Comparison of renal histopathology and gene expression profiles between severe COVID-19 and bacterial sepsis in critically ill patients.

Abstract

BACKGROUND:

The mechanisms driving acute kidney injury (AKI) in critically ill COVID-19 patients are unclear. We collected kidney biopsies from COVID-19 AKI patients within 30 min after death in order to examine the histopathology and perform mRNA expression analysis of genes associated with renal injury.

METHODS:

This study involved histopathology and mRNA analyses of postmortem kidney biopsies collected from patients with COVID-19 (n = 6) and bacterial sepsis (n = 27). Normal control renal tissue was obtained from patients undergoing total nephrectomy (n = 12). The mean length of ICU admission-to-biopsy was 30 days for COVID-19 and 3-4 days for bacterial sepsis patients.

RESULTS:

We did not detect SARS-CoV-2 RNA in kidney biopsies from COVID-19-AKI patients yet lung tissue from the same patients was PCR positive. Extensive acute tubular necrosis (ATN) and peritubular thrombi were distinct histopathology features of COVID-19-AKI compared to bacterial sepsis-AKI. ACE2 mRNA levels in both COVID-19 (fold change 0.42, p = 0.0002) and bacterial sepsis patients (fold change 0.24, p < 0.0001) were low compared to control. The mRNA levels of injury markers NGAL and KIM-1 were unaltered compared to control tissue but increased in sepsis-AKI patients. Markers for inflammation and endothelial activation were unaltered in COVID-19 suggesting a lack of renal inflammation. Renal mRNA levels of endothelial integrity markers CD31, PV-1 and VE-Cadherin did not differ from control individuals yet were increased in bacterial sepsis patients (CD31 fold change 2.3, p = 0.0006, PV-1 fold change 1.5, p = 0.008). Angiopoietin-1 mRNA levels were downregulated in renal tissue from both COVID-19 (fold change 0.27, p < 0.0001) and bacterial sepsis patients (fold change 0.67, p < 0.0001) compared to controls. Moreover, low Tie2 mRNA expression (fold change 0.33, p = 0.037) and a disturbed VEGFR2/VEGFR3 ratio (fold change 0.09, p < 0.0001) suggest decreased microvascular flow in COVID-19.

CONCLUSIONS:

In a small cohort of postmortem kidney biopsies from COVID-19 patients, we observed distinct histopathological and gene expression profiles between COVID-19-AKI and bacterial sepsis-AKI. COVID-19 was associated with more severe ATN and microvascular thrombosis coupled with decreased microvascular flow, yet minimal inflammation. Further studies are required to determine whether these observations are a result of true pathophysiological differences or related to the timing of biopsy after disease onset.

• Authors: Meint Volbeda, Daniela Jou-Valencia, Marius C van den Heuvel, Marjolein Knoester, Peter J Zwiers, Janesh Pillay, Stefan P Berger, Peter H J van der Voort, Jan G Zijlstra, Matijs van Meurs, Jill Moser
• Journal: Critical care (London, England) (Crit Care) Vol. 25 Issue 1 Pg. 202 (06 10 2021) ISSN: 1466-609X [Electronic] England
• PMID: 34112226 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Acute Kidney Injury (etiology, physiopathology)
• Adult
• Aged
• Aged, 80 and over
• Analysis of Variance
• COVID-19 (genetics, pathology, physiopathology)
• Critical Illness (therapy)
• Female
• Gene Expression (genetics)
• Humans
• Intensive Care Units (organization & administration, statistics & numerical data)
• Kidney (pathology, physiopathology)
• Male
• Middle Aged
• Sepsis (genetics, pathology, physiopathology)
• Simplified Acute Physiology Score