by 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 Jill Moser
Critical Care volume 25,
Article number: 202 (2021)
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.