Search

Background: Nighttime blood pressure (BP) has greater prognostic importance for cardiovascular disease (CVD) than daytime BP, but less is known about nighttime and daytime BP associations with measures of subclinical CVD., Methods: Among 897 Systolic Blood Pressure Intervention Trial Study (SPRINT) participants with 24-hour ambulatory BP monitoring obtained near the 27-month study visit, 849 (95%) had N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) measured at the 24-month study visit. Multivariable linear regression analyses were performed to evaluate the associations of nighttime and daytime BP with cardiac biomarker levels., Results: The mean age was 69 ± 12 years, 28% were African American, and mean nighttime and daytime SBP were 121 ± 16 mm Hg and 132 ± 14 mm Hg, respectively. In multivariable models, compared with the lowest tertile of nighttime systolic BP, the highest tertile was associated with 48% higher NT-proBNP levels (adjusted geometric mean ratio [GMR] = 1.48, 95% CI: 1.22, 1.79), and 19% higher hs-cTnT levels (adjusted GMR = 1.19, 95% CI: 1.07, 1.32). In contrast, the highest vs. lowest tertile of daytime systolic BP was not associated with NT-proBNP (adjusted GMR = 1.09, 95% CI: 0.88, 1.34), but was associated with 16% higher hs-cTnT levels (adjusted GMR = 1.16, 95% CI: 1.04, 1.30). Similar results were observed using diastolic BP., Conclusions: In SPRINT, both higher nighttime and daytime BP were independently associated with higher hs-cTnT levels, but only higher nighttime BP was associated with higher NT-proBNP levels., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce the risk for several adverse outcomes among patients with diabetic kidney disease. Yet, optimal timing for SGLT2i after acute kidney injury (AKI) is uncertain, as are the providers responsible for post-AKI SGLT2i initiation. Using a retrospective cohort of United States Veterans with diabetes mellitus type 2 and proteinuria, we examined encounters by provider specialty before SGLT2i initiation and subsequent all-cause mortality after hospitalization with AKI, defined by a 50% or more rise in serum creatinine. Covariates included recovery, defined by return to a 110% or less of baseline creatinine, and time since AKI hospitalization. Among 21,330 eligible Veterans, 7,798 died (37%) and 6,562 received a SGLT2i (31%) over median follow-up of 2.1 years. Post-AKI SGLT2i use was associated with lower mortality risk [adjusted hazard ratio 0.63 (95% confidence interval 0.58-0.68)]. Compared with neither SGLT2i use nor recovery, mortality risk was similar with recovery without SGLT2i use [0.97 (0.91-1.02)] but was lower without recovery prior to SGLT2i use [0.62 (0.55-0.71)] and with SGLT2i use after recovery [0.60 (0.54-0.67)]. Finally, the effect of SGLT2i was stable over time (P for time-interaction 0.19). Thus, we observed reduced mortality with SGLT2i use after AKI among Veterans with diabetic kidney disease whether started earlier or later or before or after observed recovery. Hence, patients with diabetic kidney disease who receive a SGLT2i earlier after AKI experience no significant harm impacting mortality and experience a lower mortality risk than those who do not., (Copyright © 2024 International Society of Nephrology. All rights reserved.)

COVID-19 disproportionately affects people experiencing homelessness or incarceration. While homelessness or incarceration alone may not impact vaccine effectiveness, medical comorbidities along with social conditions associated with homelessness or incarceration may impact estimated vaccine effectiveness. COVID-19 vaccines reduce rates of hospitalization and death; vaccine effectiveness (VE) against severe outcomes in people experiencing homelessness or incarceration is unknown. We conducted a retrospective, observational cohort study evaluating COVID-19 vaccine VE against SARS-CoV-2 related hospitalization (positive SARS-CoV-2 molecular test same week or within 3 weeks prior to hospital admission) among patients who had experienced homelessness or incarceration. We utilized data from 8 health systems in the Minnesota Electronic Health Record Consortium linked to data from Minnesota's immunization information system, Homeless Management Information System, and Department of Corrections. We included patients 18 years and older with a history of experiencing homelessness or incarceration. VE and 95% Confidence Intervals (CI) against SARS-CoV-2 hospitalization were estimated for primary series and one booster dose from Cox proportional hazard models as 100*(1-Hazard Ratio) during August 26, 2021, through October 8, 2022 adjusting for patient age, sex, comorbid medical conditions, and race/ethnicity. We included 80,051 individuals who had experienced homelessness or incarceration. Adjusted VE was 52% (95% CI, 41-60%) among those 22 weeks or more since their primary series, 66% (95% CI, 53-75%) among those less than 22 weeks since their primary series, and 69% (95% CI: 60-76%) among those with one booster. VE estimates were consistently lower during the Omicron predominance period compared with the combined Omicron and Delta periods. Despite higher exposure risk, COVID-19 vaccines provided good effectiveness against SARS-CoV-2 related hospitalizations in persons who have experienced homelessness or incarceration., (© 2023. The Author(s).)

Chronic kidney disease (CKD) represents a significant global burden. Hypertension is a modifiable risk factor for rapid progression of CKD. We extend the risk stratification by introducing the non-parametric determination of rhythmic components in 24-h profiles of ambulatory blood pressure monitoring (ABPM) in the Chronic Renal Insufficiency Cohort (CRIC) and the African American Study for Kidney Disease and Hypertension (AASK) cohort using Cox proportional hazards models. We find that rhythmic profiling of BP through JTK_CYCLE analysis identifies subgroups of CRIC participants that were more likely to die due to cardiovascular causes. While our fully adjusted model shows a trend towards a significant association between absent cyclic components and cardiovascular death in the full CRIC cohort (HR: 1.71,95% CI: 0.99-2.97, p = 0.056), CRIC participants with a history of cardiovascular disease (CVD) and absent cyclic components in their BP profile had at any time a 3.4-times higher risk of cardiovascular death than CVD patients with cyclic components present in their BP profile (HR: 3.37, 95% CI: 1.45-7.87, p = 0.005). This increased risk was not explained by the dipping or non-dipping pattern in ABPM. Due to the large differences in patient characteristics, the results do not replicate in the AASK cohort. This study suggests rhythmic blood pressure components as a potential novel biomarker to unmask excess risk among CKD patients with prior cardiovascular disease., (© 2024. The Author(s).)

Background: Intensive BP lowering in the Systolic Blood Pressure Intervention Trial (SPRINT) produced acute decreases in kidney function and higher risk for AKI. We evaluated the effect of intensive BP lowering on long-term changes in kidney function using trial and outpatient electronic health record (EHR) creatinine values., Methods: SPRINT data were linked with EHR data from 49 (of 102) study sites. The primary outcome was the total slope of decline in eGFR for the intervention phase and the post-trial slope of decline during the observation phase using trial and outpatient EHR values. Secondary outcomes included a ≥30% decline in eGFR to <60 ml/min per 1.73 m 2 and a ≥50% decline in eGFR or kidney failure among participants with baseline eGFR ≥60 and <60 ml/min per 1.73 m 2 , respectively., Results: EHR creatinine values were available for a median of 8.3 years for 3041 participants. The total slope of decline in eGFR during the intervention phase was -0.67 ml/min per 1.73 m 2 per year (95% confidence interval [CI], -0.79 to -0.56) in the standard treatment group and -0.96 ml/min per 1.73 m 2 per year (95% CI, -1.08 to -0.85) in the intensive treatment group ( P < 0.001). The slopes were not significantly different during the observation phase: -1.02 ml/min per 1.73 m 2 per year (95% CI, -1.24 to -0.81) in the standard group and -0.85 ml/min per 1.73 m 2 per year (95% CI, -1.07 to -0.64) in the intensive group. Among participants without CKD at baseline, intensive treatment was associated with higher risk of a ≥30% decline in eGFR during the intervention (hazard ratio, 3.27; 95% CI, 2.43 to 4.40), but not during the postintervention observation phase. In those with CKD at baseline, intensive treatment was associated with a higher hazard of eGFR decline only during the intervention phase (hazard ratio, 1.95; 95% CI, 1.03 to 3.70)., Conclusions: Intensive BP lowering was associated with a steeper total slope of decline in eGFR and higher risk for kidney events during the intervention phase of the trial, but not during the postintervention observation phase., (Copyright © 2023 by the American Society of Nephrology.)

Background: Orthostatic changes in blood pressure (BP), either orthostatic hypotension or orthostatic hypertension (OHTN), are common among patients with chronic kidney disease. Whether they are associated with unique out-of-office BP phenotypes is unknown., Methods: CRIC is a prospective, multicenter, observational cohort study of participants with CKD. BP measured at 2 min after standing and ambulatory BP monitoring (ABPM) were obtained on 1386 participants. Orthostatic hypotension was defined as a 20 mmHg drop in SBP or 10 mmHg drop in DBP when changing from seated to standing positions. Systolic and diastolic night-to-day ratio was also calculated. OHTN was defined as a 20 or 10 mmHg rise in SBP or DBP when changing from a seated to a standing position. White-coat effect (WCE) was defined as seated minus daytime ambulatory BP., Results: Of the 1386 participants (age: 58 ± 10 years, 44% female, 39% black), 68 had orthostatic hypotension and 153 had OHTN. Postural reduction in SBP or DBP was positively associated with greater systolic and diastolic WCE and systolic and diastolic night-to-day ratio. Orthostatic hypotension was positively associated with diastolic WCE (β = 3 [0.2, 5.9]). Diastolic OHTN was negatively associated with systolic WCE (β = -4 [-7.2, -0.5]) and diastolic WCE (β = -6 [-8.1, -4.2])., Conclusion: Postural change in BP was associated with WCE and night-to-day-ratio. Orthostatic hypotension was positively associated with WCE and OHTN was negatively associated with WCE. These findings strengthen observations that postural changes in BP may associate with distinct BP patterns throughout the day. These observations are informative for subsequent research tailoring orthostatic hypotension and OHTN treatment to specific BP phenotypes., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Recurrent AKI has been found common among hospitalized patients after discharge, and early prediction may allow timely intervention and optimized post-discharge treatment [1]. There are significant gaps in the literature regarding the risk prediction on the post-AKI population, and most current works only included a limited number of pre-selected variables [2]. In this study, we built and compared machine learning models using both knowledge-based and data-driven features in predicting the risk of recurrent AKI within 1-year of discharge. Our results showed that the additional use of data-driven features statistically improved the model performances, with best AUC=0.766 by using logistic regression.

Significance Statement: Among patients with CKD, optimal use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers after AKI is uncertain. Despite these medications' ability to reduce risk of mortality and other adverse outcomes, there is concern that ACEi/ARB use may delay recovery of kidney function or precipitate recurrent AKI. Prior studies have provided conflicting data regarding the optimal timing of these medications after AKI and have not addressed the role of kidney recovery in determining appropriate timing. This study in US Veterans with diabetes mellitus and proteinuria demonstrated an association between ACEi/ARB use and lower mortality. This association was more pronounced with earlier post-AKI ACEi/ARB use and was not meaningfully affected by initiating ACEis/ARBs before versus after recovery from AKI., Background: Optimal use of angiotensin-converting enzyme inhibitors (ACEis) or angiotensin II receptor blockers (ARBs) after AKI is uncertain., Methods: Using data derived from electronic medical records, we sought to estimate the association between ACEi/ARB use after AKI and mortality in US military Veterans with indications for such treatment (diabetes and proteinuria) while accounting for AKI recovery. We used ACEi/ARB treatment after hospitalization with AKI (defined as serum creatinine ≥50% above baseline concentration) as a time-varying exposure in Cox models. The outcome was all-cause mortality. Recovery was defined as return to ≤110% of baseline creatinine. A secondary analysis focused on ACEi/ARB use relative to AKI recovery (before versus after)., Results: Among 54,735 Veterans with AKI, 31,146 deaths occurred over a median follow-up period of 2.3 years. Approximately 57% received an ACEi/ARB <3 months after hospitalization. In multivariate analysis with time-varying recovery, post-AKI ACEi/ARB use was associated with lower risk of mortality (adjusted hazard ratio [aHR], 0.74; 95% confidence interval [CI], 0.72 to 0.77). The association between ACEi/ARB use and mortality varied over time, with lower mortality risk associated with earlier initiation ( P for interaction with time <0.001). In secondary analysis, compared with those with neither recovery nor ACEi/ARB use, risk of mortality was lower in those with recovery without ACEi/ARB use (aHR, 0.90; 95% CI, 0.87 to 0.94), those without recovery with ACEi/ARB use (aHR, 0.69; 95% CI, 0.66 to 0.72), and those with ACEi/ARB use after recovery (aHR, 0.70; 95% CI, 0.67 to 0.73)., Conclusions: This study demonstrated lower mortality associated with ACEi/ARB use in Veterans with diabetes, proteinuria, and AKI, regardless of recovery. Results favored earlier ACEi/ARB initiation., (Copyright © 2023 by the American Society of Nephrology.)

Background: Prior studies associating acute kidney injury (AKI) with more rapid subsequent loss of kidney function had methodological limitations, including inadequate control for differences between patients who had AKI and those who did not., Objective: To determine whether AKI is independently associated with subsequent kidney function trajectory among patients with chronic kidney disease (CKD)., Design: Multicenter prospective cohort study., Setting: United States., Participants: Patients with CKD ( n  = 3150)., Measurements: Hospitalized AKI was defined by a 50% or greater increase in inpatient serum creatinine (SCr) level from nadir to peak. Kidney function trajectory was assessed using estimated glomerular filtration rate (eGFR) based on SCr level (eGFRcr) or cystatin C level (eGFRcys) measured at annual study visits., Results: During a median follow-up of 3.9 years, 433 participants had at least 1 AKI episode. Most episodes (92%) had stage 1 or 2 severity. There were decreases in eGFRcr (-2.30 [95% CI, -3.70 to -0.86] mL/min/1.73 m 2 ) and eGFRcys (-3.61 [CI, -6.39 to -0.82] mL/min/1.73 m 2 ) after AKI. However, in fully adjusted models, the decreases were attenuated to -0.38 (CI, -1.35 to 0.59) mL/min/1.73 m 2 for eGFRcr and -0.15 (CI, -2.16 to 1.86) mL/min/1.73 m 2 for eGFRcys, and the CI bounds included the possibility of no effect. Estimates of changes in eGFR slope after AKI determined by either SCr level (0.04 [CI, -0.30 to 0.38] mL/min/1.73 m 2 per year) or cystatin C level (-0.56 [CI, -1.28 to 0.17] mL/min/1.73 m 2 per year) also had CI bounds that included the possibility of no effect., Limitations: Few cases of severe AKI, no adjudication of AKI cause, and lack of information about nephrotoxic exposures after hospital discharge., Conclusion: After pre-AKI eGFR, proteinuria, and other covariables were accounted for, the association between mild to moderate AKI and worsening subsequent kidney function in patients with CKD was small., Primary Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M22-3617.

Background: Randomized trials are the gold standard for generating clinical practice evidence, but follow-up and outcome ascertainment are resource-intensive. Electronic health record (EHR) data from routine care can be a cost-effective means of follow-up, but concordance with trial-ascertained outcomes is less well-studied., Methods: We linked EHR and trial data for participants of the Systolic Blood Pressure Intervention Trial (SPRINT), a randomized trial comparing intensive and standard blood pressure targets. Among participants with available EHR data concurrent to trial-ascertained outcomes, we calculated sensitivity, specificity, positive predictive value, and negative predictive value for EHR-recorded cardiovascular disease (CVD) events, using the gold standard of SPRINT-adjudicated outcomes (myocardial infarction (MI)/acute coronary syndrome (ACS), heart failure, stroke, and composite CVD events). We additionally compared the incidence of non-CVD adverse events (hyponatremia, hypernatremia, hypokalemia, hyperkalemia, bradycardia, and hypotension) in trial versus EHR data., Results: 2468 SPRINT participants were included (mean age 68 (SD 9) years; 26% female). EHR data demonstrated ≥80% sensitivity and specificity, and ≥ 99% negative predictive value for MI/ACS, heart failure, stroke, and composite CVD events. Positive predictive value ranged from 26% (95% CI; 16%, 38%) for heart failure to 52% (95% CI; 37%, 67%) for MI/ACS. EHR data uniformly identified more non-CVD adverse events and higher incidence rates compared with trial ascertainment., Conclusions: These results support a role for EHR data collection in clinical trials, particularly for capturing laboratory-based adverse events. EHR data may be an efficient source for CVD outcome ascertainment, though there is clear benefit from adjudication to avoid false positives., Competing Interests: Declaration of Competing Interest CDC receives research support from Bayer Healthcare, Inc. outside the submitted work. AM reports ownership interest in iEnroll, LLC. The remaining authors have nothing to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Remdesivir has been widely used for the treatment of Coronavirus (COVID) in hospitalized patients, but its nephrotoxicity is still under investigation 1 . Given the paucity of knowledge regarding the mechanism and optimal treatment of the development of acute kidney injury (AKI) in the setting of COVID, we analyzed the role of remdesivir and built multifactorial causal models of COVID-AKI by applying causal discovery machine learning techniques. Risk factors of COVID-AKI and renal function measures were represented in a temporal sequence using longitudinal data from EHR. Our models successfully recreated known causal pathways to changes in renal function and interactions with each other and examined the consistency of high-level causal relationships over a 4-day course of remdesivir. Results indicated a need for assessment of renal function on day 2 and 3 use of remdesivir, while uncovering that remdesivir may pose less risk to AKI than existing conditions of chronic kidney disease., (©2022 AMIA - All rights reserved.)

Rationale & Objective: Chronic kidney disease (CKD) is a prevalent condition with high mortality rates. Cardiovascular disease (CVD) is accepted as the leading cause of death in CKD, but data are limited, and no study has evaluated the cause of death in those with progressive CKD versus stable kidney function., Study Design: Retrospective cohort., Setting & Participants: Adults receiving primary care at M Health Fairview (MHFV) after December 31, 2012, with linked Minnesota Death Index data before December 31, 2019, were included. A second cohort was created from adult participants in the 1996-2006 National Health and Nutrition Examination Survey (NHANES) linked with the National Death Index through 2015. Individuals with kidney replacement therapy at baseline were excluded., Exposures: Estimated glomerular filtration rate (eGFR) and proteinuria assessed at baseline defined the exposure categories for MHFV and NHANES. CKD progression in MHFV was also defined as an eGFR decrease ≥30% from baseline or incident kidney replacement therapy., Outcome: CVD-, malignancy-, and dementia-attributed death., Analytical Approach: Multinomial logistic regression., Results: For both cohorts, CVD death was more common than malignancy death for those with eGFR <60 mL/min/1.73 m 2 , whereas the converse was true for those with higher eGFR without proteinuria. In NHANES, CVD deaths were higher in those with proteinuria and eGFR ≥60 mL/min/1.73 m 2 . CKD progression in MHFV had a limited impact on the association with the cause of death except on dementia deaths, which were less common with progression at several stages of CKD. Proteinuria had limited impact on the association with the cause of death across a range of eGFR levels., Limitations: Limited follow-up and, for MHFV, nonprotocolized measures of kidney function were limitations, as were the intrinsic accuracy limitations for death certificates., Conclusions: CVD death is the most significant cause of death observed for those with a reduced eGFR irrespective of CKD progression.

Importance: The 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., Objective: To 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 Participants: In 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., Interventions: Randomization 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 Measures: Extended 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., Results: Among 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 Relevance: The 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 Registration: ClinicalTrials.gov Identifier: NCT01206062.

Competing Interests: All authors have nothing to disclose.

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., Competing Interests: Potential conflicts of interest. A. B. K. and M. D. report funding from the Centers for Disease Control and Prevention (VISION grant, subcontract from HealthPartners Research Institute). V. M. reports funding from Janssen Pharmaceuticals for participation in the COVID-19 vaccine ENSEMBLE clinical trial. R. A. D. reports funding from the US Department of Veterans Affairs, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute and an unpaid leadership or fiduciary role for the National Academy of Medicine, Minneapolis Veterans Affairs Medical Center, and Hennepin County Medical Center. S. W. reports being member and past chair of the governing board for the Health Care Systems Research Network, member of the board of directors for the American College of Epidemiology, member of the board for the Epidemiology Foundation, and member of the Advisory Council in Aging (Area Agency on Aging). All other authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Recent evidence has shown that fine particulate matter (PM 2.5 ) 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 PM 2.5 and CKD (estimated glomerular filtration rate [eGFR]<45 ml/min/1.73 m 2 ) in the Twin-Cities area in Minnesota using a large electronic health care database (2012-2019)., Methods: We estimated the previous 1-year average PM 2.5 from the first eGFR (measured with the CKD Epidemiology Collaboration equation using the first available creatinine measure during the baseline period [2012-2014]) using Environmental Protection Agency downscaler modeling data at the census tract level. We evaluated the spatial relative risk and clustering of CKD prevalence using a K-function test statistic. We assessed the prevalence ratio of the PM 2.5 association with CKD incidence using a mixed effect Cox model, respectively., Results: Patients (n = 20,289) in the fourth (PM 2.5  > 10.4), third (10.3 < PM 2.5  < 10.8) and second quartile (9.9 < PM 2.5  < 10.3) vs. the first quartile (<9.9 μg/m 3 ) had a 2.52[2.21, 2.87], 2.18[1.95, 2.45], and 1.72[1.52, 1.97] hazard rate of developing CKD in the fully adjusted models, respectively. We identified spatial heterogeneities and evidence of CKD clustering across our study region, but this spatial variation was accounted for by air pollution and individual covariates., Significance: Exposure to higher PM 2.5 is associated with a greater risk for incident CKD. Improvements in air quality, specifically at hotspots, may reduce CKD., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

We used data from a statewide public health-health system collaboration to describe trends in COVID-19 vaccination rates by racial and ethnic groups among people experiencing homelessness or incarceration in Minnesota. Vaccination completion rates among the general population and people incarcerated in state prisons were substantially higher than those among people experiencing homelessness or jail incarceration.

Background: 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., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: A.K. Agarwal reports serving in an advisory or leadership role for American Society of Diagnostic and Interventional Nephrology (ASDIN), Clinical Nephrology, International Journal of Nephrology, International Society of Nephrology (ISN), Journal of Vascular Access, Kidney Self-Assessment Program, National Kidney Foundation (NKF), and The Open Urology and Nephrology Journal; having other interests in, or relationships with, the American Society of Nephrology, ASDIN, ISN, and NKF; serving on a speakers bureau for AstraZeneca; having consultancy agreements with, and receiving honoraria from, AstraZeneca and Otsuka Pharmaceuticals. S. Beddhu reports receiving research funding from Bayer, Boehringer Ingelheim, and Novartis; having consultancy agreements with Bayer and Reata; and serving in an advisory or leadership role for CJASN and Kidney Reports. M. Dobre reports receiving honoraria from Relypsa and Tricida; and serving in an advisory or leadership role for Relypsa (Resistant Hypertension Working Group) and Tricida (Metabolic Acidosis Working Group). J.P. Dwyer reports having consultancy agreements with Acuta Capital, Akcea, Aleon, Ardelyx, AstraZeneca, Aurinia, Axsome, Bayer, BioRasi, BioVie, Boeringher Ingelheim, Botanix, Caladrius, Cincor, Contrafect, Cumberland, Eli Lilly, ES, Fibrogen, Genentech, Hope Pharma, Icon, Ionis, Innovative Renal Care, Keros, LifeSci Venture, Medpace, MicuRx, PSI, Rarestone, Reata, RenalytixAI, Sanofi, Spero, Tricida, ValenzaBio, and Worldwide Clinical Trials; having ownership interest in BioRasi, Innovative Renal Care, PathEx, ValenzaBio, and Venostent; serving in an advisory or leadership role for Collaborative Study Group (board of directors and president) and The Bolles School (high school in Jacksonville, FL; board of directors); and having other interests in, or relationships with, The Bolles School Board of Visitors. E. Horwitz reports having other interests in, or relationships with, MetroHealth Medical Center, contracted with Fresenius Kidney Care (serving as medical director for inpatient dialysis services). J. Lash reports serving in an advisory or leadership role for Kidney360. A. McWilliams reports having ownership interest in iEnroll. S. Oparil reports receiving research funding from Bayer (site principal investigator [PI] in diabetic kidney disease), CinCor Pharma (site PI for primary aldosterone study), George Clinical (site PI for GMRx2 treatment of hypertension), and Higi (site PI for BP validation study); having ownership interest in CinCor Pharma; serving in an advisory or leadership role for CinCor Pharma (scientific advisory board for primary aldosteronism and hypertension) and Preventric Diagnostics (chair medical and technology committee; from March 2019 to present); and serving as editor-in-chief of Current Hypertension Reports (journal published by Springer Science Business Media LLC; annual stipend of $5000; editor-in-chief term until December 2022). N.M. Pajewski reports having ownership interest in Eyenovia and Ocuphire Pharma. M.A. Parkulo reports having ownership interest in Apple, Blackberry, Carnival, JPMorgan Chase, Marriott, StitchFix, and Zoom. J. Powell reports receiving research funding from Idorsia (for acting as site PI). F.F. Rahbari-Oskoui reports having consultancy agreements with Astute, Kadmon, Keryx, Phoenix (client Otsuka), Sanofi, and UpToDate; serving in an advisory or leadership role for BMC Nephrology (as associate editor), Journal of Cardiology and Vascular Medicine (as editorial board member), and PKD Foundation; receiving research funding from Duke University, Kadmon, NIH, Otsuka, Reata, and Sanofi/Genzyme; serving on a speakers bureau for Otsuka (unbranded speakers bureau; only raising disease awareness in autosomal dominant polycystic kidney disease without any reference to commercial products); receiving honoraria from Otsuka and Sanofi; and having other interests in, or relationships with, PKD Foundation (scientific advisory board member) and UpToDate (as author, receiving authorship royalties). M. Rahman reports serving as an editorial board member of American Journal of Nephrology and as an associate editor of CJASN; having consultancy agreements with Barologics; receiving research funding from Bayer Pharmaceuticals and Duke Clinical Research Institute; and receiving honoraria from Bayer, Reata, and Relypsa. D.S. Raj reports having other interests in, or relationships with, the American Association of Kidney Patients; serving in an advisory or leadership role for National Heart, Lung, and Blood Institute (NHLBI), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and Novo Nordisk; receiving research funding from the NIH; having consultancy agreements with, and receiving honoraria from, Novo Nordisk. M.V. Rocco reports having consultancy agreements with Bayer, Baxter, and George Clinical; receiving research funding from Bayer, Boehringer Ingelheim, and GlaxoSmithKline; serving as cochair of the ISN Kidney Care Network Project and as chair of NKF Kidney Disease Outcomes Quality Initiative; and serving in an advisory or leadership role for NKF. S. Soman reports serving in an advisory or leadership role for the American Medical Informatics Association, NKF, and NKF of Michigan; having other interests in, or relationships with, American Medical Informatics Association, Cardiorenal Society of America (CRSA), NKF (education committee), and NKF of Michigan (scientific advisory board); being employed by Henry Ford Hospital; and having ownership interest in Nephroceuticals and Pfizer. G. Thomas reports receiving honoraria from UpToDate. All remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

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., (Copyright © 2021 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Importance: COVID-19 vaccines are effective, but inequities in vaccine administration and waning immunity may limit vaccine effectiveness., Objectives: To report statewide trends in vaccine administration and vaccine effectiveness in Minnesota., Design, Setting, and Participants: 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., Exposures: 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., Main Outcomes and Measures: 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., Results: 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., Conclusions and Relevance: 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.

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.

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., (©2021 AMIA - All rights reserved.)

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., Competing Interests: D. Yannopoulos reports receiving research funding from the National Institutes of Health. All remaining authors have nothing to disclose., (Copyright © 2021 by the American Society of Nephrology.)

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 <$165,200; average household income <$35,935; percentage of residents >25 years of age with a bachelor's degree or higher <20.4%), hypertension, and diabetes., Outcomes: CKD (eGFR <60 mL/min/1.73 m 2 , or urinary albumin-creatinine ratio >30mg/g, or urinary protein-creatinine ratio >150mg/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., (Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Rational & Objective: Neighborhood socioeconomic status (SES) and health insurance status may be important upstream social determinants of chronic kidney disease (CKD), but their relationship remains unclear. The aim of this study was to determine whether neighborhood SES and individual-level health insurance status were independently associated with CKD prevalence., Study Design: Observational study using electronic health records (EHRs)., Setting & Participants: EHRs of patients (n = 185,269) seen at a health care system in the 7-county Minneapolis/St Paul area (2017-2018)., Exposures: Census tract neighborhood SES measures (median value of owner-occupied housing units [wealth], percentage of residents aged >25 years with bachelor's degree or higher [education]) and individual-level health insurance status (aged <65 years: Medicaid vs other insurance; ≥65 years: Medicare vs Medicare and supplemental insurance plan) were obtained from the American Community Survey and EHR data. Neighborhood SES was operationalized into quartiles, comparing low (first quartile) versus high (fourth quartile) neighborhood SES., Outcomes: CKD prevalence: estimated glomerular filtration rate < 60 mL/min/1.73 m 2 or proteinuria., Analytic Approach: Multilevel Poisson regression with robust error variance with a random intercept at the census-tract level, adjusted for demographic and clinical covariates, was used to estimate the association between neighborhood SES, insurance, and CKD., Results: Neighborhood SES and insurance were independently associated with CKD prevalence. In covariate-adjusted models, patients living in low versus high neighborhood SES had a higher CKD prevalence among both younger and older patients. For example, the prevalence ratios of CKD in low versus high neighborhood SES as defined by education among patients younger than 65 and 65 years and older were 1.11 (95% CI, 1.05-1.18) and 1.08 (95% CI, 1.04-1.12), respectively. Patients younger than 65 years receiving Medicaid had higher CKD prevalence versus those with other insurance (1.51 [95% CI, 1.43-1.6]). For patients 65 years and older, insurance was not associated with prevalence of CKD in the fully adjusted model., Limitations: One health care system and selection bias., Conclusions: Living in low neighborhood SES as defined by wealth and education and having Medicaid for patients younger than 65 years were associated with higher CKD prevalence., (© 2021 The Authors.)

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 (<120 vs. <140 mm Hg) SBP treatment strategies in adults at increased risk of cardiovascular disease. OH was assessed during follow-up (6, 12, and 24 months) and defined as a decrease in mean seated SBP ≥20 or diastolic BP ≥10 mm Hg after 1 min of standing. WCE, based on 24-hour ambulatory BP monitoring performed at 27 months, was defined as the difference between 27-month seated clinic and daytime ambulatory BP ≥20/≥10 mm Hg. Reverse dipping was defined as a ratio of night-to-daytime SBP >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., (© American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Rational & Objective: Electronic health records can be leveraged to assess quality-of-care measures in patients with chronic kidney disease (CKD). Neighborhood socioeconomic status could be a potential barrier to receiving appropriate evidence-based therapy and follow-up. We examined whether neighborhood socioeconomic status is independently associated with quality of care received by patients with CKD., Study Design: Observational study using electronic health record data., Setting & Participants: Retrospective study of patients seen at a health care system in the 7-county Minneapolis/St Paul area., Exposures: Census tract socioeconomic status measures (wealth, income, and education)., Outcomes: Indicators of CKD quality of care: (1) prescription for angiotensin-converting enzyme inhibitor/angiotensin receptor blocker in patients with stage ≥ 3 CKD or stage 1 or 2 CKD with urinary albumin-creatinine ratio (UACR) > 300 mg/d, (2) UACR measurement among patients with laboratory-based CKD (estimated glomerular filtration rate < 60 mL/min/1.72 m 2 ), and (3) CKD identified on the problem list or coded for at an encounter among patients with laboratory-based CKD., Analytic Approach: Multilevel Poisson regression with robust error variance with a random intercept at the census tract level., Results: Of the 16,776 patients who should be receiving an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, 65% were prescribed these medications. Among patients with laboratory-based CKD (n = 25,097), UACR was measured in 27% and CKD was identified in the electronic health record in 55%. We found no independent association between any neighborhood socioeconomic status measures and CKD quality-of-care indicators., Limitations: 1 health care system and selection bias., Conclusions: We found no association of neighborhood socioeconomic status with quality of CKD care in our cohort. However, adherence to CKD guidelines is low, indicating an opportunity to improve care for all patients regardless of neighborhood socioeconomic status., (© 2021 The Authors.)

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.

Variants in apolipoprotein L1 (APOL1) gene are associated with nondiabetic kidney diseases in black subjects and reduced kidney transplant graft survival. Living and deceased black kidney donors (n = 107) were genotyped for APOL1 variants. To determine whether allografts from high-risk APOL1 donors have reduced podocyte densities contributing to allograft failure, we morphometrically estimated podocyte number, glomerular volume, and podocyte density. We compared allograft loss and eGFR trajectories stratified by APOL1 high-risk and low-risk genotypes. Demographic characteristics were similar in high-risk (n = 16) and low-risk (n = 91) donors. Podocyte density was significantly lower in high-risk than low-risk donors (108 ± 26 vs 127 ± 40 podocytes/10 6 um 3 , P = .03). Kaplan-Meier graft survival (high-risk 61% vs. low-risk 91%, p-value = 0.049) and multivariable Cox models (hazard ratio = 2.6; 95% CI, 0.9-7.8) revealed higher graft loss in recipients of APOL1 high-risk allografts over 48 months. More rapid eGFR decline was seen in recipients of high-risk APOL1 allografts (P < .001). At 60 months, eGFR was 27 vs. 51 mL/min/1.73 min 2 in recipients of APOL1 high-risk vs low-risk kidney allografts, respectively. Kidneys from high-risk APOL1 donors had worse outcomes versus low-risk APOL1 genotypes. Lower podocyte density in kidneys from high-risk APOL1 donors may increase susceptibility to CKD from subsequent stresses in both the recipients and donors., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Importance: There are concerns with translating results from the Systolic Blood Pressure Intervention Trial (SPRINT) into clinical practice because the standardized protocol used to measure blood pressure (BP) may not be consistently applied in routine clinical practice., Objectives: To evaluate the concordance between BPs obtained in routine clinical practice and those obtained using the SPRINT protocol and whether concordance varied by target trial BP., Design, Setting, and Participants: This observational prognostic study linking outpatient vital sign information from electronic health records (EHRs) with data from 49 of the 102 SPRINT sites was conducted from November 8, 2010, to August 20, 2015, among 3074 adults 50 years or older with hypertension without diabetes or a history of stroke. Statistical analysis was performed from May 21, 2019, to March 20, 2020., Main Outcomes and Measures: Blood pressures measured in routine clinical practice and SPRINT., Results: Participant-level EHR data was obtained for 3074 participants (2482 men [80.7%]; mean [SD] age, 68.5 [9.1] years) with 3 or more outpatient and trial BP measurements. In the period from the 6-month study visit to the end of the study intervention, the mean systolic BP (SBP) in the intensive treatment group from outpatient BP recorded in the EHR was 7.3 mm Hg higher (95% CI, 7.0-7.6 mm Hg) than BP measured at trial visits; the mean difference between BP recorded in the outpatient EHR and trial SBP was smaller for participants in the standard treatment group (4.6 mm Hg [95% CI, 4.4-4.9 mm Hg]). Bland-Altman analyses demonstrated low agreement between outpatient BP recorded in the EHR and trial BP, with wide agreement intervals ranging from approximately -30 mm Hg to 45 mm Hg in both treatment groups. In addition, the difference between BP recorded in the EHR and trial BP varied widely by site., Conclusions and Relevance: Outpatient BPs measured in routine clinical practice were generally higher than BP measurements taken in SPRINT, with greater mean SBP differences apparent in the intensive treatment group. There was a consistent high degree of heterogeneity between the BPs recorded in the EHR and trial BPs, with significant variability over time, between and within the participants, and across clinic sites. These results highlight the importance of proper BP measurement technique and an inability to apply 1 common correction factor (ie, approximately 10 mm Hg) to approximate research-quality BP estimates when BP is not measured appropriately in routine clinical practice., Trial Registration: SPRINT ClinicalTrials.gov Identifier: NCT01206062.

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&#95;09&#95;24&#95;JASN2020030236.mp3., (Copyright © 2020 by the American Society of Nephrology.)

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., (© 2020 International Society for Hemodialysis.)

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 <140/90 mm Hg has been reported. However, the prevalence of these phenotypes when targeting an office systolic/diastolic BP goal <120/80 is unknown. The SPRINT (Systolic Blood Pressure Intervention Trial) Ambulatory BP Ancillary study evaluated out-of-office BP using ambulatory BP monitoring in 897 participants 27 months after randomization to intensive versus standard BP targets (office systolic BP <120 versus <140 mm Hg). We used office and daytime BP to assess the proportion of participants with white-coat effect (standard target: office BP ≥140/90 mm Hg and daytime BP <135/85 mm Hg versus intensive target: office BP ≥120/80 mm Hg and daytime BP <120/80 mm Hg) and masked uncontrolled hypertension (standard target: office BP <140/90 mm Hg and daytime BP ≥135/85 mm Hg versus intensive target: office BP <120/80 mm Hg and daytime BP ≥120/80 mm Hg) in each treatment arm. The prevalence of white-coat effect and masked uncontrolled hypertension was 9% and 34%, in both treatment groups. Among participants with uncontrolled office BP, white-coat effect was present in 20% and 23% in the intensive and standard groups, respectively. Among participants with controlled office BP, masked uncontrolled hypertension was present in 62% and 56% in the intensive and standard groups, respectively. In conclusion, a more intensive BP target resulted in a similar proportion of patients with white-coat effect and masked uncontrolled hypertension compared with a standard target.

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: 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 <85, <80, and <75 for participants <65, 65-79, and ≥80 years, respectively; ( 2 ) physical function, measured by the short physical performance battery (SPPB), with higher scores (0-12) indicating better functioning; and ( 3 ) frailty, measured by meeting three or more of the following criteria: slow gait speed, muscle weakness, low physical activity, exhaustion, and unintentional weight loss. Cognitive function and frailty were assessed at the time of ambulatory BP (baseline) and annually thereafter. SPPB was assessed at baseline logistic and linear regression and Cox discrete models assessed the cross-sectional and longitudinal relationship between dipping and BP patterns and outcomes., Results: Mean age of participants was 63±10 years, 56% were male, and 39% were black. At baseline, 129 participants had cognitive impairment, and 275 were frail. Median SPPB score was 9 (interquartile range, 7-10). At baseline, participants with masked hypertension had 0.41 (95% CI, -0.78 to -0.05) lower SPPB scores compared with those with controlled hypertension in the fully adjusted model. Over 4 years of follow-up, 529 participants had incident frailty, and 207 had incident cognitive impairment. After multivariable adjustment, there was no association between BP or dipping patterns and incident frailty or cognitive impairment., Conclusions: In patients with CKD, dipping and BP patterns are not associated with incident or prevalent cognitive impairment or prevalent frailty., (Copyright © 2020 by the American Society of Nephrology.)

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., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

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 <60 mL/min/1.73 m2. 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., (© 2020 S. Karger AG, Basel.)

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., (© American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

African polymorphisms in the gene for Apolipoprotein L1 (APOL1) confer a survival advantage against lethal trypanosomiasis but also an increased risk for several chronic kidney diseases (CKD) including HIV-associated nephropathy (HIVAN). APOL1 is expressed in renal cells, however, the pathogenic events that lead to renal cell damage and kidney disease are not fully understood. The podocyte function of APOL1-G0 versus APOL1-G2 in the setting of a known disease stressor was assessed using transgenic mouse models. Transgene expression, survival, renal pathology and function, and podocyte density were assessed in an intercross of a mouse model of HIVAN (Tg26) with two mouse models that express either APOL1-G0 or APOL1-G2 in podocytes. Mice that expressed HIV genes developed heavy proteinuria and glomerulosclerosis, and had significant losses in podocyte numbers and reductions in podocyte densities. Mice that co-expressed APOL1-G0 and HIV had preserved podocyte numbers and densities, with fewer morphologic manifestations typical of HIVAN pathology. Podocyte losses and pathology in mice co-expressing APOL1-G2 and HIV were not significantly different from mice expressing only HIV. Podocyte hypertrophy, a known compensatory event to stress, was increased in the mice co-expressing HIV and APOL1-G0, but absent in the mice co-expressing HIV and APOL1-G2. Mortality and renal function tests were not significantly different between groups. APOL1-G0 expressed in podocytes may have a protective function against podocyte loss or injury when exposed to an environmental stressor. This was absent with APOL1-G2 expression, suggesting APOL1-G2 may have lost this protective function., Competing Interests: The authors LAB, JRS, JFO and SM have received royalty payments for the commercial use of APOL1 transgenic mice used in this study. This does not alter adherence to PLOS ONE policies on sharing data and materials.

Background Blood pressure ( BP ) varies over time within individual patients and across different BP measurement techniques. The effect of different BP targets on concordance between BP measurements is unknown. The goals of this analysis are to evaluate concordance between (1) clinic and ambulatory BP , (2) clinic visit-to-visit variability and ambulatory BP variability, and (3) first and second ambulatory BP and to evaluate whether different clinic targets affect these relationships. Methods and Results The SPRINT (Systolic Blood Pressure Intervention Trial) ambulatory BP monitoring ancillary study obtained ambulatory BP readings in 897 participants at the 27-month follow-up visit and obtained a second reading in 203 participants 293±84 days afterward. There was considerable lack of agreement between clinic and daytime ambulatory systolic BP with wide limits of agreement in Bland-Altman plots of -21 to 34 mm Hg in the intensive-treatment group and -26 to 32 mm Hg in the standard-treatment group. Overall, there was poor agreement between clinic visit-to-visit variability and ambulatory BP variability with correlation coefficients for systolic and diastolic BP all <0.16. We observed a high correlation between first and second ambulatory BP ; however, the limits of agreement were wide in both the intensive group (-27 to 21 mm Hg) and the standard group (-23 to 20 mm Hg). Conclusions We found low concordance in BP and BP variability between clinic and ambulatory BP and second ambulatory BP . Results did not differ by treatment arm. These results reinforce the need for multiple BP measurements before clinical decision making.

Background: Although hypertension is common in CKD and evidence-based treatment of hypertension has changed considerably, contemporary and nationally representative information about use of angiotensin-converting enzyme (ACEs) inhibitors or angiotensin II receptor blockers (ARBs) in CKD is lacking., Methods: We examined ACE/ARB trends from 1999 to 2014 among 38,885 adult National Health and Nutrition Examination Survey participants with creatinine-based eGFR<60 ml/min per 1.73 m 2 or urinary albumin-to-creatinine ratio ≥30 mg/g., Results: Of 7085 participants with CKD, 34.9% used an ACE/ARB. Across four eras studied, rates of use rose significantly (rates were 25.5% in 1999-2002, 33.3% in 2003-2006, 39.0% in 2007-2010, and 40.1% in 2011-2014) but appeared to plateau after 2003. Among those with CKD, use was significantly greater among non-Hispanic white and black individuals (36.1% and 38.2%, respectively) and lower among Hispanic individuals (26.7%) and other races/ethnicities (29.3%). In age-, sex-, and race/ethnicity-adjusted models, ACE/ARB use was significantly associated with era (adjusted odds ratios [aOR], 1.41; 95% confidence interval [95% CI], 1.14 to 1.74 for 2003-2006, 1.84; 95% CI, 1.48 to 2.28 for 2007-2010, and 2.02; 95% CI, 1.61 to 2.53 for 2011-2014 versus 1999-2002); it also was significantly associated with non-Hispanic black versus non-Hispanic white race/ethnicity (aOR, 1.40; 95% CI, 1.19 to 1.66). Other multivariate associations included older age, men, elevated BMI, diabetes mellitus, treated hypertension, cardiac failure, myocardial infarction, health insurance, and receiving medical care within the prior year., Conclusions: Rates of ACE/ARB use increased in the early 2000s among United States adults with CKD, but for unclear reasons, use appeared to plateau in the ensuing decade. Research examining barriers to care and other factors is needed., (Copyright © 2019 by the American Society of Nephrology.)

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 <30 mL/min/1.73 m2) were examined using Cox proportional hazards models., Results: Among 384 869 eligible patients, 51% had at least one Cr measured during the exposure period. Outpatient AKI occurred in 1.4% of patients while hospital AKI occurred in only 0.3% of patients. The average follow-up was 5.3 years. Outpatient AKI was associated with an increased risk of all-cause mortality {adjusted hazard ratio [aHR] 1.90 [95% confidence interval (CI) 1.76-2.06]} and results were consistent across all AKI groups. Outpatient AKI was also associated with an increased risk of renal events [aHR 1.33 (95% CI 1.11-1.59)], even among those who recovered., Conclusions: Outpatient AKI is more prevalent than inpatient AKI and is a risk factor for all-cause mortality and renal events, even among those who recover kidney function. Further research is necessary to determine risk factors and identify strategies for preventing outpatient AKI., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

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., (Copyright © 2019 American College of Cardiology Foundation. All rights reserved.)