Membranous nephropathy after a recent SARS-CoV-2 infection.

SARS-CoV-2 infections can induce kidney injury and glomerulopathy, with the most common pathology findings being acute tubular injury and collapsing glomerulopathy.Here we describe a rare case of membranous nephropathy in a man in his late 70s presented with nephrotic syndrome and rapidly progressive kidney dysfunction 1 month after SARS-CoV-2 infection. Phospholipase A2 receptor antibodies were positive. He was treated with rituximab, with proteinuria control. We review the cases reported in the literature.

BSG/CD147 and ACE2 Receptors Facilitate Direct SARS-CoV-2 Infection of Human iPS Cell-Derived Kidney Podocytes (preprint)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the Coronavirus disease 2019 (COVID-19), which was declared a pandemic by the World Health Organization (WHO) in March 2020. The disease has killed more than 3.8 million people worldwide. While cells in the respiratory system are the initial target for SARS-CoV-2, clinical studies suggest that COVID-19 can become a multi-organ disease in the most severe cases. Still, the direct affinity of SARS-CoV-2 for cells in other organs such as the kidneys, which are often affected in severe COVID-19, remains poorly understood. Here, we employed a human induced pluripotent stem (iPS) cell-derived model to investigate the affinity of SARS-CoV-2 for kidney glomerular podocytes. Global gene expression and qPCR analyses revealed that human iPS cell-derived podocytes express many host factor genes (including ACE2, BSG/CD147, PLS3, ACTR3, DOCK7, TMPRSS2, CTSL CD209, and CD33) associated with SARS-CoV-2 binding and viral processing. Infection of podocytes with live SARS-CoV-2 or spike-pseudotyped lentiviral particles revealed viral uptake by the cells at low Multiplicity of Infection (MOI of 0.01) as confirmed by RNA quantification and immunofluorescence studies. Our results also indicate that direct infection of human iPS cell-derived podocytes by SARS-CoV-2 virus can cause cell death and podocyte foot process retraction, a hallmark of podocytopathies and progressive glomerular diseases including collapsing glomerulopathy observed in patients with severe COVID-19 disease. Additionally, antibody blocking experiments identified BSG/CD147 and ACE2 receptors as key mediators of spike binding activity in human iPS cell-derived podocytes. These results show that SARS-CoV-2 can infect kidney glomerular podocytes in vitro, making this model potentially useful for kidney-specific antiviral drug screening and mechanistic studies of COVID-19 organotropism.Funding Information: S.M. is a recipient of the Whitehead Scholarship in Biomedical Research, a Chair’s Research Award from the Department of Medicine at Duke University, a MEDx Pilot Grant on Biomechanics in Injury or injury repair, a Burroughs Wellcome Fund PDEP Career Transition Ad Hoc Award, a Duke Incubation Fund from the Duke Innovation & Entrepreneurship Initiative, and a George O’Brien Kidney Center Pilot Grant (P30DK081943). R.B. is a recipient of the Lew’s Predoctoral Fellowship in the Center for Biomolecular and Tissue Engineering (CBTE) at Duke University (T32 Support NIH Grant T32GM800555); M.A.B. is a recipient of an NSF graduate research fellowship; and X.M. is a recipient of the graduate research fellowship from the International Foundation for Ethical Research, INC.Declaration of Interests: The authors have no conflict of interests.Ethics Approval Statement: All cell lines used for this study were obtained under appropriate material transfer agreements and approved by all involved institutional review boards.

Pathophysiology and Pathology of Acute Kidney Injury in Patients With COVID-19.

Acute kidney injury (AKI) is common among hospitalized patients with Coronavirus Infectious Disease 2019 (COVID-19), with the occurrence of AKI ranging from 0.5% to 80%. The variability in the occurrence of AKI has been attributed to the difference in geographic locations, race/ethnicity, and severity of illness. AKI among hospitalized patients is associated with increased length of stay and in-hospital deaths. Even patients with AKI who survive to hospital discharge are at risk of developing chronic kidney disease or end-stage kidney disease. An improved knowledge of the pathophysiology of AKI in COVID-19 is crucial to mitigate and manage AKI and to improve the survival of patients who developed AKI during COVID-19. The goal of this article is to provide our current understanding of the etiology and the pathophysiology of AKI in the setting of COVID-19.

COVID-19 infection in a membranous nephropathy patient treated with rituximab.

While COVID-19 pandemic continues to affect our country and most countries in the world, we have to make some changes both in our social life and our approach to healthcare. We have to struggle with the pandemic on one hand and also try to follow up and treat our patients with chronic diseases in the most appropriate way. In this period, one of our group of patients who are challenging us for follow-up and treatment are those who should start or continue to use immunosuppressive therapy. In order to contribute to the accumulation of knowledge in this area, we wanted to report a patient who was followed up with the diagnosis of COVID-19 and had been administered rituximab very recently due to a nephrotic syndrome caused by membranous nephropathy.

COVID-19-Related Collapsing Glomerulopathy in a Kidney Transplant Recipient.

We report a case of a kidney transplant recipient who presented with acute kidney injury and nephrotic-range proteinuria in a context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Kidney biopsy revealed collapsing glomerulopathy. Droplet-based digital polymerase chain reaction did not detect the presence of SARS-CoV-2 RNA in the biopsy fragment, and the virus was barely detectable in plasma at the time of the biopsy. SARS-CoV-2 RNAemia peaked several days later, followed by a seroconversion despite the absence of circulating CD19-positive lymphocytes at admission due to rituximab-based treatment of antibody-mediated rejection 3 months earlier. Genotyping for the 2 risk alleles of the apolipoprotein L1 (APOL1) gene revealed that the donor carried the low-risk G0/G2 genotype. This case illustrates that coronavirus disease 2019 infection may promote a collapsing glomerulopathy in kidney allografts with a low-risk APOL1 genotype in the absence of detectable SARS-CoV-2 RNA in the kidney and that podocyte injury may precede SARS-CoV-2 RNAemia.