Publications by authors named "Alan S Go"

467 Publications

Human immunodeficiency virus infection and risks of morbidity and death in adults with incident heart failure.

Eur Heart J Open 2021 Nov 1;1(3):oeab040. Epub 2021 Dec 1.

Division of Research, Kaiser Permanente Northern California, 2000 Broadway, Oakland, CA 94612, USA.

Aims: Human immunodeficiency virus (HIV) increases the risk of heart failure (HF), but whether it influences subsequent morbidity and mortality remains unclear.

Methods And Results: We investigated the risks of hospitalization for HF, HF-related emergency department (ED) visits, and all-cause death in an observational cohort of incident HF patients with and without HIV using data from three large US integrated healthcare delivery systems. We estimated incidence rates and adjusted hazard ratios (aHRs) by HIV status at the time of HF diagnosis for subsequent outcomes. We identified 448 persons living with HIV (PLWH) and 3429 without HIV who developed HF from a frequency-matched source cohort of 38 868 PLWH and 386 586 without HIV. Mean age was 59.5 ± 11.3 years with 9.8% women and 31.8% Black, 13.1% Hispanic, and 2.2% Asian/Pacific Islander. Compared with persons without HIV, PLWH had similar adjusted rates of HF hospitalization [aHR 1.01, 95% confidence interval (CI): 0.81-1.26] and of HF-related ED visits [aHR 1.22 (95% CI: 0.99-1.50)], but higher adjusted rates of all-cause death [aHR 1.31 (95% CI: 1.08-1.58)]. Adjusted rates of HF-related morbidity and all-cause death were directionally consistent across a wide range of CD4 counts but most pronounced in the subset with a baseline CD4 count <200 or 200-499 cells/μL.

Conclusion: In a large, diverse cohort of adults with incident HF receiving care within integrated healthcare delivery systems, PLWH were at an independently higher risk of all-cause death but not HF hospitalizations or HF-related ED visits. Future studies investigating modifiable HIV-specific risk factors may facilitate more personalized care to optimize outcomes for PLWH and HF.
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http://dx.doi.org/10.1093/ehjopen/oeab040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9242035PMC
November 2021

Considerations in Controlling for Urine Concentration for Biomarkers of Kidney Disease Progression After Acute Kidney Injury.

Kidney Int Rep 2022 Jul 6;7(7):1502-1513. Epub 2022 Apr 6.

Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Introduction: Biomarkers of acute kidney injury (AKI) are often indexed to urine creatinine (UCr) or urine osmolarity (UOsm) to control for urine concentration. We evaluated how these approaches affect the biomarker-outcome association in patients with AKI.

Methods: The Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury Study was a cohort of hospitalized patients with and without AKI between 2009 and 2015. Using Cox proportional hazards regression, we assessed the associations and predictions (C-statistics) of urine biomarkers with a composite outcome of incident chronic kidney disease (CKD) and CKD progression. We used 4 approaches to account for urine concentration: indexing and adjusting for UCr and UOsm.

Results: Among 1538 participants, 769 (50%) had AKI and 300 (19.5%) developed composite CKD outcome at median follow-up of 4.7 years. UCr and UOsm during hospitalization were inversely associated with the composite CKD outcome. The associations and predictions with CKD were significantly strengthened after indexing or adjusting for UCr or UOsm for urine kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), and monocyte chemoattractant protein-1 (MCP-1) in patients with AKI. There was no significant improvement with indexing or adjusting UCr or UOsm for albumin, neutrophil gelatinase-associated lipocalin (NGAL), and chitinase 3-like 1 (YKL-40). Uromodulin's (UMOD) inverse association with the outcome was significantly blunted after indexing but not adjusting for UCr or UOsm.

Conclusion: UCr and UOsm during hospitalization are inversely associated with development and progression of CKD. Indexing or adjusting for UCr or UOsm strengthened associations and improved predictions for CKD for only some biomarkers. Incorporating urinary concentration should be individualized for each biomarker in research and clinical applications.
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http://dx.doi.org/10.1016/j.ekir.2022.03.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263319PMC
July 2022

Analysis of Worsening Heart Failure Events in an Integrated Health Care System.

J Am Coll Cardiol 2022 Jul;80(2):111-122

Division of Research, Kaiser Permanente Northern California, Oakland, California, USA; Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, California, USA; Departments of Epidemiology, Biostatistics and Medicine, University of California-San Francisco, San Francisco, California, USA; Department of Medicine, Stanford University, Palo Alto, California, USA.

Background: There is growing interest to disentangle worsening heart failure (WHF) from location of care and move away from hospitalization as a surrogate for acuity.

Objectives: The purpose of this study was to describe the incidence of WHF events across the care continuum from ambulatory encounters to hospitalizations.

Methods: We studied calendar year cohorts of adults with diagnosed heart failure (HF) from 2010-2019 within a large, integrated health care delivery system. Electronic health record (EHR) data were accessed for outpatient encounters, emergency department (ED) visits/observation stays, and hospitalizations. WHF was defined as ≥1 symptom, ≥2 objective findings including ≥1 sign, and ≥1 change in HF-related therapy. Symptoms and signs were ascertained using natural language processing.

Results: We identified 103,138 eligible individuals with mean age 73.6 ± 13.7 years, 47.5% women, and mean left ventricular ejection fraction of 51.4% ± 13.7%. There were 1,136,750 unique encounters including 743,039 (65.4%) outpatient encounters, 224,670 (19.8%) ED visits/observation stays, and 169,041 (14.9%) hospitalizations. A total of 126,008 WHF episodes were identified, including 34,758 (27.6%) outpatient encounters, 28,301 (22.5%) ED visits/observation stays, and 62,949 (50.0%) hospitalizations. The annual incidence (events per 100 person-years) of WHF increased from 25 to 33 during the study period primarily caused by outpatient encounters (7 to 10) and ED visits/observation stays (4 to 7). The 30-day rate of hospitalizations for WHF ranged from 8.2% for outpatient encounters to 12.4% for hospitalizations.

Conclusions: ED visits/observation stays and outpatient encounters account for approximately one-half of WHF events, are driving the underlying growth in HF morbidity, and portend a poor short-term prognosis.
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http://dx.doi.org/10.1016/j.jacc.2022.04.045DOI Listing
July 2022

Health-related quality of life associated with warfarin and direct oral anticoagulants in venous thromboembolism.

Thromb Res 2022 Aug 28;216:97-102. Epub 2022 Jun 28.

Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, CA, USA; Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA.

Introduction: Venous thromboembolism (VTE) is commonly treated with oral anticoagulants, including warfarin or direct oral anticoagulants (DOACs). Although DOACs are associated with favorable treatment satisfaction, few studies have assessed whether quality of life differs between DOAC and warfarin users.

Materials And Methods: We invited adults enrolled in two California-based integrated health care delivery systems and with a history of VTE between January 1, 2015 and June 30, 2018 to complete a survey on their experience with anticoagulants. Health-related quality of life (QOL) was assessed using the RAND 36-item Short Form Health Survey (SF-36), which measures QOL in 2 general component scores (physical and mental). We used multivariable linear regression to compare mean QOL component scores between DOAC-users and warfarin-users, adjusting for patient and clinical characteristics.

Results: Overall, 2230 patients (43.1 % women and 31.8 % >75 years of age) taking anticoagulants answered at least 1 question on the SF-36, 975 taking DOACs and 1255 taking warfarin. After adjustment for patient-level factors, there were no significant differences in either physical component scores (39.2 v 38.3, p = 0.24) or mental component scores (48.5 v 49.0, p = 0.42) between DOAC and warfarin users.

Conclusions: Health-related QOL did not significantly differ between DOAC and warfarin users with a history of VTE.
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http://dx.doi.org/10.1016/j.thromres.2022.06.008DOI Listing
August 2022

Association of Estimated GFR Calculated Using Race-Free Equations With Kidney Failure and Mortality by Black vs Non-Black Race.

JAMA 2022 06;327(23):2306-2316

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health and the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, Maryland.

Importance: At a given estimated glomerular filtration rate (eGFR), individuals who are Black have higher rates of mortality and kidney failure with replacement therapy (KFRT) compared with those who are non-Black. Whether the recently adopted eGFR equations without race preserve racial differences in risk of mortality and KFRT at a given eGFR is unknown.

Objective: To assess whether eGFR equations with and without race and cystatin C document racial differences in risk of KFRT and mortality in populations including Black and non-Black participants.

Design, Setting, And Participants: Retrospective individual-level data analysis of 62 011 participants from 5 general population and 3 chronic kidney disease (CKD) US-based cohorts with serum creatinine, cystatin C, and follow-up for KFRT and mortality from 1988 to 2018.

Exposures: Chronic Kidney Disease Epidemiology Collaboration equation with serum creatinine (eGFRcr with and without race), cystatin C (eGFRcys without race), or both markers (eGFRcr-cys without race).

Main Outcomes And Measures: The prevalence of decreased eGFR at baseline and hazard ratios of KFRT and mortality in Black vs non-Black participants were calculated, adjusted for age and sex. Analyses were performed within each cohort and with random-effect meta-analyses of the models.

Results: Among 62 011 participants (20 773 Black and 41 238 non-Black; mean age, 63 years; 53% women), the prevalence ratio (95% CI; percent prevalences) of eGFR less than 60 mL/min/1.73 m2 comparing Black with non-Black participants was 0.98 (95% CI, 0.93-1.03; 11% vs 12%) for eGFRcr with race, 0.95 (95% CI, 0.91-0.98; 17% vs 18%) for eGFRcys, and 1.2 (95% CI, 1.2-1.3; 13% vs 11%) for eGFRcr-cys but was 1.8 (95% CI, 1.7-1.8; 15% vs 9%) for eGFRcr without race. During a mean follow-up of 13 years, 8% and 4% of Black and non-Black participants experienced KFRT and 34% and 39% died, respectively. Decreased eGFR was associated with significantly greater risk of both outcomes for all equations. At an eGFR of 60 mL/min/1.73 m2, the hazard ratios for KFRT comparing Black with non-Black participants were 2.8 (95% CI, 1.6-4.9) for eGFRcr with race, 3.0 (95% CI, 1.5-5.8) for eGFRcys, and 2.8 (95% CI, 1.4-5.4) for eGFRcr-cys vs 1.3 (95% CI, 0.8-2.1) for eGFRcr without race. The 5-year absolute risk differences for KFRT comparing Black with non-Black participants were 1.4% (95% CI, 0.2%-2.6%) for eGFRcr with race, 1.1% (95% CI, 0.2%-1.9%) for eGFRcys, and 1.3% (95% CI, 0%-2.6%) for eGFRcr-cys vs 0.37% (95% CI, -0.32% to 1.05%) for eGFRcr without race. Similar patterns were observed for mortality.

Conclusions And Relevance: In this retrospective analysis of 8 US cohorts including Black and non-Black individuals, the eGFR equation without race that included creatinine and cystatin C, but not the eGFR equation without race that included creatinine without cystatin C, demonstrated racial differences in the risk of KFRT and mortality throughout the range of eGFR. The eGFRcr-cys equation may be preferable to the eGFRcr equation without race for assessing racial differences in the risk of KFRT and mortality associated with low eGFR.
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http://dx.doi.org/10.1001/jama.2022.8801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171658PMC
June 2022

Effect of Lifestyle Coaching or Enhanced Pharmacotherapy on Blood Pressure Control Among Black Adults With Persistent Uncontrolled Hypertension: A Cluster Randomized Clinical Trial.

JAMA Netw Open 2022 05 2;5(5):e2212397. Epub 2022 May 2.

Division of Research, Kaiser Permanente Northern California, Oakland.

Importance: Greater difficulty in controlling blood pressure (BP) and adverse lifestyle practices such as higher salt intake or less physical activity may account for some of the differences between BP control rates in Black vs White adults, thereby exposing Black adults to a higher risk of vascular events.

Objective: To determine whether a lifestyle coaching intervention or an enhanced pharmacotherapy protocol is more effective than usual care in improving BP control rates in Black adults treated within an integrated health care delivery system.

Design, Setting, And Participants: Shake, Rattle & Roll, a cluster randomized clinical trial, was conducted from June 5, 2013, to June 11, 2018, in a large integrated health care delivery system. Enrollment was completed during a 12-month period and interventions were implemented for 12 months. Follow-up lasted 48 months after enrollment. Panels of Black adult members of the health care delivery system with BP of at least 140/90 mm Hg from 98 adult primary care physicians were randomly assigned at the primary care physician level to usual care (UC group [n = 1129]), enhanced pharmacotherapy monitoring (EP group [n = 346]) of current BP management protocol, or diet and lifestyle coaching consisting of photographs, stories, and recipes, for example, that are appropriate for Black adults (LC group [n = 286]) focused on the Dietary Approaches to Stop Hypertension (DASH) diet. Data were analyzed from June 1, 2016, to March 25, 2022.

Interventions: The UC group received care per customary protocol. The EP group was contacted by a research nurse and/or a clinical pharmacist to discuss barriers to hypertension control, and drug therapy emphasized the use of thiazide diuretic intensification and addition of spironolactone as needed. The LC group received as many as 16 telephone sessions with a lifestyle coach and an emphasis on implementing reduction of sodium intake and the DASH diet.

Main Outcomes And Measures: Intention-to-treat analysis of BP control rates at end of the 12-month intervention.

Results: Among the 1761 participants, the mean (SD) age was 61 (13) years, and 1214 (68.9%) were women. At the end of the 12-month intervention period, there was no significant difference in BP control rate among study groups (UC, 61.8% [95% CI, 58.8%-64.9%]; EP, 64.5% [95% CI, 59.0%-69.4%]; LC, 67.8% [95% CI, 62.1%-73.2%]; LC vs EP, P = .07). However, greater BP control was present in the LC group vs UC at 24 months (UC, 61.2% [95% CI, 57.3%-64.7%]; EP, 67.6% [95% CI, 61.9%-72.8%]; LC, 72.4% [95% CI, 66.9%-78.1%]; LC vs UC, P = .001), and 48 months (UC, 64.5% [95% CI, 61.6%-67.2%]; EP, 66.5% [95% CI, 61.3%-71.3%]; LC, 73.1% [95% CI, 67.6%-77.9%]; LC vs UC, P = .006) after enrollment. The contribution of BP medication adherence to explain group differences was inconclusive.

Conclusions And Relevance: In this cluster randomized clinical trial including Black adults with persistent uncontrolled hypertension, a 12-month LC intervention was more effective at controlling BP than UC at 24 and 48 months after enrollment. Further research is needed to explore the potential implementation of this intervention into clinical practice.

Trial Registration: ClinicalTrials.gov Identifier: NCT01892592.
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http://dx.doi.org/10.1001/jamanetworkopen.2022.12397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9118047PMC
May 2022

Multimorbidity Burden and Incident Heart Failure Among People With and Without HIV: The HIV-HEART Study.

Mayo Clin Proc Innov Qual Outcomes 2022 Jun 3;6(3):218-227. Epub 2022 May 3.

Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA.

Objective: To examine the association between multimorbidity burden and incident heart failure (HF) among people with HIV (PWH) and people without HIV (PWoH).

Patients And Methods: The HIV-HEART study is a retrospective cohort study that included adult PWH and PWoH aged 21 years or older at Kaiser Permanente between 2000 and 2016. Multimorbidity burden was defined by the baseline prevalence of 22 chronic conditions and was categorized as 0-1, 2-3, and 4 or more comorbidities on the basis of distribution of the overall population. People with HIV and PWoH were followed for a first HF event, all-cause death, or up to the end of follow-up on December 31, 2016. Using Cox proportional hazard regression, hazard ratios and 95% CIs were calculated to examine the association between multimorbidity burden and incident HF among PWH and PWoH, separately.

Results: The prevalences of 0-1, 2-3, and 4 or more comorbidities were 83.3%, 13.0%, and 3.7% in PWH (n=38,868), and 82.2%, 14.3%, and 3.5% in PWoH (n=386,586), respectively. After multivariable adjustment, compared with people with 0-1 comorbidities, the hazard ratios of incident HF associated with 2-3 and 4 or more comorbidities were 1.33 (95% CI, 1.04-1.71) and 2.41 (95% CI, 1.78-3.25) in PWH and 2.10 (95% CI, 1.92-2.29) and 4.09 (95% CI, 3.64-4.61) in PWoH, respectively.

Conclusion: Multimorbidity was associated with a higher risk of incident HF among PWH and PWoH, with more prominent associations in PWoH and certain patient subgroups. The identification of specific multimorbidity patterns that contribute to higher HF risk in PWH may lead to future preventative strategies.
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http://dx.doi.org/10.1016/j.mayocpiqo.2022.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9079699PMC
June 2022

ReducinG stroke by screening for UndiAgnosed atRial fibrillation in elderly inDividuals (GUARD-AF): Rationale and design of the GUARD-AF randomized trial of screening for atrial fibrillation with a 14-day patch-based continuous ECG monitor.

Am Heart J 2022 07 25;249:76-85. Epub 2022 Apr 25.

Bristol Myers Squibb, Inc., NJ.

Background: Screening for atrial fibrillation (AF) is attractive because AF independently raises the risk of ischemic stroke, this risk is largely reversible by long-term oral anticoagulant therapy (OAC), and many patients with AF remain undiagnosed and untreated. Recent trials of one-time brief screening for AF have not produced a significant increase in the proportion of patients diagnosed with AF. Trials of longer-term screening have demonstrated an increase in AF diagnoses, primarily paroxysmal AF. To date, however, no trials have demonstrated that screening for AF results in lower rates of stroke. Clinical practice guidelines conflict in their level of support for screening for AF.

Methods: The GUARD-AF individually randomized trial is designed to test whether screening for AF in individuals age 70 years or greater using a 2-week single-lead electrocardiographic patch monitor can identify patients with undiagnosed AF and lead to treatment with OAC, resulting in a reduced rate of stroke in the screened population. The trial's efficacy end point is hospitalization for stroke (either ischemic or hemorrhagic) and the trial's safety end point is hospitalization for a bleeding event. End points will be ascertained via Medicare claims or electronic health records at 2.5 years after study start. Enrollment is based in primary care practices and the OAC decision for screen-detected cases is left to the patient and their physician. The initial planned target sample size was 52,000, with 26,000 allocated to either screening or to usual care.

Results: Trial enrollment was severely hampered by the novel coronavirus disease 2019 (COVID-19) pandemic and stopped at a total enrollment of 11,931 participants. Of 5,965 randomized to the screening arm, 5,713 patients (96%) returned monitors with analyzable results. Incidence of screen-detected and clinically detected AF and associated stroke and bleeding outcomes will be ascertained.

Conclusions: GUARD-AF is the largest AF screening randomized trial using a longer-term patch-based continuous electrocardiographic monitor. The results will contribute important information on the yield of patch-based AF screening, the "burden" of AF detected (percent time in AF, longest episode), and physicians' OAC decisions as a function of AF burden. GUARD-AF's stroke and bleed results will contribute to pooled trial analyses of AF screening, thereby informing future studies and guidelines.
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http://dx.doi.org/10.1016/j.ahj.2022.04.005DOI Listing
July 2022

Prognostic Accuracy of Presepsis and Intrasepsis Characteristics for Prediction of Cardiovascular Events After a Sepsis Hospitalization.

Crit Care Explor 2022 Apr 8;4(4):e0674. Epub 2022 Apr 8.

The Permanente Medical Group, Oakland, CA.

Objectives: Sepsis survivors face increased risk for cardiovascular complications; however, the contribution of intrasepsis events to cardiovascular risk profiles is unclear.

Setting: Kaiser Permanente Northern California (KPNC) and Intermountain Healthcare (IH) integrated healthcare delivery systems.

Subjects: Sepsis survivors (2011-2017 [KPNC] and 2018-2020 [IH]) greater than or equal to 40 years old without prior cardiovascular disease.

Design: Data across KPNC and IH were harmonized and grouped into presepsis (demographics, atherosclerotic cardiovascular disease scores, comorbidities) or intrasepsis factors (e.g., laboratory values, vital signs, organ support, infection source) with random split for training/internal validation datasets (75%/25%) within KPNC and IH. Models were bidirectionally, externally validated between healthcare systems.

Interventions: None.

Measurements And Main Results: Changes to predictive accuracy (-statistic) of cause-specific proportional hazards models predicting 1-year cardiovascular outcomes (atherosclerotic cardiovascular disease, heart failure, and atrial fibrillation events) were compared between models that did and did not contain intrasepsis factors. Among 39,590 KPNC and 16,388 IH sepsis survivors, 3,503 (8.8%) at Kaiser Permanente (KP) and 600 (3.7%) at IH experienced a cardiovascular event within 1-year after hospital discharge, including 996 (2.5%) at KP and 192 (1.2%) IH with an atherosclerotic event first, 564 (1.4%) at KP and 117 (0.7%) IH with a heart failure event, 2,310 (5.8%) at KP and 371 (2.3%) with an atrial fibrillation event. Death within 1 year after sepsis occurred for 7,948 (20%) KP and 2,085 (12.7%) IH patients. Combined models with presepsis and intrasepsis factors had better discrimination for cardiovascular events (KPNC -statistic 0.783 [95% CI, 0.766-0.799]; IH 0.763 [0.726-0.801]) as compared with presepsis cardiovascular risk alone (KPNC: 0.666 [0.648-0.683], IH 0.660 [0.619-0.702]) during internal validation. External validation of models across healthcare systems showed similar performance (KPNC model within IH data -statistic: 0.734 [0.725-0.744]; IH model within KPNC data: 0.787 [0.768-0.805]).

Conclusions: Across two large healthcare systems, intrasepsis factors improved postsepsis cardiovascular risk prediction as compared with presepsis cardiovascular risk profiles. Further exploration of sepsis factors that contribute to postsepsis cardiovascular events is warranted for improved mechanistic and predictive models.
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http://dx.doi.org/10.1097/CCE.0000000000000674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000037PMC
April 2022

Black and White Adults With CKD Hospitalized With Acute Kidney Injury: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

Am J Kidney Dis 2022 Apr 8. Epub 2022 Apr 8.

Division of Nephrology, Department of Medicine, University of California, San Francisco, California; Division of Research, Kaiser Permanente Northern California, Oakland, California.

Rationale & Objective: Few studies have investigated racial disparities in acute kidney injury (AKI), in contrast to the extensive literature on racial differences in the risk of kidney failure. We sought to study potential differences in risk in the setting of chronic kidney disease (CKD).

Study Design: Prospective cohort study.

Setting & Participants: We studied 2,720 self-identified Black or White participants with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study from July 1, 2013, to December 31, 2017.

Exposure: Self-reported race (Black vs White).

Outcome: Hospitalized AKI (≥50% increase from nadir to peak serum creatinine).

Analytical Approach: Cox regression models adjusting for demographics (age and sex), prehospitalization clinical risk factors (diabetes, blood pressure, cardiovascular disease, estimated glomerular filtration rate, proteinuria, receipt of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers), and socioeconomic status (insurance status and education level). In a subset of participants with genotype data, we adjusted for apolipoprotein L1 gene (APOL1) high-risk status and sickle cell trait.

Results: Black participants (n = 1,266) were younger but had a higher burden of prehospitalization clinical risk factors. The incidence rate of first AKI hospitalization among Black participants was 6.3 (95% CI, 5.5-7.2) per 100 person-years versus 5.3 (95% CI, 4.6-6.1) per 100 person-years among White participants. In an unadjusted Cox regression model, Black participants were at a modestly increased risk of incident AKI (HR, 1.22 [95% CI, 1.01-1.48]) compared with White participants. However, this risk was attenuated and no longer significant after adjusting for prehospitalization clinical risk factors (adjusted HR, 1.02 [95% CI, 0.83-1.25]). There were only 11 AKI hospitalizations among individuals with high-risk APOL1 risk status and 14 AKI hospitalizations among individuals with sickle cell trait.

Limitations: Participants were limited to research volunteers and potentially not fully representative of all CKD patients.

Conclusions: In this multicenter prospective cohort of CKD patients, racial disparities in AKI incidence were modest and were explained by differences in prehospitalization clinical risk factors.
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http://dx.doi.org/10.1053/j.ajkd.2022.02.021DOI Listing
April 2022

Acute Kidney Injury Associates with Long-Term Increases in Plasma TNFR1, TNFR2, and KIM-1: Findings from the CRIC Study.

J Am Soc Nephrol 2022 06 16;33(6):1173-1181. Epub 2022 Mar 16.

Division of Nephrology, University of Michigan, Ann Arbor, Michigan.

Background: Some markers of inflammation-TNF receptors 1 and 2 (TNFR1 and TNFR2)-are independently associated with progressive CKD, as is a marker of proximal tubule injury, kidney injury molecule 1 (KIM-1). However, whether an episode of hospitalized AKI may cause long-term changes in these biomarkers is unknown.

Methods: Among adult participants in the Chronic Renal Insufficiency Cohort (CRIC) study, we identified 198 episodes of hospitalized AKI (defined as peak/nadir inpatient serum creatinine values ≥1.5). For each AKI hospitalization, we found the best matched non-AKI hospitalization (unique patients), using prehospitalization characteristics, including eGFR and urine protein/creatinine ratio. We measured TNFR1, TNFR2, and KIM-1 in banked plasma samples collected at annual CRIC study visits before and after the hospitalization (a median of 7 months before and 5 months after hospitalization).

Results: In the AKI and non-AKI groups, we found similar prehospitalization median levels of TNFR1 (1373 pg/ml versus 1371 pg/ml, for AKI and non-AKI, respectively), TNFR2 (47,141 pg/ml versus 46,135 pg/ml, respectively), and KIM-1 (857 pg/ml versus 719 pg/ml, respectively). Compared with matched study participants who did not experience AKI, study participants who did experience AKI had greater increases in TNFR1 (23% versus 10%, <0.01), TNFR2 (10% versus 3%, <0.01), and KIM-1 (13% versus -2%, <0.01).

Conclusions: Among patients with CKD, AKI during hospitalization was associated with increases in plasma TNFR1, TNFR2, and KIM-1 several months after their hospitalization. These results highlight a potential mechanism by which AKI may contribute to more rapid loss of kidney function months to years after the acute insult.
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http://dx.doi.org/10.1681/ASN.2021111453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9161789PMC
June 2022

Prognostic value of echocardiography for heart failure and death in adults with chronic kidney disease.

Am Heart J 2022 06 10;248:84-96. Epub 2022 Mar 10.

Division of Research, Kaiser Permanente Northern California, Oakland, CA USA; Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, CA USA; Departments of Epidemiology, Biostatistics and Medicine, University of California, San Francisco, CA USA; Department of Medicine, Stanford University, Palo Alto, CA USA.

Background: Adults with chronic kidney disease (CKD) are at increased risk of heart failure (HF) morbidity and mortality. Despite well-characterized abnormalities in cardiac structure in CKD, it remains unclear how to optimally leverage echocardiography to risk stratify CKD patients.

Methods: We evaluated associations between echocardiographic parameters and risk of HF hospitalization and death using Cox proportional hazard models and forward selection with integrated discrimination improvement (IDI).

Results: The study included 3,505 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study. Mean age was 59 ± 11 years, HF prevalence was 10%, and mean left ventricular (LV) ejection fraction (LVEF) was 54 ± 9%. During median 11 (interquartile range: 8-12) years of follow-up, event rates per 100-person years for HF hospitalizations and death, respectively, were 9.4 (95% Confidence Interval [CI]: 7.9-11.3) and 8.9 (95% CI: 7.6-10.5) for participants with LVEF <40%, 3.5 (95% CI: 3.0-4.2) and 4.6 (95% CI: 4.0-5.2) for patients with LVEF 40% to 49%, and 1.9 (95% CI: 1.7-2.1) and 3.1 (95% CI: 2.9-3.3) for patients with LVEF >50%. The rate of HF hospitalizations and deaths increased with lower eGFR across all LVEF categories. LV mass index, LVEF, and LV geometry had the strongest association with outcomes but provided modest incremental prognostic value to a baseline clinical model (IDI = 0.14 and ΔAUC = 0.017 for HF hospitalization, IDI = 0.12 and ΔAUC = 0.008 for death).

Conclusions: Baseline echocardiographic parameters are independently associated with increased risk of subsequent HF morbidity and mortality but provide only marginal incremental prognostic utility beyond clinical characteristics in the setting of CKD.
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http://dx.doi.org/10.1016/j.ahj.2022.02.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9064944PMC
June 2022

Large-scale identification of aortic stenosis and its severity using natural language processing on electronic health records.

Cardiovasc Digit Health J 2021 Jun 18;2(3):156-163. Epub 2021 Mar 18.

Division of Research, Kaiser Permanente Northern California, Oakland, California.

Background: Systematic case identification is critical to improving population health, but widely used diagnosis code-based approaches for conditions like valvular heart disease are inaccurate and lack specificity.

Objective: To develop and validate natural language processing (NLP) algorithms to identify aortic stenosis (AS) cases and associated parameters from semi-structured echocardiogram reports and compare their accuracy to administrative diagnosis codes.

Methods: Using 1003 physician-adjudicated echocardiogram reports from Kaiser Permanente Northern California, a large, integrated healthcare system (>4.5 million members), NLP algorithms were developed and validated to achieve positive and negative predictive values > 95% for identifying AS and associated echocardiographic parameters. Final NLP algorithms were applied to all adult echocardiography reports performed between 2008 and 2018 and compared to ICD-9/10 diagnosis code-based definitions for AS found from 14 days before to 6 months after the procedure date.

Results: A total of 927,884 eligible echocardiograms were identified during the study period among 519,967 patients. Application of the final NLP algorithm classified 104,090 (11.2%) echocardiograms with any AS (mean age 75.2 years, 52% women), with only 67,297 (64.6%) having a diagnosis code for AS between 14 days before and up to 6 months after the associated echocardiogram. Among those without associated diagnosis codes, 19% of patients had hemodynamically significant AS (ie, greater than mild disease).

Conclusion: A validated NLP algorithm applied to a systemwide echocardiography database was substantially more accurate than diagnosis codes for identifying AS. Leveraging machine learning-based approaches on unstructured electronic health record data can facilitate more effective individual and population management than using administrative data alone.
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http://dx.doi.org/10.1016/j.cvdhj.2021.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8890044PMC
June 2021

Global assessment improves risk stratification for major adverse cardiac events across a wide range of triglyceride levels: Insights from the KP REACH study.

Am J Prev Cardiol 2022 Mar 29;9:100319. Epub 2022 Jan 29.

Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.

Objective: Patients with risk factors for or established atherosclerotic cardiovascular disease (ASCVD) remain at high risk for subsequent ischemic events despite statin therapy. Triglyceride (TG) levels may contribute to residual ASCVD risk, and the performance of global risk assessment calculators across a broad range of TG levels is unknown.

Methods: We performed a retrospective cohort study of Kaiser Permanente Northern California members aged ≥45 years with ≥1 ASCVD risk factor (primary prevention cohort) or established ASCVD (secondary prevention cohort) between 2010 and 2017 who were receiving statin therapy and had a low-density lipoprotein cholesterol between 41-100 mg/dL. Global ASCVD risk assessment was performed using both the Kaiser Permanente ASCVD Risk Estimator (KPARE) and the ACC/AHA ASCVD Pooled Cohort Equation (PCE). Outcomes included major adverse cardiovascular events (MACE) defined as myocardial infarction, stroke, or peripheral artery disease, and expanded MACE (MACE + coronary revascularization + hospitalization for unstable angina).

Results: Among 373,389 patients in the primary prevention cohort, median TG was 122 mg/dL (IQR 88-172 mg/dL) and there were 0.2 MACE events and 0.3 expanded MACE events per 100-person years. Among 97,832 patients in the secondary prevention cohort, median TG level was 116 mg/dL (IQR 84-164 mg/dL) and there were 9.6 MACE events and 22.0 expanded MACE events per 100-person years. KPARE and the ACC/AHA PCE stratified patients for MACE and expanded MACE over the entire range of TGs.

Conclusion: In a cohort receiving statin therapy for primary or secondary prevention, we found global assessment further improves risk stratification for initial and/or recurrent ASCVD events irrespective of baseline TG level.
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http://dx.doi.org/10.1016/j.ajpc.2022.100319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8844399PMC
March 2022

Food security, diet quality, nutritional knowledge, and attitudes towards research in adults with heart failure during the COVID-19 pandemic.

Clin Cardiol 2022 Feb 2;45(2):180-188. Epub 2022 Feb 2.

Department of Cardiology, Kaiser Permanente San Francisco Medical Center, San Francisco, California, USA.

Background: The impact of the novel coronavirus disease 2019 (COVID-19) pandemic on diet and nutrition among older adults with chronic medical conditions have not been well-described.

Methods: We conducted a survey addressing (1) food access, (2) diet quality and composition, (3) nutritional understanding, and (4) attitudes towards research among adults with heart failure (HF) within an integrated health system. Adults (≥18 years) with diagnosed HF and at least one prior hospitalization for HF within the last 12 months were approached to complete the survey electronically or by mail. Outcomes included all-cause and HF-specific hospitalizations and all-cause death was ascertained via the electronic health record.

Results: Among 1212 survey respondents (32.5% of eligible patients) between May 18, 2020 and September 30, 2020, mean ± SD age was 77.9 ± 11.4 years, 50.1% were women, and median (25th-75th) left ventricular ejection fraction was 55% (40%-60%). Overall, 15.1% of respondents were food insecure, and only 65% of participants answered correctly more than half of the items assessing nutritional knowledge. Although most respondents were willing to participate in future research, that number largely declined for studies requiring blood draws (32.2%), study medication (14.4%), and/or behavior change (27.1%). Food security, diet quality, and nutritional knowledge were not independently associated with outcomes at 90 or 180 days.

Conclusion: In a cohort of older adults with HF and multiple comorbidities, a significant proportion reported issues with food access, diet quality, and nutritional knowledge during the COVID-19 pandemic. Future research should evaluate interventions targeting these domains in at-risk individuals.
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http://dx.doi.org/10.1002/clc.23761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8860486PMC
February 2022

Loop and thiazide diuretic use and risk of chronic kidney disease progression: a multicentre observational cohort study.

BMJ Open 2022 01 31;12(1):e048755. Epub 2022 Jan 31.

Division of Research, Kaiser Permanente Northern California, Oakland, California, USA

Objectives: To evaluate the association between diuretic use by class with chronic kidney disease (CKD) progression and onset of end-stage renal disease (ESRD).

Design: Retrospective cohort study.

Setting: Large integrated healthcare delivery system in Northern California.

Participants: Adults with an estimated glomerular filtration rate (eGFR) 15-59 min/1.73 m by the CKD-Epidemiology Collaboration equation with no prior diuretic use.

Main Outcome Measures: ESRD and a renal composite outcome including eGFR <15 mL/min/1.73 m, 50% reduction in eGFR and/or ESRD.

Results: Among 47 666 eligible adults with eGFR 15-59 min/1.73 m and no previous receipt of loop or thiazide diuretics, mean age was 71 years, 49% were women and 26% were persons of colour. Overall, the rate (per 100 person-years) of the renal composite outcome was 1.35 (95% CI: 1.30 to 1.41) and 0.42 (95% CI: 0.39 to 0.45) for ESRD. Crude rates (per 100 person-years) of the composite renal outcome were higher in patients who initiated loop diuretics (12.85 (95% CI: 11.81 to 13.98) vs 1.06 (95% CI: 1.02 to 1.12)) and thiazide diuretics (2.68 (95% CI: 2.33 to 3.08) vs 1.29 (95% CI: 1.24 to 1.35)) compared with those who did not. Crude rates (per 100-person years) of ESRD where higher in patients who initiated loop diuretics (4.92 (95% CI: 4.34 to 5.59) vs 0.30 (95% CI: 0.28 to 0.33)), but not in those who initiated thiazide diuretics (0.30 (95% CI: 0.20 to 0.46) vs 0.43 (95% CI: 0.40 to 0.46)). However, neither initiation of diuretics or type of diuretic were significantly associated with CKD progression or ESRD after accounting for receipt of other medications and time-dependent confounders using causal inference methods.

Conclusions: The use of thiazide and loop diuretics was not independently associated with an increased risk of CKD progression and/or ESRD in adults with stage 3/4 CKD.
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http://dx.doi.org/10.1136/bmjopen-2021-048755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8808372PMC
January 2022

Deoxycholic Acid and Risks of Cardiovascular Events, ESKD, and Mortality in CKD: The CRIC Study.

Kidney Med 2022 Jan 11;4(1):100387. Epub 2021 Nov 11.

Division of Nephrology and Hypertension, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Rationale & Objective: Elevated levels of deoxycholic acid (DCA) are associated with adverse outcomes and may contribute to vascular calcification in patients with chronic kidney disease (CKD). We tested the hypothesis that elevated levels of DCA were associated with increased risks of cardiovascular disease, CKD progression, and death in patients with CKD.

Study Design: Prospective observational cohort study.

Setting & Participants: We included 3,147 Chronic Renal Insufficiency Cohort study participants who had fasting DCA levels. The average age was 59 ± 11 years, 45.3% were women, 40.6% were African American, and the mean estimated glomerular filtration rate was 42.5 ± 16.0 mL/min/1.73 m.

Predictor: Fasting DCA levels in Chronic Renal Insufficiency Cohort study participants.

Outcomes: Risks of atherosclerotic and heart failure events, end-stage kidney disease (ESKD), and all-cause mortality.

Analytical Approach: We used Tobit regression to identify predictors of DCA levels. We used Cox regression to examine the association between fasting DCA levels and clinical outcomes.

Results: The strongest predictors of elevated DCA levels in adjusted models were increased age and nonuse of statins. The associations between log-transformed DCA levels and clinical outcomes were nonlinear. After adjustment, DCA levels above the median were independently associated with higher risks of ESKD (HR, 2.67; 95% CI, 1.51-4.74) and all-cause mortality (HR, 2.13; 95% CI, 1.25-3.64). DCA levels above the median were not associated with atherosclerotic and heart failure events, and DCA levels below the median were not associated with clinical outcomes.

Limitations: We were unable to measure DCA longitudinally or in urinary or fecal samples, and we were unable to measure other bile acids. We also could not measure many factors that affect DCA levels.

Conclusions: In 3,147 participants with CKD stages 2-4, DCA levels above the median were independently associated with ESKD and all-cause mortality.
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http://dx.doi.org/10.1016/j.xkme.2021.09.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767130PMC
January 2022

Dialysis therapy and mortality in older adults with heart failure and advanced chronic kidney disease: A high-dimensional propensity-matched cohort study.

PLoS One 2022 21;17(1):e0262706. Epub 2022 Jan 21.

Department of Medicine, University of California, San Francisco, CA, United States of America.

Background: Heart failure (HF) and chronic kidney disease (CKD) frequently coexist, and the combination is linked to poor outcomes, but limited data exist to guide optimal management. We evaluated the outcome of dialysis therapy in older patients with HF and advanced CKD.

Methods: We examined adults aged ≥70 years with HF and eGFR ≤20 ml/min/1.73 m2 between 2008-2012 and no prior renal replacement therapy, cancer, cirrhosis or organ transplant. We identified patients who initiated chronic dialysis through 2013 and matched patients who did not initiate dialysis on age, gender, diabetes status, being alive on dialysis initiation date, and a high-dimensional propensity score for starting dialysis. Deaths were identified through 2013. We used Cox regression to evaluate the association of chronic dialysis and all-cause death.

Results: Among 348 adults with HF and advanced CKD who initiated dialysis and 947 matched patients who did not start dialysis, mean age was 80±5 years, 51% were women and 33% were Black. The crude rate of death was high overall but lower in those initiating vs. not initiating chronic dialysis (26.1 vs. 32.1 per 100 person-years, respectively, P = 0.02). In multivariable analysis, dialysis was associated with a 33% (95% Confidence Interval:17-46%) lower adjusted rate of death compared with not initiating dialysis.

Conclusions: Among older adults with HF and advanced CKD, dialysis initiation was associated with lower mortality, but absolute rates of death were very high in both groups. Randomized trials should evaluate net outcomes of dialysis vs. conservative management on length and quality of life in this high-risk population.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0262706PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8782375PMC
February 2022

Angiopoietins as Prognostic Markers for Future Kidney Disease and Heart Failure Events after Acute Kidney Injury.

J Am Soc Nephrol 2022 03 11;33(3):613-627. Epub 2022 Jan 11.

Division of Nephrology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland

Background: The mechanisms underlying long-term sequelae after AKI remain unclear. Vessel instability, an early response to endothelial injury, may reflect a shared mechanism and early trigger for CKD and heart failure.

Methods: To investigate whether plasma angiopoietins, markers of vessel homeostasis, are associated with CKD progression and heart failure admissions after hospitalization in patients with and without AKI, we conducted a prospective cohort study to analyze the balance between angiopoietin-1 (Angpt-1), which maintains vessel stability, and angiopoietin-2 (Angpt-2), which increases vessel destabilization. Three months after discharge, we evaluated the associations between angiopoietins and development of the primary outcomes of CKD progression and heart failure and the secondary outcome of all-cause mortality 3 months after discharge or later.

Results: Median age for the 1503 participants was 65.8 years; 746 (50%) had AKI. Compared with the lowest quartile, the highest quartile of the Angpt-1:Angpt-2 ratio was associated with 72% lower risk of CKD progression (adjusted hazard ratio [aHR], 0.28; 95% confidence interval [CI], 0.15 to 0.51), 94% lower risk of heart failure (aHR, 0.06; 95% CI, 0.02 to 0.15), and 82% lower risk of mortality (aHR, 0.18; 95% CI, 0.09 to 0.35) for those with AKI. Among those without AKI, the highest quartile of Angpt-1:Angpt-2 ratio was associated with 71% lower risk of heart failure (aHR, 0.29; 95% CI, 0.12 to 0.69) and 68% less mortality (aHR, 0.32; 95% CI, 0.15 to 0.68). There were no associations with CKD progression.

Conclusions: A higher Angpt-1:Angpt-2 ratio was strongly associated with less CKD progression, heart failure, and mortality in the setting of AKI.
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http://dx.doi.org/10.1681/ASN.2021060757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8975075PMC
March 2022

Early Pregnancy Blood Pressure Patterns Identify Risk of Hypertensive Disorders of Pregnancy Among Racial and Ethnic Groups.

Hypertension 2022 03 29;79(3):599-613. Epub 2021 Dec 29.

Division of Research, Kaiser Permanente Northern California, Oakland, CA (E.P.G., M.N.N.-H., A.S.G., W.T., S.E.A.).

Background: Hypertensive disorders of pregnancy are a leading cause of severe maternal morbidity and mortality and confer 4-fold higher perinatal mortality in Black women. Early pregnancy blood pressure patterns may differentiate risk of hypertensive disorders of pregnancy.

Methods: This study identified distinct blood pressure trajectories from 0 to 20 weeks' gestation to evaluate subsequent pregnancy-related hypertension in a retrospective cohort of 174 925 women with no prior hypertension or history of preeclampsia, prenatal care entry ≤14 weeks, and a stillborn or live singleton birth delivered at Kaiser Permanente Northern California hospitals in 2009 to 2019. We used electronic health records to obtain clinical outcomes, covariables, and longitudinal outpatient blood pressure measurements ≤20 weeks' gestation (mean 4.1 measurements). Latent class trajectory modeling identified 6 blood pressure groups: ultra-low-declining(referent), low-declining, moderate-fast-decline, low-increasing, moderate-stable, and elevated-stable. Multivariable logistic regression evaluated trajectory group-associations with the odds of preeclampsia/eclampsia and gestational hypertension' and effect modification by race-ethnicity and prepregnancy body size.

Results: Compared with ultra-low-declining, adjusted odds ratios (95% confidence intervals [CIs]) for low-increasing, moderate-stable, and elevated-stable groups were 3.25 (2.7-3.9), 5.3 (4.5-6.3), and 9.2 (7.7-11.1) for preeclampsia/eclampsia' and 6.4 (4.9-8.3), 13.6 (10.5-17.7), and 30.2 (23.2-39.4) for gestational hypertension. Race/ethnicity, and prepregnancy obesity modified the trajectory-group associations with preeclampsia/eclampsia (interaction <0.01), with highest risks for Black, then Hispanic and Asian women for all blood pressure trajectories, and with increasing obesity class.

Conclusions: Early pregnancy blood pressure patterns revealed racial and ethnic differences in associations with preeclampsia/eclampsia risk within equivalent levels and patterns. These blood pressure patterns may improve individual risk stratification permitting targeted surveillance and early mitigation strategies.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.18568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9004135PMC
March 2022

Diagnostic Yield, Outcomes, and Resource Utilization With Different Ambulatory Electrocardiographic Monitoring Strategies.

Am J Cardiol 2022 03 23;166:38-44. Epub 2021 Dec 23.

Division of Research, Kaiser Permanente Northern California, Oakland, California; Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, California; Departments of Epidemiology, Biostatistics and Medicine, University of California, San Francisco, San Francisco, California; Department of Medicine, Stanford University, Stanford, California. Electronic address:

Accurate diagnosis of arrhythmias is improved with longer monitoring duration but can risk delayed diagnosis. We compared diagnostic yield, outcomes, and resource utilization by arrhythmia monitoring strategy in 330 matched adults (mean age 64 years, 40% women, and 30% non-White) without previously documented atrial fibrillation or atrial flutter (AF/AFL) who received ambulatory electrocardiographic monitoring by 14-day Zio XT (patch-based continuous monitor), 24-hour Holter, or 30-day event monitor (external loop recorder) between October 2011 and May 2014. Patients were matched by age, gender, site, likelihood of receiving Zio XT patch, and indication for monitoring, and subsequently followed for monitoring results, management changes, clinical outcomes, and resource utilization. AF/AFL ≥30 seconds was noted in 6% receiving Zio XT versus 0% by Holter (p = 0.04) and 3% by event monitor (p = 0.07). Nonsustained ventricular tachycardia was noted in 24% for Zio XT patch versus 8% (p <0.001) for Holter and 4% (p <0.001) for event monitor. No significant differences between monitoring strategies in outcomes or resource utilization were observed. Prolonged monitoring with 14-day Zio XT patch or 30-day event monitor was superior to 24-hour Holter in detecting new AF/AFL but not different from each other. Documented nonsustained ventricular tachycardia was more frequent with Zio XT than 24-hour Holter and 30-day event monitor without apparent increased risk of adverse outcomes or excess utilization. In conclusion, additional efforts are needed to further personalize electrocardiographic monitoring strategies that optimize clinical management and outcomes.
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http://dx.doi.org/10.1016/j.amjcard.2021.11.027DOI Listing
March 2022

Hyponatremia, Inflammation at Admission, and Mortality in Hospitalized COVID-19 Patients: A Prospective Cohort Study.

Front Med (Lausanne) 2021 2;8:748364. Epub 2021 Dec 2.

Epidemiology Division, Hospital Posadas, Buenos Aires, Argentina.

Systemic inflammation has been associated with severe coronavirus disease 2019 (COVID-19) disease and mortality. Hyponatremia can result from inflammation due to non-osmotic stimuli for vasopressin production. We prospectively studied 799 patients hospitalized with COVID-19 between March 7 and November 7, 2020, at Hospital Posadas in Buenos Aires, Argentina in order to evaluate the association between hyponatremia, inflammation, and its impact on clinical outcomes. Admission biochemistries, high-sensitivity C-reactive protein (hsCRP), ferritin, patient demographics, and outcome data were recorded. Outcomes (within 30 days after symptoms) evaluated included ICU admission, mechanical ventilation, dialysis-requiring acute kidney injury (AKI), and in-hospital mortality. Length of hospital stay (in days) were evaluated using comprehensive data from the EHR. Hyponatremia (median Na = 133 mmol/L) was present on admission in 366 (45.8%). Hyponatremic patients had higher hsCRP (median 10.3 [IR 4.8-18.4] mg/dl vs. 6.6 [IR 1.6-14.0] mg/dl, < 0.01) and ferritin levels (median 649 [IQR 492-1,168] ng/dl vs. 393 [IQR 156-1,440] ng/dl, = 0.02) than normonatremic patients. Hyponatremia was associated with higher odds of an abnormal hsCRP (unadjusted OR 5.03, 95%CI: 2.52-10.03), and remained significant after adjustment for potential confounders (adjusted OR 4.70 [95%CI: 2.33-9.49], < 0.01). Hyponatremic patients had increased mortality on unadjusted (HR 3.05, 95%CI: 2.14-4.34) and adjusted (HR 2.76, 95%CI:1.88-4.06) in Cox proportional hazard models. Crude 30-day survival was lower for patients with hyponatremia at admission (mean [SD] survival 22.1 [0.70] days) compared with patients who were normonatremic (mean [SD] survival 27.2 [0.40] days, < 0.01). Mild hyponatremia on admission is common, is associated with systemic inflammation and is an independent risk factor for hospital mortality. www.ClinicalTrials.gov, identifier NCT04493268.
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http://dx.doi.org/10.3389/fmed.2021.748364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8674434PMC
December 2021

Management of Adults with Newly Diagnosed Atrial Fibrillation with and without CKD.

J Am Soc Nephrol 2022 02 17;33(2):442-453. Epub 2021 Dec 17.

Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, California.

Background: Atrial fibrillation (AF) is highly prevalent in CKD and is associated with worse cardiovascular and kidney outcomes. Limited data exist on use of AF pharmacotherapies and AF-related procedures by CKD status. We examined a large "real-world" contemporary population with incident AF to study the association of CKD with management of AF.

Methods: We identified patients with newly diagnosed AF between 2010 and 2017 from two large, integrated health care delivery systems. eGFR (≥60, 45-59, 30-44, 15-29, <15 ml/min per 1.73 m) was calculated from a minimum of two ambulatory serum creatinine measures separated by ≥90 days. AF medications and procedures were identified from electronic health records. We performed multivariable Fine-Gray subdistribution hazards regression to test the association of CKD severity with receipt of targeted AF therapies.

Results: Among 115,564 patients with incident AF, 34% had baseline CKD. In multivariable models, compared with those with eGFR >60 ml/min per 1.73 m, patients with eGFR 30-44 (adjusted hazard ratio [aHR] 0.91; 95% CI, 0.99 to 0.93), 15-29 (aHR, 0.78; 95% CI, 0.75 to 0.82), and <15 ml/min per 1.73 m (aHR, 0.64; 95% CI, 0.58-0.70) had lower use of any AF therapy. Patients with eGFR 15-29 ml/min per 1.73 m had lower adjusted use of rate control agents (aHR, 0.61; 95% CI, 0.56 to 0.67), warfarin (aHR, 0.89; 95% CI, 0.84 to 0.94), and DOACs (aHR, 0.23; 95% CI, 0.19 to 0.27) compared with patients with eGFR >60 ml/min per 1.73 m. These associations were even stronger for eGFR <15 ml/min per 1.73 m. There was also a graded association between CKD severity and receipt of AF-related procedures (vs eGFR >60 ml/min per 1.73 m): eGFR 30-44 ml/min per 1.73 (aHR, 0.78; 95% CI, 0.70 to 0.87), eGFR 15-29 ml/min per 1.73 m (aHR, 0.73; 95% CI, 0.61 to 0.88), and eGFR <15 ml/min per 1.73 m (aHR, 0.48; 95% CI, 0.31 to 0.74).

Conclusions: In adults with newly diagnosed AF, CKD severity was associated with lower receipt of rate control agents, anticoagulation, and AF procedures. Additional data on efficacy and safety of AF therapies in CKD populations are needed to inform management strategies.
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http://dx.doi.org/10.1681/ASN.2021060744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8819992PMC
February 2022

Human Immunodeficiency Virus Infection and Variation in Heart Failure Risk by Age, Sex, and Ethnicity: The HIV HEART Study.

Mayo Clin Proc 2022 03 13;97(3):465-479. Epub 2021 Dec 13.

Division of Research, Kaiser Permanente Northern California, Oakland.

Objectives: To evaluate the risk of heart failure (HF) linked to human immunodeficiency virus (HIV) infection, how risk varies by demographic characteristics, and whether it is explained by atherosclerotic disease or risk factor treatment.

Patients And Methods: We performed a retrospective cohort study of persons with HIV (PWHs) from January 1, 2000, through December 31, 2016, frequency-matched 1:10 to persons without HIV on year of entry, age, sex, race/ethnicity, and treating facility. We evaluated the risk of incident HF associated with HIV infection, overall and by left ventricular systolic function, and whether HF risk varied by demographic characteristics.

Results: Among 38,868 PWHs and 386,586 matched persons without HIV, mean ± SD age was 41.4±10.8 years, with 12.3% female, 21.1% Black, 20.5% Hispanic, and 3.9% Asian/Pacific Islander. During median follow-up of 3.8 years (interquartile range, 1.4-9.0 years), the rate (per 100 person-years) of incident HF was 0.23 in PWHs vs 0.15 in those without HIV (P<.001). The PWHs had a higher adjusted HF rate (adjusted hazard ratio [aHR], 1.73; 95% confidence interval [CI], 1.57 to 1.91), which was only modestly attenuated after accounting for interim acute coronary syndrome events. Results were similar by systolic function category. The adjusted risk of HF in PWHs was more prominent for those 40 years and younger (aHR, 2.45; 95% CI, 1.92 to 3.03), women (aHR, 2.48; 95% CI, 1.90 to 3.26), and Asian/Pacific Islanders (aHR, 2.46; 95% CI, 1.27 to 4.74).

Conclusion: HIV infection increases the risk of HF, which varied by demographic characteristics and was not primarily mediated through atherosclerotic disease pathways or differential use of cardiopreventive medications.
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http://dx.doi.org/10.1016/j.mayocp.2021.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9074114PMC
March 2022

A Natural Language Processing-Based Approach for Identifying Hospitalizations for Worsening Heart Failure Within an Integrated Health Care Delivery System.

JAMA Netw Open 2021 11 1;4(11):e2135152. Epub 2021 Nov 1.

Division of Research, Kaiser Permanente Northern California, Oakland.

Importance: The current understanding of epidemiological mechanisms and temporal trends in hospitalizations for worsening heart failure (WHF) is based on claims and national reporting databases. However, these data sources are inherently limited by the accuracy and completeness of diagnostic coding and/or voluntary reporting.

Objective: To assess the overall burden of and temporal trends in the rate of hospitalizations for WHF.

Design, Setting, And Participants: This cohort study, performed from January 1, 2010, to December 31, 2019, used electronic health record (EHR) data from a large integrated health care delivery system.

Exposures: Calendar year trends.

Main Outcomes And Measures: Hospitalizations for WHF (ie, excluding observation stays) were defined as 1 symptom or more, 2 objective findings or more including 1 sign or more, and 2 doses or more of intravenous loop diuretics and/or new hemodialysis or continuous kidney replacement therapy. Symptoms and signs were identified using natural language processing (NLP) algorithms applied to EHR data.

Results: The study population was composed of 118 002 eligible patients experiencing 287 992 unique hospitalizations (mean [SD] age, 75.6 [13.1] years; 147 203 [51.1%] male; 1655 [0.6%] American Indian or Alaska Native, 28 451 [9.9%] Asian or Pacific Islander, 34 903 [12.1%] Black, 23 452 [8.1%] multiracial, 175 840 [61.1%] White, and 23 691 [8.2%] unknown), including 65 357 with a principal discharge diagnosis and 222 635 with a secondary discharge diagnosis of HF. The study population included 59 868 patients (20.8%) with HF with a reduced ejection fraction (HFrEF) (<40%), 33 361 (11.6%) with HF with a midrange EF (HFmrEF) (40%-49%), 142 347 (49.4%) with HF with a preserved EF (HFpEF) (≥50%), and 52 416 (18.2%) with unknown EF. A total of 58 042 admissions (88.8%) with a primary discharge diagnosis of HF and 62 764 admissions (28.2%) with a secondary discharge diagnosis of HF met the prespecified diagnostic criteria for WHF. Overall, hospitalizations for WHF identified on NLP-based algorithms increased from 5.2 to 7.6 per 100 hospitalizations per year during the study period. Subgroup analyses found an increase in hospitalizations for WHF based on NLP from 1.5 to 1.9 per 100 hospitalizations for HFrEF, from 0.6 to 1.0 per 100 hospitalizations for HFmrEF, and from 2.6 to 3.9 per 100 hospitalizations for HFpEF.

Conclusions And Relevance: The findings of this cohort study suggest that the burden of hospitalizations for WHF may be more than double that previously estimated using only principal discharge diagnosis. There has been a gradual increase in the rate of hospitalizations for WHF with a more noticeable increase observed for HFpEF.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.35152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8609413PMC
November 2021

Change in ankle-brachial index and mortality among individuals with chronic kidney disease: findings from the Chronic Renal Insufficiency Cohort Study.

Nephrol Dial Transplant 2021 12;36(12):2224-2231

Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.

Background: Patients with chronic kidney disease (CKD) have an increased risk of peripheral arterial disease (PAD). The ankle-brachial index (ABI), a noninvasive measure of PAD, is a predictor of adverse events among individuals with CKD. In general populations, changes in ABI have been associated with mortality, but this association is not well understood among patients with CKD.

Methods: We conducted a prospective study of 2920 participants in the Chronic Renal Insufficiency Cohort Study without lower extremity revascularization or amputation at baseline and with at least one follow-up ABI measurement (taken at annual visits) during the first 4 years of follow-up. The ABI was obtained by the standard protocol.

Results: In Cox proportional hazard regression analyses, we found a U-shaped association of average annual change in ABI with all-cause mortality. After adjusting for baseline ABI and other covariates, compared with participants with an average annual change in ABI of 0-<0.02, individuals with an average annual change in ABI <-0.04 or ≥0.04 had multivariable-adjusted hazard ratios (HRs) of 1.81 [95% confidence interval (CI) 1.34-2.44) and 1.42 (95% CI 1.12-1.82) for all-cause mortality, respectively. Compared with the cumulative average ABI of 1.0-<1.4, multivariable-adjusted HRs for those with a cumulative average ABI of <0.9, 0.9-<1.0 and ≥1.4 were 1.93 (95% CI 1.42-2.61), 1.20 (0.90-1.62) and 1.31 (0.94-1.82), respectively.

Conclusions: This study indicates both larger decreases and increases in average annual changes in ABI (>0.04/year) were associated with higher mortality risk. Monitoring changes in ABI over time may facilitate risk stratification for mortality among individuals with CKD.
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http://dx.doi.org/10.1093/ndt/gfaa246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8643604PMC
December 2021

Population-based identification and temporal trend of children with primary nephrotic syndrome: The Kaiser Permanente nephrotic syndrome study.

PLoS One 2021 14;16(10):e0257674. Epub 2021 Oct 14.

Division of Research, Kaiser Permanente Northern California, Oakland, CA, United States of America.

Introduction: Limited population-based data exist about children with primary nephrotic syndrome (NS).

Methods: We identified a cohort of children with primary NS receiving care in Kaiser Permanente Northern California, an integrated healthcare delivery system caring for >750,000 children. We identified all children <18 years between 1996 and 2012 who had nephrotic range proteinuria (urine ACR>3500 mg/g, urine PCR>3.5 mg/mg, 24-hour urine protein>3500 mg or urine dipstick>300 mg/dL) in laboratory databases or a diagnosis of NS in electronic health records. Nephrologists reviewed health records for clinical presentation and laboratory and biopsy results to confirm primary NS.

Results: Among 365 cases of confirmed NS, 179 had confirmed primary NS attributed to presumed minimal change disease (MCD) (72%), focal segmental glomerulosclerosis (FSGS) (23%) or membranous nephropathy (MN) (5%). The overall incidence of primary NS was 1.47 (95% Confidence Interval:1.27-1.70) per 100,000 person-years. Biopsy data were available in 40% of cases. Median age for patients with primary NS was 6.9 (interquartile range:3.7 to 12.9) years, 43% were female and 26% were white, 13% black, 17% Asian/Pacific Islander, and 32% Hispanic.

Conclusion: This population-based identification of children with primary NS leveraging electronic health records can provide a unique approach and platform for describing the natural history of NS and identifying determinants of outcomes in children with primary NS.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0257674PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516311PMC
November 2021

Triglyceride Levels and Residual Risk of Atherosclerotic Cardiovascular Disease Events and Death in Adults Receiving Statin Therapy for Primary or Secondary Prevention: Insights From the KP REACH Study.

J Am Heart Assoc 2021 10 8;10(20):e020377. Epub 2021 Oct 8.

Division of Research Kaiser Permanente Northern California Oakland CA.

Background Patients with risk factors or established atherosclerotic cardiovascular disease remain at high-risk for ischemic events. Triglyceride levels may play a causal role. Methods and Results We performed a retrospective study of adults aged ≥45 years receiving statin therapy, with a low-density lipoprotein cholesterol of 41 to 100 mg/dL, and ≥1 risk factor or established atherosclerotic cardiovascular disease between 2010 and 2017. Outcomes included death, all-cause hospitalization, and major adverse cardiovascular events (myocardial infarction, stroke, or peripheral artery disease). The study sample included 373 389 primary prevention patients and 97 832 secondary prevention patients. The primary prevention cohort had a mean age of 65±10 years, with 51% women and 44% people of color, whereas the secondary prevention cohort had a mean age of 71±11 years, with 37% women and 32% people of color. Median triglyceride levels for the primary and secondary prevention cohorts were 122 mg/dL (interquartile range, 88-172 mg/dL) and 116 mg/dL (interquartile range, 84-164 mg/dL), respectively. In multivariable analyses, primary prevention patients with triglyceride levels ≥150 mg/dL were at lower adjusted risk of death (hazard ratio [HR], 0.91; 95% CI, 0.89-0.94) and higher risk of major adverse cardiovascular events (HR, 1.14; 95% CI, 1.05-1.24). In the secondary prevention cohort, patients with triglyceride levels ≥150 mg/dL were at lower adjusted risk of death (HR, 0.95; 95% CI, 0.92-0.97) and higher risk of all-cause hospitalization (HR, 1.03; 95% CI, 1.01-1.05) and major adverse cardiovascular events (HR, 1.04; 95% CI, 1.05-1.24). Conclusions In a contemporary cohort receiving statin therapy, elevated triglyceride levels were associated with a greater risk of atherosclerotic cardiovascular disease events and lower risk of death.
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http://dx.doi.org/10.1161/JAHA.120.020377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8751901PMC
October 2021

Physician adjudication of angioedema diagnosis codes in a population of patients with heart failure prescribed angiotensin-converting enzyme inhibitor therapy.

Pharmacoepidemiol Drug Saf 2021 12 1;30(12):1630-1634. Epub 2021 Oct 1.

Center for Health Research, Kaiser Permanente Northwest, Portland, Oregon, USA.

Purpose: Our objective was to calculate the positive predictive value (PPV) of the ICD-9 diagnosis code for angioedema when physicians adjudicate the events by electronic health record review. Our secondary objective was to evaluate the inter-rater reliability of physician adjudication.

Methods: Patients from the Cardiovascular Research Network previously diagnosed with heart failure who were started on angiotensin-converting enzyme inhibitors (ACEI) during the study period (July 1, 2006 through September 30, 2015) were included. A team of two physicians per participating site adjudicated possible events using electronic health records for all patients coded for angioedema for a total of five sites. The PPV was calculated as the number of physician-adjudicated cases divided by all cases with the diagnosis code of angioedema (ICD-9-CM code 995.1) meeting the inclusion criteria. The inter-rater reliability of physician teams, or kappa statistic, was also calculated.

Results: There were 38 061 adults with heart failure initiating ACEI in the study (21 489 patient-years). Of 114 coded events that were adjudicated by physicians, 98 angioedema events were confirmed for a PPV of 86% (95% CI: 80%, 92%). The kappa statistic based on physician inter-rater reliability was 0.65 (95% CI: 0.47, 0.82).

Conclusions: ICD-9 diagnosis code of 995.1 (angioneurotic edema, not elsewhere classified) is highly predictive of angioedema in adults with heart failure exposed to ACEI.
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http://dx.doi.org/10.1002/pds.5361DOI Listing
December 2021

Race, Genetic Ancestry, and Estimating Kidney Function in CKD.

N Engl J Med 2021 11 23;385(19):1750-1760. Epub 2021 Sep 23.

From the Division of Nephrology, Department of Medicine (C.H., A.N.M., A.S.G.), and the Departments of Epidemiology and Biostatistics (A.S.G.), University of California, San Francisco, San Francisco, the Division of Research, Kaiser Permanente Northern California, Oakland (C.H., R.V.P., T.C.T., A.S.G.), the Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena (A.S.G.), and the Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Palo Alto (A.S.G.) - all in California; the Department of Biostatistics, Epidemiology, and Informatics and the Center for Clinical Epidemiology and Biostatistics (W.Y., J.W., H.I.F.), the Division of Division of Renal-Electrolyte and Hypertension (D.L.C.), and the Department of Medicine (R.R.T.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; the Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine (A.H.A., J.H., K.T.M.) and the Tulane University Translational Science Institute (A.H.A., J.H., K.T.M.), New Orleans; the Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, and the Welch Center for Prevention, Epidemiology, and Clinical Research, Baltimore (T.K.C.), and the Division of Kidney, Urologic, and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda (A.P.) - all in Maryland; the Division of Nephrology, Department of Internal Medicine, Wayne State University, Detroit (M.J.M.); the Division of Nephrology, Department of Medicine, University of Illinois at Chicago (J.P.L.), and the Section of General Internal Medicine, Department of Medicine, University of Chicago (M.R.S.) - both in Chicago; the Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson (T.S.); the Section of Nephrology, Boston University School of Medicine and Boston Medical Center, Boston (S.S.W.); and the Division of Nephrology, Department of Medicine, and Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (M.W.).

Background: The inclusion of race in equations to estimate the glomerular filtration rate (GFR) has become controversial. Alternative equations that can be used to achieve similar accuracy without the use of race are needed.

Methods: In a large national study involving adults with chronic kidney disease, we conducted cross-sectional analyses of baseline data from 1248 participants for whom data, including the following, had been collected: race as reported by the participant, genetic ancestry markers, and the serum creatinine, serum cystatin C, and 24-hour urinary creatinine levels.

Results: Using current formulations of GFR estimating equations, we found that in participants who identified as Black, a model that omitted race resulted in more underestimation of the GFR (median difference between measured and estimated GFR, 3.99 ml per minute per 1.73 m of body-surface area; 95% confidence interval [CI], 2.17 to 5.62) and lower accuracy (percent of estimated GFR within 10% of measured GFR [P], 31%; 95% CI, 24 to 39) than models that included race (median difference, 1.11 ml per minute per 1.73 m; 95% CI, -0.29 to 2.54; P, 42%; 95% CI, 34 to 50). The incorporation of genetic ancestry data instead of race resulted in similar estimates of the GFR (median difference, 1.33 ml per minute per 1.73 m; 95% CI, -0.12 to 2.33; P, 42%; 95% CI, 34 to 50). The inclusion of non-GFR determinants of the serum creatinine level (e.g., body-composition metrics and urinary excretion of creatinine) that differed according to race reported by the participants and genetic ancestry did not eliminate the misclassification introduced by removing race (or ancestry) from serum creatinine-based GFR estimating equations. In contrast, the incorporation of race or ancestry was not necessary to achieve similarly statistically unbiased (median difference, 0.33 ml per minute per 1.73 m; 95% CI, -1.43 to 1.92) and accurate (P, 41%; 95% CI, 34 to 49) estimates in Black participants when GFR was estimated with the use of cystatin C.

Conclusions: The use of the serum creatinine level to estimate the GFR without race (or genetic ancestry) introduced systematic misclassification that could not be eliminated even when numerous non-GFR determinants of the serum creatinine level were accounted for. The estimation of GFR with the use of cystatin C generated similar results while eliminating the negative consequences of the current race-based approaches. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.).
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http://dx.doi.org/10.1056/NEJMoa2103753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8994696PMC
November 2021
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