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. 2020 Aug;31(8):1688-1695.
doi: 10.1681/ASN.2020050558. Epub 2020 Jun 19.

AKI and Collapsing Glomerulopathy Associated with COVID-19 and APOL 1 High-Risk Genotype

Huijuan Wu  1   2 , Christopher P Larsen  3 , Cesar F Hernandez-Arroyo  4 , Muner M B Mohamed  4 , Tiffany Caza  3 , Moh'd Sharshir  5 , Asim Chughtai  6 , Liping Xie  7 , Juan M Gimenez  8 , Tyler A Sandow  8 , Mark A Lusco  2 , Haichun Yang  2 , Ellen Acheampong  9 , Ivy A Rosales  9 , Robert B Colvin  9 , Agnes B Fogo  2 , Juan Carlos Q Velez  10   11
Affiliations

AKI and Collapsing Glomerulopathy Associated with COVID-19 and APOL 1 High-Risk Genotype

Huijuan Wu et al. J Am Soc Nephrol. 2020 Aug.

Abstract

Background: Kidney involvement is a feature of COVID-19 and it can be severe in Black patients. Previous research linked increased susceptibility to collapsing glomerulopathy, including in patients with HIV-associated nephropathy, to apo L1 (APOL1) variants that are more common in those of African descent.

Methods: To investigate genetic, histopathologic, and molecular features in six Black patients with COVID-19 presenting with AKI and de novo nephrotic-range proteinuria, we obtained biopsied kidney tissue, which was examined by in situ hybridization for viral detection and by NanoString for COVID-19 and acute tubular injury-associated genes. We also collected peripheral blood for APOL1 genotyping.

Results: This case series included six Black patients with COVID-19 (four men, two women), mean age 55 years. At biopsy day, mean serum creatinine was 6.5 mg/dl and mean urine protein-creatinine ratio was 11.5 g. Kidney biopsy specimens showed collapsing glomerulopathy, extensive foot process effacement, and focal/diffuse acute tubular injury. Three patients had endothelial reticular aggregates. We found no evidence of viral particles or SARS-CoV-2 RNA. NanoString showed elevated chemokine gene expression and changes in expression of genes associated with acute tubular injury compared with controls. All six patients had an APOL1 high-risk genotype. Five patients needed dialysis (two of whom died); one partially recovered without dialysis.

Conclusions: Collapsing glomerulopathy in Black patients with COVID-19 was associated with high-risk APOL1 variants. We found no direct viral infection in the kidneys, suggesting a possible alternative mechanism: a "two-hit" combination of genetic predisposition and cytokine-mediated host response to SARS-CoV-2 infection. Given this entity's resemblance with HIV-associated nephropathy, we propose the term COVID-19-associated nephropathy to describe it.

Keywords: APOL1; COVID-19; SARS-CoV-2; collapsing glomerulopathy; kidney biopsy; nephrotic.

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Figures

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Graphical abstract
Figure 1.
Figure 1.
Collapsing glomerulopathy, showing collapse of glomerular tuft with overlying hypertrophy and hyperplasia of visceral epithelial cells and marked protein droplets in cases 1–6. Arrow, early segmental collapsing lesion. #1–#4 and #6, Jones methenamine silver; #5, Periodic acid–Schiff; original magnification, ×500 in #1 and ×400 in #2–#6.
Figure 2.
Figure 2.
All biopsies show acute tubular injury with frequent tubular protein droplets. Arrow in #1, tubular protein droplets. In addition, case 2 (#2) showed diffuse patchy pleomorphic interstitial infiltrate with neutrophils and tubulitis, and rare tubules with intratubular neutrophils (arrows); case 3 (#3) showed focal acute interstitial nephritis with occasional foci of eosinophils (arrows), and microcystic tubules were present in all cases except #3. #1, #4–#6, Periodic acid–Schiff; #2 and #3, hematoxylin and eosin; original magnification, ×400 in #1–#3 and ×200 in #4–#6.
Figure 3.
Figure 3.
Transmission EM shows extensive foot process effacement and moderate microvillous transformation of podocytes in all cases. EM shows occasional reticular aggregates (arrow) in cytoplasm of endothelial cells (representative picture from #1). Original magnification, ×4400 in #1, top left; ×2200 in #2–#3; ×6000 in #4; ×8000 in #5; ×14,000 in #1, bottom right.
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