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.
Highlights
The recent COVID-19 pandemic has resulted in major morbidity and mortality
Patient characteristics Postmortem biopsies were collected from patients that died in the intensive care unit (ICU) with organ failure related to either COVID-19 or bacterial sepsis
We found low renal ACE2 Messenger RNA (mRNA) levels in both COVID-19 and bacterial sepsis patients compared to control, whereas the mRNA levels of CD147 remained unaltered in renal tissue from COVID-19 and bacterial sepsis patients compared to control (Fig. 3)
Summary
The recent COVID-19 pandemic has resulted in major morbidity and mortality. The number of ICU-admitted COVID-19 patients developing AKI (COVID-AKI) varies per geographical area but has been reported to be as high as 20–76% [1,2,3,4] and is associated with poor prognosis [5]. The mortality of critically ill COVID-19 patients requiring renal replacement therapy (RRT) varies between 42 and 90% [4, 6, 7]. Recent autopsy studies have provided information on the consequences of SARS-CoV-2 infection on kidney histopathology, the mechanisms driving renal failure remain poorly understood and treatment strategies aiming to limit or reverse renal failure are still lacking. Previous reports have suggested that the renal pathophysiology associated with COVID-19 is similar to that described for patients with bacterial sepsis [8, 9]. The mechanisms driving acute kidney injury (AKI) in critically ill COVID-19 patients are unclear. We col‐ lected 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
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