Kidney pathology findings in patients dying with COVID-19

ABSTRACT

Background: The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leading to coronavirus disease 2019 (COVID-19) has predominantly resulted in a profound hypoxic respiratory disease with a significant subset of patients demonstrating abnormalities in renal function. Acute kidney injury (AKI) in these patients is an independent risk factor for mortality;however, the mechanism for injury is unknown and our understanding of the pathologic findings is limited. Methods: Kidney tissue from nine patients who died with COVID-19 was obtained at autopsy and evaluated by light, immunofluorescence, and electron microscopy. RNAScope technology was used to perform RNA in situ hybridization (RNA ISH) with probes to the SARS-CoV-2 virus (sense) and for human gene ACE2. Results: The cohort was comprised of 6 men and 3 women, 78% black, median age of 65 years (37 - 78) and median body mass index 29 (26 - 48) kg/m2, of which 6 (67%) had hypertension and 4 (44%) had diabetes. AKI was present in 7 of 9 (78%), 5 (55%) of them needed dialysis. One patient had creatine kinase about 5000 U/L suggestive of rhabdomyolysis. All but one expired while on mechanical ventilation. The predominant morphologic finding on postmortem biopsy was acute tubular injury. Three cases (33%) demonstrated endocapillary platelet aggregates with one demonstrating fibrin tactoids and loss of endothelial fenestrations by EM, consistent with early TMA;however, no overt thrombotic microangiopathy was present. Immunofluorescence in one case demonstrated mesangial C3 staining without deposits by EM. Background mild-to-moderate arterionephrosclerosis was present in 6 of 9 (67%) cases. In one patient with AKI at time of death, RNA-ISH detected SARS-CoV-2 in tubular epithelial cells which also express ACE2, the receptor for coronavirus cell entry. Conclusions: Among a cohort of 9 patients dying with COVID-19, postmortem evaluation of kidney samples predominantly revealed ATI without overt evidence of hypercoaguloability, complement dysregulation, or immune complex deposition. While the mechanism for AKI in most cases is not immediately apparent, this series suggests, but does not prove, direct renal infection with SARS-CoV-2 as the presence of viral RNA does not prove active viral infection.