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Heterogenous Renal Injury Biomarker Production Reveals Human Sepsis-Associated Acute Kidney Injury Subtypes
Daniela Jou-Valencia1,2, Jacqueline Koeze1, Eliane R Popa2
1Department of Critical Care, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Critical Care Explorations
|March 14, 2020
Summary
Sepsis-acute kidney injury involves diverse pathways, as indicated by varying levels of neutrophil gelatinase-associated lipocalin and kidney injury molecule-1. Identifying these distinct pathophysiological features may enable sepsis-acute kidney injury patient subtyping.
Area of Science:
- Nephrology
- Critical Care Medicine
- Molecular Biology
Background:
- Sepsis-acute kidney injury (AKI) is a complex condition with poorly understood mechanisms.
- Biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) are crucial for assessing renal injury.
Purpose of the Study:
- To investigate the expression patterns of NGAL and KIM-1 in renal biopsies from sepsis-AKI patients.
- To explore whether these expression levels can help identify distinct pathophysiological subtypes of sepsis-AKI.
Main Methods:
- A prospective clinical laboratory study utilized postmortem kidney biopsies from adult sepsis-AKI patients and control subjects.
- Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemical staining quantified NGAL and KIM-1 mRNA and protein levels.
- Morphometric analysis and laser microdissection were employed to assess biomarker localization and glomerular production.
Main Results:
- NGAL and KIM-1 mRNA and protein levels were significantly elevated in sepsis-AKI kidneys compared to controls.
- NGAL localized to distal tubules and arterioles, while KIM-1 was found in proximal tubules, with no correlation between their levels.
- Biomarker levels did not correlate with the extent of renal injury, illness severity, or serum creatinine, but heterogeneous glomerular NGAL production was observed.
Conclusions:
- Expression differences of NGAL and KIM-1 suggest that sepsis-AKI does not result from a single pathophysiological pathway.
- Multiple distinct pathways likely contribute to the development of sepsis-AKI.
- Patients meeting sepsis-AKI criteria may be classifiable into subtypes based on underlying pathophysiological features.
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