A multi-center retrospective cohort study defines the spectrum of kidney pathology in Coronavirus 2019 Disease (COVID-19)
Authors: Rebecca M. May, Clarissa Cassol, Andrew Hannoudi, Christopher P. Larsen, Edgar V. Lerma, Randy S. Haun, Juarez R. Braga, Samar I. Hassen, Jon Wilson, Christine VanBeek, Mahesha Vankalakunti, Lilli Barnum, Patrick D. Walker, T. David Bourne, Nidia C. Messias, Josephine M. Ambruzs, Christie L. Boils, Shree S. Sharma, L. Nicholas Cossey, Pravir V. Baxi, Matthew Palmer, Jonathan E. Zuckerman, Vighnesh Walavalkar, Anatoly Urisman, Alexander J. Gallan, Laith F. Al-Rabadi, Roger Rodby, Valerie Luyckx, Gustavo Espino, Srivilliputtur Santhana-Krishnan, Brent Alper, Son G. Lam, Ghadeer N. Hannoudi, Dwight Matthew, Mark Belz, Gary Singer, Srikanth Kunaparaju, Deborah Price, Saurabh Chawla, Chetana Rondla, Mazen A. Abdalla, Marcus L. Britton, Subir Paul, Uday Ranjit, Prasad Bichu, Sean R. Williamson, Yuvraj Sharma, Ariana Gaspert, Philipp Grosse, Ian Meyer, Brahm Vasudev, Mohamad El Kassem, Juan Carlos Q. Velez, Tiffany N. Caza
Journal: Kidney International (2021)

Kidney failure is common in patients with Coronavirus Disease-19 (COVID-19), resulting in increased morbidity and mortality. In an international collaboration, 284 kidney biopsies were evaluated to improve understanding of kidney disease in COVID-19. Diagnoses were compared to five years of 63,575 native biopsies prior to the pandemic and 13,955 allograft biopsies to identify diseases that have increased in patients with COVID-19. Genotyping for APOL1 G1 and G2 alleles was performed in 107 African American and Hispanic patients. Immunohistochemistry for SARS-CoV-2 was utilized to assess direct viral infection in 273 cases along with clinical information at the time of biopsy. The leading indication for native biopsy was acute kidney injury (45.4%), followed by proteinuria with or without concurrent acute kidney injury (42.6%). There were more African American patients (44.6%) than patients of other ethnicities. The most common diagnosis in native biopsies was collapsing glomerulopathy (25.8%), which was associated with high-risk APOL1 genotypes in 91.7% of cases. Compared to the five-year biopsy database, the frequency of myoglobin cast nephropathy and proliferative glomerulonephritis with monoclonal IgG deposits was also increased in patients with COVID-19 (3.3% and 1.7%, respectively), while there was a reduced frequency of chronic conditions (including diabetes mellitus, IgA nephropathy, and arterionephrosclerosis) as the primary diagnosis. In transplants, the leading indication was acute kidney injury (86.4%), for which rejection was the predominant diagnosis (61.4%). Direct SARS-CoV-2 viral infection was not identified. Thus, our multi-center large case series identified kidney diseases that disproportionately affect patients with COVID-19 and demonstrated a high frequency of APOL1 high-risk genotypes within this group, with no evidence of direct viral infection within the kidney. Kidney failure is common in patients with Coronavirus Disease-19 (COVID-19), resulting in increased morbidity and mortality. In an international collaboration, 284 kidney biopsies were evaluated to improve understanding of kidney disease in COVID-19. Diagnoses were compared to five years of 63,575 native biopsies prior to the pandemic and 13,955 allograft biopsies to identify diseases that have increased in patients with COVID-19. Genotyping for APOL1 G1 and G2 alleles was performed in 107 African American and Hispanic patients. Immunohistochemistry for SARS-CoV-2 was utilized to assess direct viral infection in 273 cases along with clinical information at the time of biopsy. The leading indication for native biopsy was acute kidney injury (45.4%), followed by proteinuria with or without concurrent acute kidney injury (42.6%). There were more African American patients (44.6%) than patients of other ethnicities. The most common diagnosis in native biopsies was collapsing glomerulopathy (25.8%), which was associated with high-risk APOL1 genotypes in 91.7% of cases. Compared to the five-year biopsy database, the frequency of myoglobin cast nephropathy and proliferative glomerulonephritis with monoclonal IgG deposits was also increased in patients with COVID-19 (3.3% and 1.7%, respectively), while there was a reduced frequency of chronic conditions (including diabetes mellitus, IgA nephropathy, and arterionephrosclerosis) as the primary diagnosis. In transplants, the leading indication was acute kidney injury (86.4%), for which rejection was the predominant diagnosis (61.4%). Direct SARS-CoV-2 viral infection was not identified. Thus, our multi-center large case series identified kidney diseases that disproportionately affect patients with COVID-19 and demonstrated a high frequency of APOL1 high-risk genotypes within this group, with no evidence of direct viral infection within the kidney. 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These studies have been useful in elucidating the need for kidney biopsy in COVID-19 patients for proper diagnosis and disease management. However, given the large spectrum of diagnoses, it is unclear from small series and case reports which diseases are enriched in COVID-19 patients. Additionally, single-case reports can be subject to publication bias, with those reporting interesting or unusual clinical presentations more likely to be published. We present the largest kidney biopsy series to date, encompassing 240 native and 44 allograft biopsies in an international collaborative effort to improve our understanding of kidney disease in COVID-19. We sought to determine which kidney diseases are enriched in patients with COVID-19 through comparison of this series to a pre–COVID-19 biopsy cohort. A multi-center clinicopathologic study of kidney pathology in COVID-19 patients was initiated following approval by the Solutions Institutional Review Board, with adherence to the principles of the Declaration of Helsinki. Multiple kidney pathologists and nephrologists were invited to participate and together comprised the COVID-19 Kidney Biopsy Consortium. Biopsies were received from a total of 9 institutions, from the United States, Switzerland, and India. The participating centers included the University of California, Los Angeles (n = 2), the University of California, San Francisco (n = 2), the University of Pennsylvania (n = 2), Medical College of Wisconsin (n = 1), Rush University (n = 2), Ameripath Laboratories (n = 7), the University of Utah (n = 2), the University of Zurich (Switzerland, n = 1), and Manipal Hospital (Bangalore, India, n = 13); the remaining cases were from Arkana Laboratories, which received them from multiple nephrology practices among several states (n = 252). Cases