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

Wu, Huijuan; Larsen, Christopher P; Hernandez-Arroyo, Cesar F; Mohamed, Muner M B; Caza, Tiffany; Sharshir, Moh'd; Chughtai, Asim; Xie, Liping; Gimenez, Juan M; Sandow, Tyler A; Lusco, Mark A; Yang, Haichun; Acheampong, Ellen; Rosales, Ivy A; Colvin, Robert B; Fogo, Agnes B; Velez, Juan Carlos Q

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.