Kidney Biopsy Findings in Patients with COVID-19
Authors: Satoru Kudose, Ibrahim Batal, Dominick Santoriello, Katherine Xu, Jonathan Barasch, Yonatan Peleg, Pietro Canetta, Lloyd E. Ratner, Maddalena Marasa, Ali G. Gharavi, M. Barry Stokes, Glen S. Markowitz, Vivette D. D’Agati
Journal: Journal of the American Society of Nephrology (2020)

Significance Statement 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 APOL1 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 in situ 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. Background 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. Methods 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, in situ hybridization, and electron microscopy to examine this tissue for presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results 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 APOL1 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. Conclusions 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.