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Peripheral Transcriptomics in Acute and Long-Term Kidney Dysfunction in SARS-CoV2 Infection.
Medrxiv : the Preprint Server for Health Sciences
|November 14, 2023
Summary
Acute kidney injury (AKI) in COVID-19 patients involves mitochondrial dysfunction and ER stress. Long-term kidney dysfunction is linked to cardiac issues and immune dysregulation, with shared pathways to sepsis-AKI.
Area of Science:
- Nephrology
- Genomics
- Infectious Diseases
Background:
- Acute kidney injury (AKI) is a common complication in hospitalized SARS-CoV2 patients, potentially leading to chronic kidney disease.
- Peripheral blood molecular signatures associated with COVID-19 AKI and their impact on long-term kidney function remain largely uncharacterized.
Approach:
- Bulk RNA sequencing was performed on peripheral blood mononuclear cells (PBMCs) from 283 hospitalized SARS-CoV2 patients.
- Differential gene expression analysis identified molecular signatures in AKI, which were compared to sepsis-AKI cohorts.
- Associations between identified gene expression signatures and long-term kidney function (eGFR) were evaluated.
Key Points:
- 2635 significant differential gene expressions were identified in COVID-19 AKI patients (FDR<0.05), with top pathways including EIF2 signaling, oxidative phosphorylation, mTOR signaling, and Th17 signaling.
- Mitochondrial dysfunction and endoplasmic reticulum (ER) stress were indicated as key mechanisms in acute COVID-19 AKI.
- A significant overlap (48.14%) in key pathways was observed between COVID-19 AKI and sepsis-associated AKI.
- 164 genes (6.2%) were associated with decreased long-term kidney function, notably related to autophagy, renal fibrosis, and cardiac structure/function.
Conclusions:
- COVID-19 AKI is a multifactorial condition driven by ER stress-induced mitochondrial dysfunction.
- Long-term kidney function decline post-COVID-19 AKI is associated with cardiac factors and immune dysregulation.
- Shared molecular signatures with sepsis-AKI suggest potential for therapeutic repurposing and generalizable treatment strategies.
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