Autopsies conducted on 42 patients who died with coronavirus disease 2019 (COVID-19) revealed acute tubular injury (ATI) as the main pathologic finding correlating with acute kidney injury (AKI) in this cohort. The results were published in the Journal of the American Society of Nephrology.
Researchers led by Dominick Santoriello, Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, noted that the “relatively mild degree of ATI, even in the setting of severe AKI, suggests that with resolution of SARS-CoV-2 infection, there is potential for renal functional recovery.”
The authors said current knowledge regarding the underlying pathology of COVID-19–associated AKI is limited, and they highlighted a recent autopsy series from China that described features of ATI in all 26 deceased COVID-19 patients, 85% of whom were graded as at least moderate, despite only nine of them showing clinical evidence of kidney injury.
The latest study looked at clinical and kidney pathology findings in 42 autopsies on patients who died with COVID-19 at Columbia University Irving Medical Center. The cohort had a median age of 71.5 years (range, 38–97 years); 69% were men, 57% were Hispanic, and 73% had a history of hypertension.
The cause of death in 30 of the 42 autopsies was respiratory failure resulting from COVID-19 pneumonia with diffuse alveolar damage and in a few cases, superimposed bacterial pneumonia. Three additional patients died from decompensated heart failure, three died from acute pulmonary emboli, two died from intracranial hemorrhage, and one died from myocardial infarction.
Assessment of serum creatinine was not available for nine individuals. Among patients with available data, AKI had developed in 31 of 33 patients (94%), including six with AKI stage 1, nine with stage 2, and 16 with stage 3. Eight patients with AKI stage 3 received continuous renal replacement therapy.
In addition, 29 patients (69%) were exposed to at least one potential nephrotoxin during hospitalization, and 29% were exposed to two or more, the most frequent being vancomycin, which was administered to 28 patients. IL-6, C-reactive protein, D-dimer levels and fibrinogen activity were significantly elevated in nearly all patients.
For each patient, coronal sections of both kidneys containing >200 glomeruli were evaluated. The authors said glomeruli were well preserved in the majority of kidneys. Despite a median age of 71.5 years and a high incidence of hypertension (73.2%), ≤25% of glomeruli were globally sclerotic in 34 of 42 autopsies (81%). In the remaining eight patients, renal parenchymal scarring was mostly due to hypertensive arterionephrosclerosis and/or nodular diabetic glomerulosclerosis (NDGS).
Meanwhile, glomeruli exhibited no more than mild, nonspecific changes, such as enlargement, mild mesangial sclerosis, and focal ischemic-type wrinkling of the glomerular basement membrane, in 29 of 42 autopsies (69%). Seven autopsies exhibited findings of diabetic glomerulosclerosis (mainly NDGS), and one each displayed collapsing focal segmental glomerulosclerosis (FSGS), idiopathic nodular glomerulosclerosis, and IgA nephropathy (IgAN; in the setting of chronic liver disease).
Fibrin thrombi were identified in the kidneys in six autopsies and were distributed in glomeruli, in arteries or arterioles, or in both glomeruli and arterioles. In two of six autopsies with fibrin thrombi, focal microinfarction was noted, measuring approximately 3 and 10 mm. However, renal fibrin thrombi were focal in all autopsies; when present, <5% of glomeruli contained thrombi.
Although 11 autopsies could not be assessed for ATI due to autolysis, in the remaining 31, ATI was graded as absent or minimal in 12 (39%), mild in 12 (39%), or moderate-to-severe in 7 (23%). “Not surprisingly, ATI was less evident in AKI stage 1. Somewhat surprisingly, even in the presence of AKI stage 2 or 3, tubular injury was graded as moderate-to-severe in only 5 of 17 autopsies (29%), and it was largely absent in 2,” the authors said, and “as such, the most distinctive finding was relatively profound elevation in serum creatinine (AKI stage 2 or 3) associated with no more than mild ATI in the majority of cases.”
“The finding of only mild ATI in the setting of severe creatinine elevation suggests a pathogenesis involving tubular injury and hemodynamic factors (such as aggressive fluid management) and potential for recovery of renal function upon resolution of infection,” they said, adding that results point to a “complex etiology that likely involves ischemia, hypoxia, sepsis-associated factors, and toxin exposure. Equally notable is the absence of findings of classic viral nephropathy, diffuse thrombotic microangiopathy, or acute glomerulonephritis.”
The authors highlighted the fact that they did not have data to compare the initial 42 COVID-19 patients who underwent autopsy with the significantly larger number of patients who died at New York–Presbyterian/Columbia University Irving Medical Center with COVID-19 during the pandemic, or even the larger number of patients who recovered. As a result, they said it is unclear how generalizable their findings are. They also noted that tissue evaluation was limited due to autolysis related to prolonged post-mortem interval.