COVID-19–Associated Glomerular Disease
Authors: Shetty Aneesha A. , Tawhari Ibrahim , Safar-Boueri Luisa , Seif Nay , Alahmadi Ameen , Gargiulo Richard , Aggarwal Vikram , Usman Irtaza , Kisselev Sergey , Gharavi Ali G. , Kanwar Yahspal , Quaggin Susan E. 
Published: November 2020

Significance Statement
Studies have found AKI with high-grade proteinuria in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this patient series, the authors describe six patients of recent African ancestry who developed COVID-19–associated AKI with podocytopathy, collapsing glomerulopathy, or both. Respiratory symptoms among these patients were generally mild, and none required ventilator support. Previous research has demonstrated an association between high-risk gene variants in the APOL1 gene, which encodes the APOL1 protein, and collapsing glomerulopathy in patients with another viral infection, HIV. Genetic testing in three of the patients in this study confirmed that they had high-risk APOL1 genotypes. In one of these patients, collapsing glomerulopathy occurred in the engrafted kidney, which was transplanted from a donor who carried an APOL1 low-risk genotype, a finding inconsistent with current models of APOL1-mediated kidney injury.

Background
Studies have documented AKI with high-grade proteinuria in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In some patients, biopsies have revealed collapsing glomerulopathy, a distinct form of glomerular injury that has been associated with other viruses, including HIV. Previous patient reports have described patients of African ancestry who developed nephrotic-range proteinuria and AKI early in the course of disease.

Methods
In this patient series, we identified six patients with coronavirus disease 2019 (COVID-19), AKI, and nephrotic-range proteinuria. COVID-19 was diagnosed by a positive nasopharyngeal swab RT-PCR for SARS-CoV-2 infection. We examined biopsy specimens from one transplanted kidney and five native kidneys. Three of the six patients underwent genetic analysis of APOL1, the gene encoding the APOL1 protein, from DNA extracted from peripheral blood. In addition, we purified genomic DNA from paraffin-embedded tissue and performed APOL1 genotype analysis of one of the native biopsies and the donor kidney graft.

Results
All six patients were of recent African ancestry. They developed COVID-19–associated AKI with podocytopathy, collapsing glomerulopathy, or both. Patients exhibited generally mild respiratory symptoms, and no patient required ventilator support. Genetic testing performed in three patients confirmed high-risk APOL1 genotypes. One APOL1 high-risk patient developed collapsing glomerulopathy in the engrafted kidney, which was transplanted from a donor who carried a low-risk APOL1 genotype; this contradicts current models of APOL1-mediated kidney injury, and suggests that intrinsic renal expression of APOL1 may not be the driver of nephrotoxicity and specifically, of podocyte injury.

Conclusions
Glomerular disease presenting as proteinuria with or without AKI is an important presentation of COVID-19 infection and may be associated with a high-risk APOL1 genotype.