kidney trait heritability in thousands of pedigrees reconstructed from medical records, and biobank-based multicenter genome-wide and phenome-wide association studies.

BackgroundSuboptimal treatment of hypertension remains a widespread problem, particularly among minorities and socioeconomically disadvantaged groups. We present a health system–based intervention with diverse patient populations using readily available smartphone technology. This intervention is designed to empower patients and create partnerships between patients and their provider team to promote hypertension control.ObjectiveThe mGlide randomized controlled trial is a National Institutes of Health–funded study, evaluating whether a mobile health (mHealth)-based intervention that is an active partnership between interprofessional health care teams and patients results in better hypertension control rates than a state-of-clinical care comparison.MethodsWe are recruiting 450 participants including stroke survivors and primary care patients with elevated cardiovascular disease risk from diverse health systems. These systems include an acute stroke service (n=100), an academic medical center (n=150), and community medical centers including Federally Qualified Health Centers serving low-income and minority (Latino, Hmong, African American, Somali) patients (n=200). The primary aim tests the clinical effectiveness of the 6-month mHealth intervention versus standard of care. Secondary aims evaluate sustained hypertension control rates at 12 months; describe provider experiences of system usability and satisfaction; examine patient experiences, including medication adherence and medication use self-efficacy, self-rated health and quality of life, and adverse event rates; and complete a cost-effectiveness analysis.ResultsTo date, we have randomized 107 participants (54 intervention, 53 control).ConclusionsThis study will provide evidence for whether a readily available mHealth care model is better than state-of-clinical care for bridging the guideline-to-practice gap in hypertension treatment in health systems serving diverse patient populations.Trial RegistrationClinicaltrials.gov NCT03612271; https://clinicaltrials.gov/ct2/show/NCT03612271International Registered Report Identifier (IRRID)DERR1-10.2196/25424

Background: Clinic blood pressure (BP) is measured in the seated position, which can miss important home BP phenotypes such as low ambulatory BP (white coat effects) or high supine BP (nocturnal non-dippers). Orthostatic hypotension (OH) is determined based on BP measurements in both seated (or supine) and standing positions, and thus could theoretically identify these important phenotypes in clinic. Objective: To determine the association of OH with white coat effects or night-to-daytime systolic BP (SBP) Methods: SPRINT was a randomized trial testing the effects of intensive (0.9. Results: Of 897 adults (mean age 71.5 [SD, 9.5] yrs, 28.7% female, 28.0% black), 128 had OH at least once. Among those with OH, 14.8% had white coat effects versus 7.2% among those without OH. Moreover, 68.8% of those with OH demonstrated non-dipping patterns versus only 52.0% of those without OH. OH was positively associated with both white coat effects (OR=2.24; 95% CI: 1.28, 4.27) and higher night-to-daytime SBP (β=0.04; 95% CI: 0.02, 0.06) ( Table ). Conclusions: Clinic-based assessments of OH may be a useful tool for identifying BP phenotypes often missed with traditional seated BP assessments.

Guidelines recommend using out-of-office blood pressure (BP) measurements to confirm the diagnoses of hypertension and in the titration of antihypertensive medication. The prevalence of out-of-office BP phenotypes for an office systolic/diastolic BP goal

We assessed the effect of enhanced recovery after surgery protocol related fluid restriction on kidney function and the incidence of postoperative acute kidney injury and 3-month kidney function.In a retrospectively collected, single institution cohort we studied 296 consecutive patients (146 pre-enhanced recovery after surgery vs 150 enhanced recovery after surgery) who underwent radical cystectomy from 2010 to 2018. The primary outcome was the incidence of postoperative acute kidney injury. Secondary outcomes were length of hospital stay, time to bowel movements, time to tolerate regular diet, postoperative complications and 30-day readmission rate. Study limitations include its retrospective design and relatively modest sample size.We observed an increased rate of postoperative acute kidney injury in patients on the enhanced recovery after surgery protocol (42.7% vs 30.1%, OR 1.725, p=0.025). On multivariate analysis enhanced recovery after surgery protocol remained a significant predictor of acute kidney injury even when controlling for other covariates including baseline kidney function (OR 1.8, 95% CI 1.04-3.30, p=0.036). Patients with postoperative acute kidney injury demonstrated significantly higher odds of stage 3 chronic kidney disease at 3 months even after controlling for baseline renal function (OR 2.5, 95% CI 1.3-4.9, p=0.016).Use of an enhanced recovery after surgery protocol following radical cystectomy was associated with a higher risk of postoperative acute kidney injury in patients who had baseline chronic kidney disease which could be related to the restricted perioperative fluid management mandated by enhanced recovery after surgery. Use of the enhanced recovery after surgery protocol did not impact the length of hospital stay or readmission rates.

Background: Kidney tubulointerstitial fibrosis on biopsy is a strong predictor of chronic kidney disease (CKD) progression, and CKD is associated with elevated risk of cardiovascular disease (CVD). Tubular health is poorly quantified by traditional kidney function measures, including estimated glomerular filtration rate (eGFR) and albuminuria. We hypothesized that urinary biomarkers of tubular injury, inflammation, and repair would be associated with higher risk of CVD and mortality in persons with CKD. Methods: We measured urinary concentrations of interleukin-18 (IL-18), kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, monocyte chemoattractant protein-1, and chitinase-3-like protein-1 (YKL-40) at baseline among 2,377 participants of the Systolic Blood Pressure Intervention Trial who had an eGFR < 60 mL/min/1.73 m2. We used Cox proportional hazards models to evaluate biomarker associations with CVD events and all-cause mortality. Results: At baseline, the mean age of participants was 72 ± 9 years, and eGFR was 48 ± 11 mL/min/1.73 m2. Over a median follow-up of 3.8 years, 305 CVD events (3.6% per year) and 233 all-cause deaths (2.6% per year) occurred. After multivariable adjustment including eGFR, albuminuria, and urinary creatinine, none of the biomarkers showed statistically significant associations with CVD risk. Urinary IL-18 (hazard ratio [HR] per 2-fold higher value, 1.14; 95% CI 1.01–1.29) and YKL-40 (HR per 2-fold higher value, 1.08; 95% CI 1.02–1.14) concentrations were each incrementally associated with higher mortality risk. Associations were similar when stratified by randomized blood pressure arm. Conclusions: Among hypertensive trial participants with CKD, higher urinary IL-18 and YKL-40 were associated with higher risk of mortality, but not CVD.

The accurate measurement of blood pressure (BP) is essential for the diagnosis and management of hypertension. Restricted use of mercury devices, increased use of oscillometric devices, discrepancies between clinic and out-of-clinic BP, and concerns about measurement error with manual BP measurement techniques have resulted in uncertainty for clinicians and researchers. The National Heart, Lung, and Blood Institute of the U.S. National Institutes of Health convened a working group of clinicians and researchers in October 2017 to review data on BP assessment among adults in clinical practice and clinic-based research. In this report, the authors review the topics discussed during a 2-day meeting including the current state of knowledge on BP assessment in clinical practice and clinic-based research, knowledge gaps pertaining to current BP assessment methods, research and clinical needs to improve BP assessment, and the strengths and limitations of using BP obtained in clinical practice for research and quality improvement activities.

Background: Kidney tubular atrophy on biopsy is a strong predictor of chronic kidney disease (CKD) progression, but tubular health is poorly quantified by traditional measures including estimated glomerular filtration rate (eGFR) and albuminuria. We hypothesized that urinary biomarkers of impaired tubule function would be associated with faster eGFR declines in persons with CKD. Methods: We measured baseline urine concentrations of uromodulin, β2-microglobulin (β2m), and α1-microglobulin (α1m) among 2,428 participants of the Systolic Blood Pressure Intervention Trial with an eGFR 2. We used linear mixed models to evaluate biomarker associations with annualized relative change in eGFR, stratified by randomization arm. Results: At baseline, the mean age was 73 ± 9 years and eGFR was 46 ± 11 mL/min/1.73 m2. In the standard blood pressure treatment arm, each 2-fold higher urinary uromodulin was associated with slower % annual eGFR decline (0.34 [95% CI: 0.08, 0.60]), whereas higher urinary β2m was associated with faster % annual eGFR decline (−0.10 [95% CI: −0.18, −0.02]) in multivariable-adjusted models including baseline eGFR and albuminuria. Associations were weaker and did not reach statistical significance in the intensive blood pressure treatment arm for either uromodulin (0.11 [−0.13, 0.35], p value for interaction by treatment arm = 0.045) or β2m (−0.01 [−0.08, 0.08], p value for interaction = 0.001). Urinary α1m was not independently associated with eGFR decline in the standard (0.01 [−0.22, 0.23]) or intensive (0.03 [−0.20, 0.25]) arm. Conclusions: Among trial participants with hypertension and CKD, baseline measures of tubular function were associated with subsequent declines in kidney function, although these associations were diminished by intensive blood pressure control.

BACKGROUND AND OBJECTIVES: Hypertension is highly prevalent in patients with CKD as is cognitive impairment and frailty, but the link between them is understudied. Our objective was to determine the association between ambulatory BP patterns, cognitive function, physical function, and frailty among patients with nondialysis-dependent CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Ambulatory BP readings were obtained on 1502 participants of the Chronic Renal Insufficiency Cohort. We evaluated the following exposures: (1) BP patterns (white coat, masked, sustained versus controlled hypertension) and (2) dipping patterns (reverse, extreme, nondippers versus normal dippers). Outcomes included the following: (1) cognitive impairment scores from the Modified Mini Mental Status Examination of

COVID-19 vaccines are effective, but inequities in vaccine administration and waning immunity may limit vaccine effectiveness.To report statewide trends in vaccine administration and vaccine effectiveness in Minnesota.This cohort study used COVID-19 vaccine data from the Minnesota Immunization Information Connection from October 25, 2020, through October 30, 2021 that were linked with electronic health record (EHR) data from health systems collaborating as part of the Minnesota EHR Consortium (MNEHRC). Participants included individuals who were seen at a participating health system in Minnesota.Individuals were considered fully vaccinated in the second week after receipt of a second dose of a BNT162b2 or mRNA-1273 vaccine or a single dose of an Ad26.COV.2.S vaccine.A completed vaccination series and vaccine breakthrough, defined as either a positive SARS-CoV-2 polymerase chain reaction (PCR) test or a hospital admission the same week or within the 3 weeks following a positive SARS-CoV-2 PCR test. A test-negative design and incident rate ratio were used to evaluate COVID-19 vaccine effectiveness separately for the BNT162b2, mRNA-1273, and Ad26.COV.2.S vaccines. Rurality and social vulnerability index were assessed at the area level.This study included 4 431 190 unique individuals at participating health systems, and 3 013 704 (68%) of the individuals were fully vaccinated. Vaccination rates were lowest among Minnesotans who identified as Hispanic (116 422 of 217 019 [54%]), multiracial (30 066 of 57 412 [52%]), American Indian or Alaska Native (22 190 of 41 437 [54%]), and Black or African American (158 860 of 326 595 [49%]) compared with Minnesotans who identified as Asian or Pacific Islander (159 999 of 210 994 [76%]) or White (2 402 928 of 3 391 747 [71%]). Among individuals aged 19 to 64 years, vaccination rates were lower in rural areas (196 479 of 308 047 [64%]) compared with urban areas (151 541 of 1 951 265 [77%]) and areas with high social vulnerability (544 433 of 774 952 [70%]) compared with areas with low social vulnerability (571 613 of 724 369 [79%]). In the 9 weeks ending October 30, 2021, vaccine effectiveness as assessed by a test-negative design was 33% (95% CI, 30%-37%) for Ad26.COV.2.S; 53% (95% CI, 52%-54%) for BNT162b2; and 66% (95% CI, 65%-67%) for mRNA-1273. For SARS-CoV-2-related hospitalizations, vaccine effectiveness in the 9 weeks ending October 30, 2021, was 78% (95% CI, 75%-81%) for Ad26.COV.2.S; 81% (95% CI, 79%-82%) for BNT162b2; and 81% (95% CI, 79%-82%) for mRNA-1273.This cohort study of data from a Minnesota statewide consortium suggests disparities in vaccine administration and effectiveness. Vaccine effectiveness against infection was lower for Ad26.COV.2.S and BNT162b2 but was associated with protection against SARS-CoV-2-related hospitalizations despite the increased prevalence of the Delta variant in Minnesota.

BACKGROUND: Acute kidney injury (AKI) has been extensively studied in hospital settings. Limited data exist regarding outcomes for patients with outpatient AKI who are not subsequently admitted. We investigated whether outpatient AKI, defined by a 50% increase in creatinine (Cr), is associated with increased mortality and renal events. METHODS: In this retrospective study, outpatient serum Cr values from adults receiving primary care at a health system during an 18-month exposure period were used to categorize patients into one of five groups (no outpatient AKI, outpatient AKI with recovery, outpatient AKI without recovery, outpatient AKI without repeat Cr and no Cr). Principal outcomes of all-cause mortality and renal events (50% decline in estimated glomerular filtration rate to

Patients with CKD typically have hypertension. Manual BP measurement in the office setting was used to define hypertension, establish eligibility, and assess BP targets in the epidemiologic studies and early randomized, controlled trials that inform current management of hypertension. Use of automated oscillometric devices has largely replaced manual BP measurement in the office and clinical trials. These newer devices may reduce the white coat effect and facilitate guideline-adherent measurement protocols. Obtaining BP measurements outside of the office with home and ambulatory BP monitoring is now more common. Out of office BPs are especially important in patients with CKD, because reduced GFR and proteinuria are associated with masked hypertension (normal office BP and elevated BP outside of the office), elevated nighttime BP, and abnormal diurnal variation in BP, all of which are associated with higher risk for target organ damage and adverse outcomes. Also, it is now feasible to routinely measure central BP and central hemodynamics. These measures are of greater importance to patients with CKD given the higher prevalence of increased sympathetic tone, arteriosclerosis, and inflammation as well as impaired sodium excretion and endothelial dysfunction, which lead to alterations in central BPs in this population. In this review, we describe various BP measurement techniques and how they apply to the care of patients with CKD.

In patients with chronic kidney disease (CKD), clinical interest often centers on determining treatments and exposures that are causally related to renal progression. Analyses of longitudinal clinical data in this population are often complicated by clinical competing events, such as end-stage renal disease (ESRD) and death, and time-dependent confounding, where patient factors that are predictive of later exposures and outcomes are affected by past exposures. We developed multistate marginal structural models (MS-MSMs) to assess the effect of time-varying systolic blood pressure on disease progression in subjects with CKD. The multistate nature of the model allows us to jointly model disease progression characterized by changes in the estimated glomerular filtration rate (eGFR), the onset of ESRD, and death, and thereby avoid unnatural assumptions of death and ESRD as noninformative censoring events for subsequent changes in eGFR. We model the causal effect of systolic blood pressure on the probability of transitioning into 1 of 6 disease states given the current state. We use inverse probability weights with stabilization to account for potential time-varying confounders, including past eGFR, total protein, serum creatinine, and hemoglobin. We apply the model to data from the Chronic Renal Insufficiency Cohort Study, a multisite observational study of patients with CKD.

BACKGROUND AND OBJECTIVES: Short-term BP variability (derived from 24-hour ambulatory BP monitoring) and long-term BP variability (from clinic visit to clinic visit) are directly related to risk for cardiovascular events, but these relationships have been scarcely investigated in patients with CKD, and their prognostic value in this population is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a cohort of 402 patients with CKD, we assessed associations of short- and long-term systolic BP variability with a composite end point of death or cardiovascular event. Variability was defined as the standard deviation of observed BP measurements. We further tested the prognostic value of these parameters for risk discrimination and reclassification. RESULTS: Mean ± SD short-term systolic BP variability was 12.6±3.3 mm Hg, and mean ± SD long-term systolic BP variability was 12.7±5.1 mm Hg. For short-term BP variability, 125 participants experienced the composite end point over a median follow-up of 4.8 years (interquartile range, 2.3–8.6 years). For long-term BP variability, 110 participants experienced the composite end point over a median follow-up of 3.2 years (interquartile range, 1.0–7.5 years). In adjusted analyses, long-term BP variability was significantly associated with the composite end point (hazard ratio, 1.24; 95% confidence interval, 1.01 to 1.51 per 5-mm Hg higher SD of office systolic BP), but short-term systolic BP variability was not (hazard ratio, 0.92; 95% confidence interval, 0.68 to 1.25 per 5-mm Hg higher SD of 24-hour ambulatory systolic BP). Neither estimate of BP variability improved risk discrimination or reclassification compared with a simple risk prediction model. CONCLUSIONS: In patients with CKD, long-term but not short-term systolic BP variability is related to the risk of death and cardiovascular events. However, BP variability has a limited role for prediction in CKD.

RATIONALE & OBJECTIVE: Screening for chronic kidney disease (CKD) is recommended for patients with diabetes and hypertension as stated by the respective professional societies. However, CKD, a silent disease usually detected at later stages, is associated with low socioeconomic status (SES). We assessed whether adding census tract SES status to the standard screening approach improves our ability to identify patients with CKD. STUDY DESIGN: Screening test analysis. SETTINGS & PARTICIPANTS: Electronic health records (EHR) of 256,162 patients seen at a health care system in the 7-county Minneapolis/St. Paul area and linked census tract data. EXPOSURE: The first quartile of census tract SES (median value of owner-occupied housing units 25 years of age with a bachelor’s degree or higher 30 mg/g, or urinary protein-creatinine ratio >150 mg/g, or urinary analysis [albuminuria] >30 mg/d). ANALYTICAL APPROACH: Sensitivity, specificity, and number needed to screen (NNS) to detect CKD if we screened patients who had hypertension and/or diabetes and/or who lived in low-SES tracts (belonging to the first quartile of any of the 3 measures of tract SES) versus the standard approach. RESULTS: CKD was prevalent in 13% of our cohort. Sensitivity, specificity, and NNS of detecting CKD after adding tract SES to the screening approach were 67% (95% CI, 66.2%−67.2%), 61% (95% CI, 61.1%−61.5%), and 5, respectively. With the standard approach, sensitivity of detecting CKD was 60% (95% CI, 59.4%−60.4%), specificity was 73% (95% CI, 72.4%−72.7%), and NNS was 4. LIMITATIONS: One health care system and selection bias. CONCLUSIONS: Leveraging patients’ addresses from the EHR and adding tract-level SES to the standard screening approach modestly increases the sensitivity of detecting patients with CKD at a cost of decreased specificity. Identifying further factors that improve CKD detection at an early stage are needed to slow the progression of CKD and prevent cardiovascular complications.

Hypertension is common in patients with chronic kidney disease (CKD) and contributes to risk of progression of CKD and cardiovascular disease. Many factors including alterations in salt and water balance, the sympathetic nervous system, and the renin–angiotensin–aldosterone system underlie the pathophysiology of hypertension in this setting. Careful measurement of blood pressure, including out-of-office measurement, is important. Goal blood pressure for patients with CKD is less than 130/80 mm Hg. Restriction of dietary salt intake is an important nonpharmacologic intervention, and inhibitors of the renin–angiotensin axis are the cornerstone of drug therapy, especially in patients with proteinuria.