Publications by authors named "Edward D Siew"

Key Points: AKI is common among hospitalized patients. However, the contribution of neighborhood social determinants of health to AKI risk is not known. We found that among 26,769 hospitalized patients, 26% developed AKI.

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Pulmonary hypertension (PH) is common in patients with chronic kidney disease (CKD) or kidney failure, with an estimated prevalence of up to 78% in those referred for right-heart catheterization. PH is independently associated with adverse outcomes in CKD, raising the possibility that early detection and appropriate management of PH might improve outcomes in at-risk patients. Among patients with PH, the prevalence of CKD stages 3 and 4 is estimated to be as high as 36%, and CKD is also independently associated with adverse outcomes.

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Article Synopsis
  • Acute kidney injury (AKI) is a serious issue in hospitalized patients, prompting a study that analyzed genetic factors in a large cohort from the Million Veteran Program and Vanderbilt University Medical Center.
  • The study included 54,488 patients with AKI and 138,051 without, identifying two significant genetic loci associated with AKI: one near the FTO gene related to obesity and another near SHROOM3 linked to kidney function.
  • The research suggests that genetics may play a role in the risk of developing AKI, with factors like body mass index and diabetes potentially influencing the association with the FTO locus.
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Introduction: Acute kidney injury (AKI) is associated with increased risk of heart failure (HF). Determining the type of HF experienced by AKI survivors (heart failure with preserved or reduced ejection fraction, HFpEF or HFrEF) could suggest potential mechanisms underlying the association and opportunities for improving post-AKI care.

Methods: In this retrospective study of adults within the Vanderbilt University health system with a diagnosis of HF, we tested whether AKI events in the two years preceding incident HF associated more with HFpEF or HFrEF while controlling for known predictors.

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Key Points: This study highlights that AKI is associated with long-term cognitive decline. Soluble TNF receptor 1 concentrations seem to mediate a significant proportion of the risk of long-term cognitive impairment after AKI.

Background: Cognitive dysfunction is a well-known complication of CKD, but it is less known whether cognitive decline occurs in survivors after AKI.

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Article Synopsis
  • The study aimed to investigate how pharmacists contribute to the postdischarge care of patients suffering from kidney disease.
  • It analyzed various interventions from 10 studies, focusing on areas like medication management and patient education, with some showing positive outcomes related to patient care metrics.
  • Ultimately, the findings highlight the pharmacist's potential role in multidisciplinary teams but indicate variability in their effectiveness and lack of standardized practices.
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Importance: Cefepime and piperacillin-tazobactam are commonly administered to hospitalized adults for empirical treatment of infection. Although piperacillin-tazobactam has been hypothesized to cause acute kidney injury and cefepime has been hypothesized to cause neurological dysfunction, their comparative safety has not been evaluated in a randomized clinical trial.

Objective: To determine whether the choice between cefepime and piperacillin-tazobactam affects the risks of acute kidney injury or neurological dysfunction.

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  • African Americans are more susceptible to chronic kidney disease (CKD) partly due to high-risk variants in the APOL1 gene, specifically G1/G2 variants, but a different variant, p.N264K, appears to lower this risk significantly.
  • A study of over 121,000 participants showed that those with the p.N264K variant had CKD and end-stage kidney disease (ESKD) risks comparable to individuals with low-risk APOL1 variants.
  • Research indicates that p.N264K blocks harmful pore-forming functions of APOL1 high-risk variants, suggesting that drugs mimicking this protective mutation could potentially prevent or treat kidney disease related to APOL1.
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Biomarkers of tubular function such as epidermal growth factor (EGF) may improve prognostication of participants at highest risk for chronic kidney disease (CKD) after hospitalization. To examine this, we measured urinary EGF (uEGF) from samples collected in the Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) Study, a multi-center, prospective, observational cohort of hospitalized participants with and without AKI. Cox proportional hazards regression was used to investigate the association of uEGF/Cr at hospitalization, three months post-discharge, and the change between these time points with major adverse kidney events (MAKE): CKD incidence, progression, or development of kidney failure.

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Diuresis to achieve decongestion is a central aim of therapy in patients hospitalized for acute decompensated heart failure (ADHF). While multiple clinical trials have investigated initial diuretic strategies for a designated period of time, there is a paucity of evidence to guide diuretic titration strategies continued until decongestion is achieved. The use of urine chemistries (urine sodium and creatinine) in a natriuretic response prediction equation accurately estimates natriuresis in response to diuretic dosing, but a randomized clinical trial is needed to compare a urine chemistry-guided diuresis strategy with a strategy of usual care.

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Key Points: Two genetic variants in the DISP1-TLR5 gene locus were associated with risk of AKI. DISP1 and TLR5 were differentially regulated in kidney biopsy tissue from patients with AKI compared with no AKI.

Background: Although common genetic risks for CKD are well established, genetic factors influencing risk for AKI in hospitalized patients are poorly understood.

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Significance Statement: Rapid progression of CKD is associated with poor clinical outcomes. Most previous studies looking for genetic factors associated with low eGFR have used cross-sectional data. The authors conducted a meta-analysis of genome-wide association studies of eGFR decline among 116,870 participants with CKD, focusing on longitudinal data.

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Introduction: Nephrotoxin exposure is significantly associated with acute kidney injury (AKI) development. A standardized list of nephrotoxic medications to surveil and their perceived nephrotoxic potential (NxP) does not exist for non-critically ill patients.

Objective: This study generated consensus on the nephrotoxic effect of 195 medications used in the non-intensive care setting.

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Rationale & Objective: Acute kidney injury (AKI) is a heterogeneous clinical syndrome with varying causes, pathophysiology, and outcomes. We incorporated plasma and urine biomarker measurements to identify AKI subgroups (subphenotypes) more tightly linked to underlying pathophysiology and long-term clinical outcomes.

Study Design: Multicenter cohort study.

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Article Synopsis
  • Researchers identified four distinct subphenotypes of Acute Kidney Injury (AKI) using a comprehensive approach that included various biomarkers and clinical evaluations.
  • Each subphenotype exhibited unique characteristics: Subphenotype 1 showed high kidney injury and cardiac biomarkers, Subphenotype 2 had elevated uromodulin levels, Subphenotype 3 was linked to severe heart-related markers, and Subphenotype 4 was mainly associated with sepsis and significant inflammation.
  • Findings indicated that Subphenotypes 3 and 4 had a notably higher risk of death compared to Subphenotype 2, suggesting that a more nuanced understanding of AKI could improve patient outcomes.
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BACKGROUNDLongitudinal investigations of murine acute kidney injury (AKI) suggest that injury and inflammation may persist long after the initial insult. However, the evolution of these processes and their prognostic values are unknown in patients with AKI.METHODSIn a prospective cohort of 656 participants hospitalized with AKI, we measured 7 urine and 2 plasma biomarkers of kidney injury, inflammation, and tubular health at multiple time points from the diagnosis to 12 months after AKI.

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Introduction: Antibiotics are time-critical in the management of sepsis. When infectious organisms are unknown, patients are treated with empiric antibiotics to include coverage for gram-negative organisms, such as antipseudomonal cephalosporins and penicillins. However, in observational studies, some antipseudomonal cephalosporins (eg, cefepime) are associated with neurologic dysfunction while the most common antipseudomonal penicillin (piperacillin-tazobactam) is associated with acute kidney injury (AKI).

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Cannabis consumption for recreational and medical use is increasing worldwide. However, the long-term effects on kidney health and disease are largely unknown. analysis of cannabis use as a risk factor for kidney disease was performed using data from the Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) study that enrolled hospitalized adults with and without acute kidney injury from four U.

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Background: Prior studies support a genetic basis for postoperative acute kidney injury (AKI). We conducted a genome-wide association study (GWAS), assessed the clinical utility of a polygenic risk score (PRS), and estimated the heritable component of AKI in patients who underwent noncardiac surgery.

Methods: We performed a retrospective large-scale genome-wide association study followed by a meta-analysis of patients who underwent noncardiac surgery at the Vanderbilt University Medical Center ("Vanderbilt" cohort) or Michigan Medicine, the academic medical center of the University of Michigan ("Michigan" cohort).

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Article Synopsis
  • Developed machine learning models were used to improve mortality predictions for patients with acute kidney injury (AKI) who require renal replacement therapy (RRT), as existing scoring systems were found to be poorly calibrated.
  • The models were trained on data from MIMIC and eICU databases, with comparisons made to traditional scoring systems like SOFA and HELENICC based on various performance metrics.
  • The XGBoost model outperformed all other methods, achieving the highest accuracy and calibration in predicting mortality among these patients.
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Introduction: Common variants in the gene are considered an evolutionary adaptation against urinary tract infections (UTIs) and have been implicated in kidney stone formation, chronic kidney disease (CKD), and hypertension. However, differences in variant-phenotype associations across population groups are unclear.

Methods: We tested associations between variants and up to 1528 clinical diagnosis codes mapped to phenotype groups in the Million Veteran Program (MVP), using published phenome-wide association study (PheWAS) methodology.

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Since the description by William Heberden (1), AKI has remained a prominent complication of critical illness. Beyond KRT, treatment has been limited by the capacity to phenotype this condition. Here, we chronicle the evolution of attempts to classify AKI, including the adoption of consensus definitions, the expansion of diagnosis and prognosis with novel biomarkers, and emerging tools such as artificial intelligence (AI).

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Importance: Coronavirus disease 2019 (COVID-19) confers significant risk of acute kidney injury (AKI). Patients with COVID-19 with AKI have high mortality rates.

Objective: Individuals with African ancestry with 2 copies of apolipoprotein L1 (APOL1) variants G1 or G2 (high-risk group) have significantly increased rates of kidney disease.

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