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.
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.
Authors: Vadim Pedchenko; Olga Bondar; Agnes B Fogo; Roberto Vanacore; Paul Voziyan; A Richard Kitching; Jörgen Wieslander; Clifford Kashtan; Dorin-Bogdan Borza; Eric G Neilson; Curtis B Wilson; Billy G Hudson Journal: N Engl J Med Date: 2010-07-22 Impact factor: 91.245
Authors: Giulio Genovese; David J Friedman; Michael D Ross; Laurence Lecordier; Pierrick Uzureau; Barry I Freedman; Donald W Bowden; Carl D Langefeld; Taras K Oleksyk; Andrea L Uscinski Knob; Andrea J Bernhardy; Pamela J Hicks; George W Nelson; Benoit Vanhollebeke; Cheryl A Winkler; Jeffrey B Kopp; Etienne Pays; Martin R Pollak Journal: Science Date: 2010-07-15 Impact factor: 47.728
Authors: Meghan E Sise; Meridale V Baggett; Jo-Anne O Shepard; Jacob S Stevens; Eugene P Rhee Journal: N Engl J Med Date: 2020-05-13 Impact factor: 91.245
Authors: Ibrahim Batal; Glen S Markowitz; Waichi Wong; Rupali Avasare; Markus Y Mapara; Gerald B Appel; Vivette D D'Agati Journal: J Am Soc Nephrol Date: 2016-05-04 Impact factor: 10.121
Authors: Ani Nalbandian; Kartik Sehgal; Aakriti Gupta; Mahesh V Madhavan; Claire McGroder; Jacob S Stevens; Joshua R Cook; Anna S Nordvig; Daniel Shalev; Tejasav S Sehrawat; Neha Ahluwalia; Behnood Bikdeli; Donald Dietz; Caroline Der-Nigoghossian; Nadia Liyanage-Don; Gregg F Rosner; Elana J Bernstein; Sumit Mohan; Akinpelumi A Beckley; David S Seres; Toni K Choueiri; Nir Uriel; John C Ausiello; Domenico Accili; Daniel E Freedberg; Matthew Baldwin; Allan Schwartz; Daniel Brodie; Christine Kim Garcia; Mitchell S V Elkind; Jean M Connors; John P Bilezikian; Donald W Landry; Elaine Y Wan Journal: Nat Med Date: 2021-03-22 Impact factor: 53.440
Authors: Janis A Müller; Rüdiger Groß; Carina Conzelmann; Jana Krüger; Uta Merle; Johannes Steinhart; Tatjana Weil; Lennart Koepke; Caterina Prelli Bozzo; Clarissa Read; Giorgio Fois; Tim Eiseler; Julia Gehrmann; Joanne van Vuuren; Isabel M Wessbecher; Manfred Frick; Ivan G Costa; Markus Breunig; Beate Grüner; Lynn Peters; Michael Schuster; Stefan Liebau; Thomas Seufferlein; Steffen Stenger; Albrecht Stenzinger; Patrick E MacDonald; Frank Kirchhoff; Konstantin M J Sparrer; Paul Walther; Heiko Lickert; Thomas F E Barth; Martin Wagner; Jan Münch; Sandra Heller; Alexander Kleger Journal: Nat Metab Date: 2021-02-03
Authors: Luise Hassler; Fabiola Reyes; Matthew A Sparks; Paul Welling; Daniel Batlle Journal: Clin J Am Soc Nephrol Date: 2021-06-14 Impact factor: 8.237