Evidence map›Paper›PMID 34112226›Full record

ArticleCritical care (London, England)2021

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

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 and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Critical care (London, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
3.9field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 30 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Meint VolbedaDepartment of Critical Care, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Daniela Jou-ValenciaDepartment of Critical Care, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Marius C van den HeuvelDepartment of Pathology and Medical Biology, Pathology Section, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Marjolein KnoesterDepartment of Clinical Microbiology and Infection Prevention, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Peter J ZwiersDepartment of Pathology and Medical Biology, Medical Biology Section, Laboratory for Endothelial Biomedicine and Vascular Drug Targeting Research, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Janesh PillayDepartment of Critical Care, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Stefan P BergerDepartment of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Peter H J van der VoortDepartment of Critical Care, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Jan G ZijlstraDepartment of Critical Care, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Matijs van MeursDepartment of Critical Care, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Jill MoserDepartment of Critical Care, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands. j.moser@umcg.nl.ORCID 0000-0002-9614-2577
University Medical Center Groningen · NL

Funding

ZonMw 10430012010006
6 · The paper itself

Abstract

backgroundThe 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.

methodsThis 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.

resultsWe 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.

conclusionsIn 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.

Indexed as

Acute Kidney InjuryAdultAgedAged, 80 and overAnalysis of VarianceCOVID-19Critical IllnessFemaleGene ExpressionHumansIntensive Care UnitsKidneyMaleMiddle AgedSepsisSimplified Acute Physiology ScoreAcute kidney injuryBacterial sepsisCOVID-19

Identifiers

PMID34112226
PMCPMC8190989
OpenAlexW3169640707

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.