COVID-19–Associated Collapsing Focal Segmental Glomerulosclerosis: A Report of 2 Cases

Abstract

Collapsing glomerulopathy is an aggressive form of focal segmental glomerulosclerosis with diverse causes. The presence of the apolipoprotein L1 ( APOL1 ) high-risk genotype is a major risk factor for collapsing glomerulopathy in African Americans. Coronavirus disease 2019 (COVID-19) is an emerging pandemic with predominant respiratory manifestations. However, kidney involvement is being frequently noted and is associated with higher mortality. Currently, kidney pathology data for COVID-19 are scant and mostly come from postmortem findings. We report 2 African American patients who developed acute kidney injury and proteinuria in temporal association with COVID-19 infection. Kidney biopsy specimens showed collapsing glomerulopathy, endothelial tubuloreticular inclusions, and acute tubular injury, without evidence by electron microscopy or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in situ hybridization of viral infection of kidney cells. Both patients had the APOL1 high-risk genotype. We propose that collapsing glomerulopathy represents a novel manifestation of COVID-19 infection, especially in people of African descent with APOL1 risk alleles.

Multicenter Clinicopathologic Correlation of Kidney Biopsies Performed in COVID-19 Patients Presenting With Acute Kidney Injury or Proteinuria

“…We were able to genotype one Black patient (case 1) who was found to carry the high risk G1/G1 APOL1 genotype. While we did not genotype the other patients in our cohort, 6/7 patients with collapsing glomerulopathy were Black, consistent with other reports demonstrating a strong association between collapsing glomerulopathy in the setting of SARS-CoV-2 infection with high-risk APOL1 genotypes, 17,19,24 a susceptibility that parallels its incidence in HIV-infected patients. 24,25 The last patient with collapsing glomerulopathy (case 6) was a Hispanic patient from Mexico who was also found to have a high risk G2/G2 APOL1 genotype even though the prevalence of homozygous high-risk APOL1 genotypes in mainland Hispanics is 0.1%.…”

“…The most striking finding is the high incidence of collapsing glomerulopathy (7/17, 41%), which has been reported by multiple groups in association with SARS-CoV-2 infection. [16][17][18][19][20] The mechanism driving this acute glomerular injury process is possibly related to interferon production, a known trigger of collapsing glomerulopathy. [21][22][23] It is less likely that direct podocyte infection is an etiologic factor as the 3/4 patients who were negative for virus by IHC and/or in situ hybridization had podocytopathies (1 each FSGS, collapsing glomerulopathy and minimal change disease).…”

COVID‐19‐associated collapsing glomerulopathy: a report of two cases and literature review

“…In conclusion, the cases detailed in the present report strongly argue in favour of a direct causal link between SARS-CoV-2 infection and the occurrence of CG for which the term COVIDAN can be coined, as a mirror image of HIVAN, as already suggested by Wu et al 9 The cases we report confirm the recently published cases of CG in COVID-19 [7][8][9][10][11]15 and showed that patients homozygous for the APOL1 risk alleles are particularly at risk of developing this complication during the course of COVID-19. Although the long-term renal prognosis for acute renal failure during COVD- 19 is not yet known, the findings of CG among the kidney lesions induced by SARS-CoV-2 suggest that the long-term prognosis to maintain kidney function in individuals with high-risk APOL1 genotype may be far worse, as compared to those in the presence of an isolated, virus-induced, acute tubular necrosis.…”

“…Postmortem examinations from China confirmed that SARS-CoV-2 directly infects human kidney tubules and induces acute tubular damage, similar to that observed in our patients, by a direct cytopathic effect and/or the cytotoxic action of CD68 + interstitial macrophages, together with tubular deposition of complement C5b-9. 22 However, unlike Kissling et al 7 and Kadosh et al, 11 but like many others, 7,8,[10][11][12][13][14][15] we were unable to demonstrate the presence of the virus within the podocyte. However, we cannot exclude the possibility that the virus was present below the level of detection.…”

“…Fourteen original case reports of CG occurring during the course of documented COVID-19 were identified. [7][8][9][10][11][12][13][14][15] One patient reported by Wu et al 12 was previously reported individually. 7 Data collected in these case reports and in our two cases are shown in Table 2.…”