Risk Prediction for Acute Kidney Injury in Patients Hospitalized With COVID-19

McAdams, Meredith; Xu, Pin; Saleh, Sameh N; Ostrosky-Frid, Mauricio; Gregg, L. Parker; Willett, Duwayne L; Velasco, Ferdinand; Lehmann, Christoph U.; Hedayati, S. Susan

doi:10.1016/j.xkme.2022.100463

Cited by 6 publications

(10 citation statements)

References 43 publications

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“…Furthermore, we observed increased expression levels of TLRs, cytokines, and chemokines in the kidney, especially in Delta-infected mice, which may lead to acute kidney injury (AKI) as a complication of long-term COVID-19 infections. Our results are consistent with several studies reporting that patients with COVID-19 infected with the Delta variant experienced lingering AKI [49,50].…”

Section: Discussionsupporting

confidence: 93%

Comparison of the Pathogenicity of SARS-CoV-2 Delta and Omicron Variants by Analyzing the Expression Patterns of Immune Response Genes in K18-hACE2 Transgenic Mice

Kuruppuarachchi¹,

Jang²,

Seo³

2022

Front. Biosci. (Landmark Ed)

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Background:The recently emerged variants of the severe acute respiratory coronavirus 2 (SARS-CoV-2) pose a threat to public health. Understanding the pathogenicity of these variants is a salient factor in the development of effective SARS-CoV-2 therapeutics. This study aimed to compare the expression patterns of genes involved in immune responses in K18-hACE2 mice infected with the wild-type, Delta, and Omicron SARS-CoV-2 variants. Methods: K18-hACE2 mice were intranasally infected with either wild-type (B.1), Delta (B.1.617.2), or Omicron (B.1.1.529) variants. On day 6 post-infection, lung, brain, and kidney tissues were collected from each variantinfected group. The mRNA expression levels of 39 immune response genes in all three groups were compared by RT-qPCR. Viral titers were measured using the median tissue culture infectious dose (TCID50) assay and expressed as Log10 TCID50/0.1 g. The statistical significance of the differences in gene expression was determined by one-way analysis of variance (ANOVA) (alpha = 0.05). Results: The expression of toll-like receptors (TLRs) was upregulated in the lung and brain tissues of the wild-type-and Delta-infected groups but not in those of the Omicron-infected group. The highest expression of cytokines, including interleukin (IL)-1α, IL-1β, IL-17α, interferon, and tumor necrosis factors, was observed in the lungs of mice infected with the wild-type variant. Additionally, CCL4, CCL11, CXCL9, and CXCL10 were upregulated (>3-fold) in wild-type-infected mice, with markedly higher expressions in the brain than in the lungs. Most of the apoptotic factors were mainly expressed in the brain tissues of Omicron-infected mice (caspase 8, caspase 9, p53, Bax, Bak, BCL-2, and Bcl-XL), whereas neither the lung nor kidney showed more than 3-fold upregulation of these apoptotic factors. Conclusions: Collectively, our findings revealed that the wild-type SARS-CoV-2 variant exhibited the highest pathogenicity, followed by the Delta variant, then the Omicron variant.

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Section: Discussionsupporting

confidence: 93%

Comparison of the Pathogenicity of SARS-CoV-2 Delta and Omicron Variants by Analyzing the Expression Patterns of Immune Response Genes in K18-hACE2 Transgenic Mice

Kuruppuarachchi¹,

Jang²,

Seo³

2022

Front. Biosci. (Landmark Ed)

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“…Nested models for AKI were built using pre-specified covariates based on clinical plausibility that included demographics, medical comorbidities, and baseline laboratory values associated with COVID-19 disease severity, as previously described. 8 Models were created in an Inception Cohort , which contained hospitalizations between March 1, 2020 and March 1, 2021, when almost all COVID-19 cases were caused by the wild-type variant. The final model included age, sex, race, ethnicity, smoking, comorbidities (hypertension, diabetes mellitus, CKD, coronary artery disease (CAD), chronic heart failure (CHF)), angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use, and initial laboratory values and inflammatory biomarkers (white blood cell count, hemoglobin, ferritin, hsCRP, D-dimer).…”

Section: Methodsmentioning

confidence: 99%

“…The variables with the highest importance in the final model were a history of chronic kidney disease (CKD), high-sensitivity C-reactive protein (hsCRP), ferritin, and D-dimer levels. 8 However, this model was developed and validated prior to the Omicron surge. Given the differences between variants, characteristics of affected patients, and changes in practice patterns throughout the pandemic, we aimed to extend our findings by validating and assessing the performance of our predictive AKI model in hospitalized COVID-19 patients during periods when COVID-19 cases were almost exclusively caused by the Delta and Omicron variants.…”

Section: Introductionmentioning

confidence: 99%

Validation of a predictive model for hospital-acquired acute kidney injury with emergence of SARS-CoV-2 variants

McAdams

Gregg

et al. 2023

Journal of Investigative Medicine

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We previously developed and validated a model to predict acute kidney injury (AKI) in hospitalized coronavirus disease 2019 (COVID-19) patients and found that the variables with the highest importance included a history of chronic kidney disease and markers of inflammation. Here, we assessed model performance during periods when COVID-19 cases were attributable almost exclusively to individual variants. Electronic Health Record data were obtained from patients admitted to 19 hospitals. The outcome was hospital-acquired AKI. The model, previously built in an Inception Cohort, was evaluated in Delta and Omicron cohorts using model discrimination and calibration methods. A total of 9104 patients were included, with 5676 in the Inception Cohort, 2461 in the Delta cohort, and 967 in the Omicron cohort. The Delta Cohort was younger with fewer comorbidities, while Omicron patients had lower rates of intensive care compared with the other cohorts. AKI occurred in 13.7% of the Inception Cohort, compared with 13.8% of Delta and 14.4% of Omicron (Omnibus p = 0.84). Compared with the Inception Cohort (area under the curve (AUC): 0.78, 95% confidence interval (CI): 0.76–0.80), the model showed stable discrimination in the Delta (AUC: 0.78, 95% CI: 0.75–0.80, p = 0.89) and Omicron (AUC: 0.74, 95% CI: 0.70–0.79, p = 0.37) cohorts. Estimated calibration index values were 0.02 (95% CI: 0.01–0.07) for Inception, 0.08 (95% CI: 0.05–0.17) for Delta, and 0.12 (95% CI: 0.04–0.47) for Omicron cohorts, p = 0.10 for both Delta and Omicron vs Inception. Our model for predicting hospital-acquired AKI remained accurate in different COVID-19 variants, suggesting that risk factors for AKI have not substantially evolved across variants.

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“…Requests involving data from both partners undergo an expedited review, approval, and procurement steps (facilitated by the master DUA) at each institution. The DUA architecture has also allowed construction of common THR‐UTSW data repositories, one of which was used recently to develop a prediction model for acute kidney injury in patients hospitalized with COVID‐19 11 . Work is underway to expand the content and granularity of these common data repositories, particularly in terms of bringing in historically unstructured EHR data elements into more easily extracted and usable formats.…”

Section: Methods: Program Design and Operational Componentsmentioning

confidence: 99%

“…The DUA architecture has also allowed construction of common THR-UTSW data repositories, one of which was used recently to develop a prediction model for acute kidney injury in patients hospitalized with COVID-19. 11 Work is underway to expand the content and granularity of these common data repositories, particularly in terms of bringing in historically unstructured EHR data elements into more easily extracted and usable formats. The THR Clinical Scholars Program emphasizes projects with a more proximal care delivery application, whereas proposals earlier in the translational pathway are likely to be directed to the CTSA.…”

Section: Data Use and Sharingmentioning

confidence: 99%

The Texas Health Resources Clinical Scholars Program: Learning healthcare system workforce development through embedded translational research

Masica

Velasco

Nelson

et al. 2022

Learning Health Systems

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Introduction: Texas Health Resources (THR), a large, nonprofit health care system based in the Dallas-Fort Worth area, has collaborated with the University of Texas Southwestern Medical Center (UTSW) to develop and operate a unique, integrated approach for Learning Health System (LHS) workforce development. This training model centers on academic health system faculty members conducting later-stage translational research within a partnering regional care delivery organization. Methods:The THR Clinical Scholars Program engages early career UTSW faculty members to conduct studies that are likely to have an impact on care delivery at the health system level. Interested candidates submit formal applications to the program. A joint committee comprised of senior research faculty from UTSW and THR clinical leadership reviews proposals with a focus on the shared LHS needs of both institutions-developing high quality research output that can be applied to enhance care delivery. A key prioritization criterion for funding is the degree to which the research addresses a question relevant to THR as a high-volume network with multiple channels for consumers to access care. The program emphasis is on supporting embedded research initiatives using health system data to generate knowledge that will improve the quality and efficiency of care for the patient populations served by the participant organizations. Results: We discuss specific strategic and tactical components of the THR Clinical Scholars Program including an overview of the academic affiliation agreement between the collaborating organizations, criteria for successful program applications, data sharing, and funding. We also share project summaries from selected clinical scholars as examples of the LHS research done in the program to date. Conclusion: This experience report provides an implementation framework for other academic health systems interested in adopting similar LHS workforce training models with community partners.

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Risk Prediction for Acute Kidney Injury in Patients Hospitalized With COVID-19

Cited by 6 publications

References 43 publications

Comparison of the Pathogenicity of SARS-CoV-2 Delta and Omicron Variants by Analyzing the Expression Patterns of Immune Response Genes in K18-hACE2 Transgenic Mice

Comparison of the Pathogenicity of SARS-CoV-2 Delta and Omicron Variants by Analyzing the Expression Patterns of Immune Response Genes in K18-hACE2 Transgenic Mice

Validation of a predictive model for hospital-acquired acute kidney injury with emergence of SARS-CoV-2 variants

The Texas Health Resources Clinical Scholars Program: Learning healthcare system workforce development through embedded translational research

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