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

Abstract

BackgroundKidney 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.MethodsTo 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.ResultsThis 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.ConclusionsCollapsing 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.

COVID-19 Extrapulmonary illness - The Impact of COVID-19 on Nephrology care

“…From the same group, 3 patients, all African American (AA), out of 161 patients with CoV-AKI with findings suggestive of glomerular disease underwent kidney biopsy which revealed collapsing glomerulopathy in each biopsy 6 . This is in line with emerging reports of collapsing glomerulopathy in AA individuals who are carriers of the Apolipoprotien L1 (APOL1) high risk genotype and acquire COVID-19 14 , 15 . Thus, collapsing glomerulopathy should be suspected in AA individuals presenting with AKI and new onset nephrotic range proteinuria, where the COVID-19 potentially serves as a second hit.…”

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

“…49,50 Therefore, these delays meant that most patients in our cohort may have cleared virus from their kidney and were therefore RT-PCR negative by nasopharyngeal J o u r n a l P r e -p r o o f swab at the time of biopsy. Even with this caveat, most recent biopsy and autopsy case series have concluded that there is no significant SARS-CoV-2 infection of the kidney, 16,20,24,48,[51][52][53] which is in contrast to the possibility of direct infection that was reported in two earlier studies. 11,45 Therefore, our study adds to the accumulating evidence that direct and persistent infection of the kidney by SARS-CoV-2 does not appear to play a significant role in kidney disease in most COVID-19 patients.…”

Severe Acute Respiratory Syndrome Coronavirus 2 Induced Focal Segmental Glomerulosclerosis

“…Many viral infections can cause FSGS including human immunodeficiency virus 1 (HIV-1), cytomegalovirus, parvovirus B19 and Epstein-Barr virus [8,9]. Histologically, the collapsing variant shows segmental or global mesangial consolidation and loss of endocapillary patency in association with extra-capillary epithelial hypertrophy and/or proliferation [8].…”