• 1.

    Su H, et al.. Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China. Kidney Int 2020; 98:219227. doi: 10.1016/j.kint.2020.04.003

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Farkash EA, et al.. Ultrastructural evidence for direct renal infection with SARS-CoV-2. J Am Soc Nephrol 2020; 31:16831687. doi: 10.1681/ASN.2020040432

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Calomeni E, et al.. Multivesicular bodies mimicking SARS-CoV-2 in patients without COVID-19. Kidney Int 2020; 98:233234. doi: 10.1016/j.kint.2020.05.003

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Smith KD, et al.. Am I a coronavirus? Kidney Int 2020; 98:506507. doi: 10.1016/j.kint.2020.05.021

  • 5.

    Puelles VG, et al.. Multiorgan and renal tropism of SARS-CoV-2. N Engl J Med 2020; 383:590592. doi: 10.1056/NEJMc2011400

  • 6.

    Sharma P, et al.. COVID-19-associated kidney injury: A case series of kidney biopsy findings. J Am Soc Nephrol 2020; 31:19481958. doi: 10.1681/ASN.2020050699

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Golmai P, et al.. Histopathologic and ultrastructural findings in postmortem kidney biopsy material in 12 patients with AKI and COVID-19. J Am Soc Nephrol 2020; 31:19441947. doi: 10.1681/ASN.2020050683

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Santoriello D, et al.. Postmortem kidney pathology findings in patients with COVID-19. J Am Soc Nephrol 2020; 31:21582167. doi: 10.1681/ASN.2020050744

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Kudose S, et al.. Kidney biopsy findings in patients with COVID-19. J Am Soc Nephrol 2020; 31:19591968. doi: 10.1681/ASN.2020060802

  • 10.

    Wu H, et al.. AKI and collapsing glomerulopathy associated with COVID-19 and APOL1 high-risk genotype. J Am Soc Nephrol 2020; 31:16881695. doi: 10.1681/ASN.2020050558

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11.

    Sharma P, et al.. Pathology of COVID 19 associated acute kidney injury. Clin Kidney J [published online ahead of print January 24, 2021]. https://academic.oup.com/ckj/advance-article/doi/10.1093/ckj/sfab003/6118199

    • Search Google Scholar
    • Export Citation
  • 12.

    Nasr SH, et al.. Kidney biopsy findings in patients with COVID-19, kidney injury, and proteinuria. Am J Kidney Dis 2021; 77:465468. doi: 10.1053/j.ajkd.2020.11.002

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13.

    Nichols B, et al.. Innate immunity pathways regulate the nephropathy gene apolipoprotein L1. Kidney Int 2015; 87:332342. doi: 10.1038/ki.2014.270

  • 14.

    Velez JCQ, et al.. COVAN is the new HIVAN: The re-emergence of collapsing glomerulopathy with COVID-19. Nat Rev Nephrol 2020; 16:565567. doi: 10.1038/s41581-020-0332-3

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15.

    Yamada M, et al.. Minimal change disease with nephrotic syndrome associated with coronavirus disease 2019 after apolipoprotein L1 risk variant kidney transplant: A case report. Transplant Proc 2020; 52:26932697. doi: 10.1016/j.transproceed.2020.08.012

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16.

    Fousert E, et al.. Neutrophil extracellular traps (NETs) take the central stage in driving autoimmune responses. Cells 2020; 9:915. doi: 10.3390/cells9040915

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17.

    Akilesh S, et al.. Multicenter clinicopathologic correlation of kidney biopsies performed in COVID-19 patients presenting with acute kidney injury or proteinuria. Am J Kidney Dis 2021; 77:8293.e1. doi: 10.1053/j.ajkd.2020.10.001

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18.

    Jhaveri KD, et al.. Thrombotic microangiopathy in a patient with COVID-19. Kidney Int 2020; 98:509512. doi: 10.1016/j.kint.2020.05.025

  • 19.

    Perico L, et al.. Immunity, endothelial injury and complement-induced coagulopathy in COVID-19. Nat Rev Nephrol 2021; 17:4664. doi: 10.1038/s41581-020-00357-4

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20.

    Fontana F, et al.. Oxalate nephropathy caused by excessive vitamin C administration in 2 patients with COVID-19. Kidney Int Rep 2020; 5:18151822. doi: 10.1016/j.ekir.2020.07.008

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21.

    Bomback AS, et al.. How COVID-19 has changed the management of glomerular diseases. Clin J Am Soc Nephrol 2020; 15:876879. doi: 10.2215/CJN.04530420

Glomerular Diseases Associated with COVID-19

  • 1 Purva Sharma is with the Division of Kidney Diseases and Hypertension and the Glomerular Center at Northwell Health, Hempstead, NY. Vanesa Bijol is with the Glomerular Center at Northwell Health and the Department of Pathology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health, Hempstead, NY.
Full access

As the coronavirus infectious disease 2019 (COVID-19) pandemic unleashed through the world, we found that patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) had a wide range of direct and indirect effects culminating in a variety of end-organ injuries. Acute kidney injury (AKI) was found in as many as 80% of patients admitted to the intensive care unit with severe illness.

The most common histopathologic equivalent of clinical AKI was acute tubular injury or necrosis in biopsy and autopsy studies in these patients. However, COVID-19 can affect all compartments of the kidney parenchyma, including the glomerulus, interstitium, and vasculature. The tubulointerstitial injury is non-inflammatory and without viral cytopathic effect; however, a number of reports claimed direct viral infection of tubules or podocytes on electron microscopy, which was quickly disputed by others (1−4). Some authors have reported the positive findings by immunohistochemistry, immunofluorescence, or in situ hybridization (1, 5), whereas others have interpreted their results as negative using the same techniques (69). All of this, together with the fact that viremia or viruria are rarely detected clinically, suggests that indirect mechanisms related to cytokine release are of utmost importance for the mechanisms of AKI, as well as the injury to other tissues, organs, and systems including the coagulation and complement pathways. Hemodynamic factors and medication-induced kidney injury also remain important causative factors for AKI in COVID-19.

A variety of glomerular diseases have been reported in patients with COVID-19, some triggered or exacerbated by COVID-19 or likely independent of it (Figure 1). Collapsing glomerulopathy (CG) has a special predilection for patients with African ancestry who are homozygous for high-risk APOL1 genotypes (10). In a recent review (11), 32 cases of CG were reported, out of which 21 had APOL1 polymorphisms. Ninety-six percent of these patients were of African or African-American heritage. Nasr et al. (12) reported eight cases of CG, all of whom were Black. The mechanism is thought to be activation of the host interferon-chemokine pathway leading to upregulation of the APOL1 variant gene and disruption of podocyte autophagy, rather than direct infection of the glomerular cells (13). This association of CG with COVID-19 has bought itself a new name, COVAN, or COVID-19-associated nephropathy (14).

Figure 1.
Figure 1.

Glomerular diseases in COVID-19

Citation: Kidney News 13, 4

Figure created by Purva Sharma and Kenar Jhaveri using BioRender (biorender.com)

The treatment of COVID-19-associated CG is controversial. Treatment of the underlying disease as is done in other infections associated with CG is likely of benefit, although data on treatment outcomes in these patients are lacking. Steroids have been used in CG with persistent nephrotic-range proteinuria, but without evidence-based guidelines and consideration of the potential for harm in COVID-19 sepsis, their widespread use cannot be endorsed. Given that an inflammatory cascade and cytokine storm play a major role, there may be some benefit with the interleukin 6 (IL-6) receptor blockade, although this remains entirely speculative. A correlation with other podocytopathies, including minimal change disease and focal segmental glomerulosclerosis (FSGS), is less clear but likely involves T cell activation and cytokine release (15).

There have been case reports of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in patients with SARS-CoV-2 infection. The role of neutrophil extracellular traps (NETs) in the pathogenesis of AAV has been studied in the past, so new insights into the role of NETs in pathogenesis of COVID-19 naturally raise the question of association of AAV and COVID-19, although this remains to be proven (16). Anti-glomerular basement membrane (GBM) disease, immunoglobulin A (IgA) vasculitis, and membranous nephropathy (either phospholipase A2 receptor [PLA2R] positive or negative) have been reported as well. A reported case of crescentic transformation of pre-existing lupus nephritis emphasizes the potential importance of an inflammatory milieu in patients with COVID-19, leading to worsening of their preexisting disease (9).

Thrombotic microangiopathies, through complement-induced coagulopathy and other indirect mechanisms of endothelial cell injury, have been reported, often with severe clinical course, requiring dialysis, and with high mortality (17−19).

Of tubulointerstitial diseases, apart from acute tubular injury, with or without necrosis, there have been reports of myoglobin cast nephropathy due to rhabdomyolysis (6, 9) and occasional reports of medication-induced kidney injury (drug-induced acute interstitial nephritis [AIN] and kidney oxalosis in mega doses of vitamin C) (20).

Overall, as the field of glomerular diseases grows, we need to carry forward the lessons learned from COVID-19, most importantly, how patients should be managed, weighing the risks and benefits of immunosuppression and reducing environmental exposure including incorporation of telemedicine (21). These will be important considerations in the future in this high-risk population to reduce glomerular disease burden and relapse.

The authors report no conflicts of interest to disclose.

References

  • 1.

    Su H, et al.. Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China. Kidney Int 2020; 98:219227. doi: 10.1016/j.kint.2020.04.003

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Farkash EA, et al.. Ultrastructural evidence for direct renal infection with SARS-CoV-2. J Am Soc Nephrol 2020; 31:16831687. doi: 10.1681/ASN.2020040432

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Calomeni E, et al.. Multivesicular bodies mimicking SARS-CoV-2 in patients without COVID-19. Kidney Int 2020; 98:233234. doi: 10.1016/j.kint.2020.05.003

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Smith KD, et al.. Am I a coronavirus? Kidney Int 2020; 98:506507. doi: 10.1016/j.kint.2020.05.021

  • 5.

    Puelles VG, et al.. Multiorgan and renal tropism of SARS-CoV-2. N Engl J Med 2020; 383:590592. doi: 10.1056/NEJMc2011400

  • 6.

    Sharma P, et al.. COVID-19-associated kidney injury: A case series of kidney biopsy findings. J Am Soc Nephrol 2020; 31:19481958. doi: 10.1681/ASN.2020050699

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Golmai P, et al.. Histopathologic and ultrastructural findings in postmortem kidney biopsy material in 12 patients with AKI and COVID-19. J Am Soc Nephrol 2020; 31:19441947. doi: 10.1681/ASN.2020050683

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Santoriello D, et al.. Postmortem kidney pathology findings in patients with COVID-19. J Am Soc Nephrol 2020; 31:21582167. doi: 10.1681/ASN.2020050744

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Kudose S, et al.. Kidney biopsy findings in patients with COVID-19. J Am Soc Nephrol 2020; 31:19591968. doi: 10.1681/ASN.2020060802

  • 10.

    Wu H, et al.. AKI and collapsing glomerulopathy associated with COVID-19 and APOL1 high-risk genotype. J Am Soc Nephrol 2020; 31:16881695. doi: 10.1681/ASN.2020050558

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11.

    Sharma P, et al.. Pathology of COVID 19 associated acute kidney injury. Clin Kidney J [published online ahead of print January 24, 2021]. https://academic.oup.com/ckj/advance-article/doi/10.1093/ckj/sfab003/6118199

    • Search Google Scholar
    • Export Citation
  • 12.

    Nasr SH, et al.. Kidney biopsy findings in patients with COVID-19, kidney injury, and proteinuria. Am J Kidney Dis 2021; 77:465468. doi: 10.1053/j.ajkd.2020.11.002

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13.

    Nichols B, et al.. Innate immunity pathways regulate the nephropathy gene apolipoprotein L1. Kidney Int 2015; 87:332342. doi: 10.1038/ki.2014.270

  • 14.

    Velez JCQ, et al.. COVAN is the new HIVAN: The re-emergence of collapsing glomerulopathy with COVID-19. Nat Rev Nephrol 2020; 16:565567. doi: 10.1038/s41581-020-0332-3

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15.

    Yamada M, et al.. Minimal change disease with nephrotic syndrome associated with coronavirus disease 2019 after apolipoprotein L1 risk variant kidney transplant: A case report. Transplant Proc 2020; 52:26932697. doi: 10.1016/j.transproceed.2020.08.012

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16.

    Fousert E, et al.. Neutrophil extracellular traps (NETs) take the central stage in driving autoimmune responses. Cells 2020; 9:915. doi: 10.3390/cells9040915

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17.

    Akilesh S, et al.. Multicenter clinicopathologic correlation of kidney biopsies performed in COVID-19 patients presenting with acute kidney injury or proteinuria. Am J Kidney Dis 2021; 77:8293.e1. doi: 10.1053/j.ajkd.2020.10.001

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18.

    Jhaveri KD, et al.. Thrombotic microangiopathy in a patient with COVID-19. Kidney Int 2020; 98:509512. doi: 10.1016/j.kint.2020.05.025

  • 19.

    Perico L, et al.. Immunity, endothelial injury and complement-induced coagulopathy in COVID-19. Nat Rev Nephrol 2021; 17:4664. doi: 10.1038/s41581-020-00357-4

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20.

    Fontana F, et al.. Oxalate nephropathy caused by excessive vitamin C administration in 2 patients with COVID-19. Kidney Int Rep 2020; 5:18151822. doi: 10.1016/j.ekir.2020.07.008

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21.

    Bomback AS, et al.. How COVID-19 has changed the management of glomerular diseases. Clin J Am Soc Nephrol 2020; 15:876879. doi: 10.2215/CJN.04530420

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