Collapsing Focal Segmental Glomerulosclerosis in Viral Infections

Abstract

Collapsing glomerulopathy represents a special variant of the proteinuric kidney disease focal segmental glomerulosclerosis (FSGS). Histologically, the collapsing form of FSGS (cFSGS) is characterized by segmental or global condensation and obliteration of glomerular capillaries, the appearance of hyperplastic and hypertrophic podocytes and severe tubulointerstitial damage. Clinically, cFSGS patients present with acute kidney injury, nephrotic-range proteinuria and are at a high risk of rapid progression to irreversible kidney failure. cFSGS can be attributed to numerous etiologies, namely, viral infections like HIV, cytomegalovirus, Epstein–Barr-Virus, and parvovirus B19 and also drugs and severe ischemia. Risk variants of the APOL1 gene, predominantly found in people of African descent, increase the risk of developing cFSGS. Patients infected with the new Corona-Virus SARS-CoV-2 display an increased rate of acute kidney injury (AKI) in severe cases of COVID-19. Besides hemodynamic instability, cytokine mediated injury and direct viral entry and infection of renal epithelial cells contributing to AKI, there are emerging reports of cFSGS associated with SARS-CoV-2 infection in patients of mainly African ethnicity. The pathogenesis of cFSGS is proposed to be linked with direct viral infection of podocytes, as described for HIV-associated glomerulopathy. Nevertheless, there is growing evidence that the systemic inflammatory cascade, activated in acute viral infections like COVID-19, is a major contributor to the impairment of basic cellular functions in podocytes. This mini review will summarize the current knowledge on cFSGS associated with viral infections with a special focus on the influence of systemic immune responses and potential mechanisms propagating the development of cFSGS.

The Pathology Lesion Patterns of Podocytopathies: How and why?

“…Afterwards, terminology has evolved in collapsing glomerulopathy to underline the rapid and catastrophic collapsing nature of the pathological process. CG is histologically defined by the formation of a pseudocrescent, i.e., a massive proliferation of cuboidal undifferentiated epithelial cell in the Bowman space, leading to a collapse of the capillary loops, regardless of the extracellular matrix accumulation eventually leading to focal and global glomerulosclerosis ( Muehlig et al, 2021 ) ( Figure 1 ). This pattern of injury represents a common endpoint from multiple etiologies (APOL1 risk variants, infections, drugs, ischemia, hematologic neoplasia and autoimmune disease), suggesting a common pathological mechanism rather than a specific cause ( Nicholas Cossey et al, 2017 ).…”

“…A typical clinical condition associated with collapsing pattern of injury at kidney biopsy is viral-mediated nephropathy, such as that observed with HIV, Parvovirus and SARS-CoV-2 infection ( Muehlig et al, 2021 ). Pseudocrescents, collapse of the capillary loops and podocyte multinucleation are predominant features of HIV-associated nephropathy ( Barisoni et al, 2000 ; Suzuki et al, 2009 ; Lasagni et al, 2013 ; Liapis et al, 2013 ; Al Hussain et al, 2017 ).…”

ScoMorphoFISH: A deep learning enabled toolbox for single‐cell single‐mRNA quantification and correlative (ultra‐)morphometry

“…Further, we found that although not expressed under healthy baseline conditions, we show that the SARS‐CoV‐2 target ACE2 can be locally upregulated in damaged podocytes. As collapsing FSGS, a disease entity frequently associated with viral infections was also described in COVID‐19, 28 we apply the developed workflow to investigate the localization of SARS‐CoV‐2 RNA in a kidney biopsy of a patient suffering of a likely COVID‐19‐associated collapsing FSGS. Herein, we found that the main SARS‐CoV‐2 target were ACE2‐positive proximal tubule cells.…”

“…The barriers to establishing this method in other settings are low as only commercially available reagents are used, high-quality imaging systems are widely available, data analysis is performed in the open-source image analysis platform Fiji and the source code and pretrained DL networks are fully available.Further, we found that although not expressed under healthy baseline conditions, we show that the SARS-CoV-2 target ACE2 can be locally upregulated in damaged podocytes. As collapsing FSGS, a disease entity frequently associated with viral infections was also described in COVID-19,28 we apply the developed workflow to investigate the localization of SARS-CoV-2 RNA in a kidney biopsy of a patient suffering of a likely COVID-19-associated collapsing FSGS. Herein, we found that the main SARS-CoV-2 target were ACE2-positive proximal tubule cells.…”

Traditional Chinese Medicine in Treating Primary Podocytosis: From Fundamental Science to Clinical Research

“…Viral infections, including human immunodeficiency virus (HIV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), cytomegalovirus (CMV), and parvovirus B19, are the most likely cause of glomerular podocyte damage and collapsing FSGS ( Muehlig et al, 2022 ). The main pathological features of HIV-associated nephropathy are the disappearance of the podocyte foot process, podocyte dedifferentiation, proliferation, apoptosis, podocyte detachment, and massive proteinuria ( Canaud et al, 2014 ).…”