COVID-19-related collapsing glomerulopathy revealing a rare risk variant of APOL1: lessons for the clinical nephrologist

Laboux, Timothée; Gibier, Jean-Baptiste; Pottier, Nicolas; Guilhot, François; Hamroun, Aghilès

doi:10.1007/s40620-020-00935-6

Cited by 14 publications

(16 citation statements)

References 21 publications

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“… 228 – 232 Collapsing glomerulopathy is a distinct pathology related to COVID-19, which may affect patients carrying high-risk APOL1 genotypes. 233 , 234 Kidney biopsy of COVID-19 patients who had APOL1 high-risk genotype showed collapsing glomerulopathy, tubuloreticular inclusions in endothelial cells, and acute tubular injury, without evidence of SARS-CoV-2 infection or replication in kidney cells. 227 During viral infection, IFN and TLR3 activation is sufficient to upregulate APOL1 gene expression.…”

Section: Extrapulmonary Complicationsmentioning

confidence: 98%

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The mechanism underlying extrapulmonary complications of the coronavirus disease 2019 and its therapeutic implication

Ning

Wang

et al. 2022

Sig Transduct Target Ther

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The coronavirus disease 2019 (COVID-19) is a highly transmissible disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that poses a major threat to global public health. Although COVID-19 primarily affects the respiratory system, causing severe pneumonia and acute respiratory distress syndrome in severe cases, it can also result in multiple extrapulmonary complications. The pathogenesis of extrapulmonary damage in patients with COVID-19 is probably multifactorial, involving both the direct effects of SARS-CoV-2 and the indirect mechanisms associated with the host inflammatory response. Recognition of features and pathogenesis of extrapulmonary complications has clinical implications for identifying disease progression and designing therapeutic strategies. This review provides an overview of the extrapulmonary complications of COVID-19 from immunological and pathophysiologic perspectives and focuses on the pathogenesis and potential therapeutic targets for the management of COVID-19.

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Section: Extrapulmonary Complicationsmentioning

confidence: 98%

“… 235 These findings suggest plausible mechanisms involving “two-hit” of cytokine-mediated host response to SARS-CoV-2 infection and genetic susceptibility. 227 , 233 …”

Section: Extrapulmonary Complicationsmentioning

confidence: 99%

The mechanism underlying extrapulmonary complications of the coronavirus disease 2019 and its therapeutic implication

Ning

Wang

et al. 2022

Sig Transduct Target Ther

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“…Beside reports of minimal change disease, membranous nephropathy, anti-glomerular basement membrane glomerulonephritis, IgA-vasculitis, lupus nephritis and crescentic glomerulonephritis ( 56 – 58 ) associated with SARS-CoV-2, cases of cFSGS displaying similar lesions, observed in HIVAN, have led to the emergence of the SARS-CoV-2 associated entity named “COVAN” ( 59 ). COVAN patients mostly present with severe AKI and nephrotic range proteinuria in native kidneys and kidney allografts ( 60 – 62 ).…”

Section: Covid-associated Nephropathy (Covan)mentioning

confidence: 99%

Collapsing Focal Segmental Glomerulosclerosis in Viral Infections

et al. 2022

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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.

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“…Direct viral podocyte invasion is supported by electron microscopy findings of coronavirus particles within the cytoplasm of podocytes in native and post-mortem biopsies. Suggestions of CG secondary to cytokine release from systemic COVID-19 manifestations have been proposed, particularly in those with APOL1 high risk genotype and African-Caribbean ethnicity[ 13 - 22 , 24 - 29 ]. Basic-science studies have shown viral infections stimulating interferon production which in turn encourages APOL1 gene expression[ 74 ].…”

Section: Discussionmentioning

confidence: 99%

Native and transplant kidney histopathological manifestations in association with COVID-19 infection: A systematic review

Jeyalan¹,

Storrar²,

Wu³

et al. 2021

WJT

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BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can result in clinically significant multi-system disease including involvement in the kidney. The underlying histopathological processes were unknown at the start of the pandemic. As case reports and series have been published describing the underlying renal histopathology from kidney biopsies, we have started to gain an insight into the renal manifestations of this novel disease. AIM To provide an overview of the current literature on the renal histopathological features and mechanistic insights described in association with coronavirus disease 2019 (COVID-19) infection. METHODS A systematic review was performed by conducting a literature search in the following websites-‘PubMed’, ‘Web of Science’, ‘Embase’ and ‘Medline-ProQuest’ with the following search terms-“COVID-19 AND kidney biopsy”, “COVID-19 AND renal biopsy”, “SARS-CoV-2 AND kidney biopsy” and “SARS-CoV-2 AND renal biopsy”. We have included published data up until February 15, 2021, which includes kidney biopsies (native, transplant and postmortem) from patients with COVID-19. Data on clinical presentation, histopathological features, management and outcome was extracted from the reported studies. RESULTS The total number of biopsies reported on here is 288, of which 189 are postmortem, 84 native and 15 transplants. The results are varied and show underlying pathologies ranging from collapsing glomerulopathy and acute tubular injury (ATI) to anti-nuclear cytoplasmic antibody associated vasculitis and pigment nephropathy. There was variation in the specific treatment used for the various renal conditions, which included steroids, hydroxychloroquine, eculizumab, convalescent plasma, rituximab, anakinra, cyclophosphamide and renal replacement therapy, amongst others. The pathological process which occurs in the kidney following COVID-19 infection and leads to the described biopsy findings has been hypothesized in some conditions but not others (for example, sepsis related hypoperfusion for ATI). It is important to note that this represents a very small minority of the total number of cases of COVID-19 related kidney disease, and as such there may be inherent selection bias in the results described. Further work will be required to determine the pathogenetic link, if any, between COVID-19 and the other renal pathologies. CONCLUSION This report has clinical relevance as certain renal pathologies have specific management, with the implication that kidney biopsy in the setting of renal disease and COVID-19 should be an early consideration, dependent upon the clinical presentation.

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COVID-19-related collapsing glomerulopathy revealing a rare risk variant of APOL1: lessons for the clinical nephrologist

Cited by 14 publications

References 21 publications

The mechanism underlying extrapulmonary complications of the coronavirus disease 2019 and its therapeutic implication

The mechanism underlying extrapulmonary complications of the coronavirus disease 2019 and its therapeutic implication

Collapsing Focal Segmental Glomerulosclerosis in Viral Infections

Native and transplant kidney histopathological manifestations in association with COVID-19 infection: A systematic review

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