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Acute Kidney Injury-Induced Circulating TNFR1/2 Elevations Correlate with Persistent Kidney Injury and Progression to
Akshayakeerthi Arthanarisami1, Yohei Komaru1, Charikleia Katsouridi1
1Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA.
Cells
|September 28, 2023
Summary
Acute kidney injury (AKI) rapidly elevates circulating tumor necrosis factor receptors 1 and 2 (cTNFR1/2). These elevations reflect loss of kidney function and predict chronic kidney disease progression and fibrosis.
Area of Science:
- Nephrology
- Immunology
- Biomarker Discovery
Background:
- Elevated circulating tumor necrosis factor receptors 1 and 2 (cTNFR1/2) predict chronic kidney disease (CKD) progression.
- Mechanisms of TNFR1/2 release and their role in acute kidney injury (AKI) remain unclear.
Purpose of the Study:
- To investigate whether AKI drives cTNFR1/2 elevations.
- To determine if cTNFR1/2 levels predict outcomes after AKI.
- To elucidate the source and significance of cTNFR1/2 in kidney injury.
Main Methods:
- Analysis of serum and urine from AKI patients and mouse models of kidney injury (ischemic, obstructive, toxic).
- Assessment of kidney tissue expression and correlation with fibrosis, nephrectomy, and single-cell RNA-sequencing data.
- Evaluation of uremic toxin effects and TNF neutralization.
Main Results:
- TNFR1/2 levels were significantly elevated in serum and urine within one hour post-AKI in mice and patients, correlating with injury severity.
- Bilateral nephrectomies caused substantial cTNFR1/2 elevations, suggesting extrarenal sources.
- Elevated cTNFR1/2 levels after AKI did not reflect TNF activity but rather loss of kidney function and uremia.
- Sustained cTNFR1/2 elevations correlated with persistent kidney injury and fibrosis during the AKI-to-CKD transition.
Conclusions:
- Kidney injury acutely increases cTNFR1/2 serum levels, inversely correlating with kidney function.
- Sustained cTNFR1/2 elevations post-AKI indicate ongoing tissue damage and progression to fibrosis.
- cTNFR1/2 serve as potential biomarkers for AKI severity and CKD progression.
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