Kidney Biopsy Findings in Patients with COVID-19

<jats:sec> <jats:title>Significance Statement</jats:title> <jats:p>The mechanisms underlying coronavirus disease 2019 (COVID-19)–associated kidney injury are unknown, and morphologic correlates are few and limited to patient reports or autopsy series. The authors’ evaluation of a biopsy series of 14 native and 3 allograft kidneys from patients with COVID-19 who developed AKI or nephrotic-range proteinuria found diverse glomerular and tubular diseases. These included collapsing glomerulopathy and minimal change disease (both of which occurred in patients with high-risk <jats:italic toggle="yes">APOL1</jats:italic> gene variants), membranous glomerulopathy, anti-GBM nephritis, acute tubular injury, exacerbation of preexisting autoimmune GN, and allograft rejection. They found no definitive evidence of SARS-CoV-2 in the samples by <jats:italic toggle="yes">in situ</jats:italic> hybridization, immunohistochemistry and electron microscopy, arguing against direct viral infection of the kidney as the major pathomechanism. Instead, the findings implicate cytokine-mediated effects and heightened adaptive immune responses. The kidney biopsy findings informed treatment and prognosis.</jats:p> </jats:sec> <jats:sec> <jats:title>Background</jats:title> <jats:p>Coronavirus disease 2019 (COVID-19) is thought to cause kidney injury by a variety of mechanisms. To date, pathologic analyses have been limited to patient reports and autopsy series.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>We evaluated biopsy samples of native and allograft kidneys from patients with COVID-19 at a single center in New York City between March and June of 2020. We also used immunohistochemistry, <jats:italic toggle="yes">in situ</jats:italic> hybridization, and electron microscopy to examine this tissue for presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>The study group included 17 patients with COVID-19 (12 men, 12 black; median age of 54 years). Sixteen patients had comorbidities, including hypertension, obesity, diabetes, malignancy, or a kidney or heart allograft. Nine patients developed COVID-19 pneumonia. Fifteen patients (88%) presented with AKI; nine had nephrotic-range proteinuria. Among 14 patients with a native kidney biopsy, 5 were diagnosed with collapsing glomerulopathy, 1 was diagnosed with minimal change disease, 2 were diagnosed with membranous glomerulopathy, 1 was diagnosed with crescentic transformation of lupus nephritis, 1 was diagnosed with anti-GBM nephritis, and 4 were diagnosed with isolated acute tubular injury. The three allograft specimens showed grade 2A acute T cell–mediated rejection, cortical infarction, or acute tubular injury. Genotyping of three patients with collapsing glomerulopathy and the patient with minimal change disease revealed that all four patients had <jats:italic toggle="yes">APOL1</jats:italic> high-risk gene variants. We found no definitive evidence of SARS-CoV-2 in kidney cells. Biopsy diagnosis informed treatment and prognosis in all patients.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Patients with COVID-19 develop a wide spectrum of glomerular and tubular diseases. Our findings provide evidence against direct viral infection of the kidneys as the major pathomechanism for COVID-19–related kidney injury and implicate cytokine-mediated effects and heightened adaptive immune responses.</jats:p> </jats:sec>