COVID-19–Related Collapsing Glomerulopathy in a Kidney Transplant Recipient

Abstract

We report a case of a kidney transplant recipient who presented with acute kidney injury and nephrotic-range proteinuria in a context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Kidney biopsy revealed collapsing glomerulopathy. Droplet-based digital polymerase chain reaction did not detect the presence of SARS-CoV-2 RNA in the biopsy fragment, and the virus was barely detectable in plasma at the time of the biopsy. SARS-CoV-2 RNAemia peaked several days later, followed by a seroconversion despite the absence of circulating CD19-positive lymphocytes at admission due to rituximab-based treatment of antibody-mediated rejection 3 months earlier. Genotyping for the 2 risk alleles of the apolipoprotein L1 (APOL1) gene revealed that the donor carried the low-risk G0/G2 genotype. This case illustrates that coronavirus disease 2019 infection may promote a collapsing glomerulopathy in kidney allografts with a low-risk APOL1 genotype in the absence of detectable SARS-CoV-2 RNA in the kidney and that podocyte injury may precede SARS-CoV-2 RNAemia. Complete author and article information provided before references.

COVID-19-associated glomerulopathy and high-risk APOL1 genotype; Basis for a two-hit mechanism of injury? A narrative review on recent findings

“…His renal biopsy findings support the diagnosis of CG concomitant with oxalate nephropathy because of high dosage of vitamin C. The APOL-1 risk variants expressed heterozygous of wild type and G1 variants, which are regarded as low-risks for CG. These case reports suggested that CG might be promoted by COVID-19 even in the presence of a low-risk APOL1 genotype (3,19). Previous studies have shown that the APOL1 risk alleles are related to an increased proportion of newly diagnosed CG.…”

“…Studies have also shown that baseline chronic kidney disease (CKD) or pre-existing acute renal impairment is associated with increased mortality (4,9). Renal tropism of this virus was detected by viral RNA in various renal structures of individuals who died from SARS-CoV-2, inclusive of glomeruli (3). In a more recent meta-analysis of five relevant studies and 964 COVID-19 positive patients, the cumula tive event rate of acute renal failure was 7.1% (95% confidence interval [CI]: 1.8%-24.5%, P<0.001, I 2 = 92.4) (10).…”

“…The virus may involve many other organs in severe cases, either directly or indirectly via a systemic hyperinflammatory response. A number of studies also reported acute renal dysfunction and other urinary abnormalities in the setting of moderate to severe COVID-19 disease (3). The precise mechanism of renal involvement and injury by SARS-CoV- 2 has not yet been fully elucidated; but more and more data is accumulating on this topic.…”

SARS-CoV-2-Associated Nephropathy: Direct Renal Infection and Damage

“…To date, case reports of patients with African background with AKI, nephrotic proteinuria, and a histopathological picture of collapsing glomerulopathy have been published. 33,[40][41][42][43][44][45][46] The majority of the patients had an apolipoprotein L1 (APOL1) high-risk genotype, [40][41][42][43] which also cannot be excluded for the patients who did not perform a genetic investigation. 33,[43][44][45] Patients with the G1 and G2 alleles of the APOL1 gene, in their vast majority of Sub-Saharan African descent, are known to be susceptible to chronic kidney disease and glomerulopathies such as focal segmental glomerulosclerosis and HIVassociated nephropathy.…”

“…Lazareth et al 46 have reported a case of collapsing glomerulopathy in a kidney transplant recipient of Sub-Saharan African origin, as well as SARS-CoV-2 infection with a low-risk donor of APOL1 genotype G0/G2, where the genotype of the recipient was G0/G0. This case report illustrates that a high-risk APOL1 donor background is not a prerequisite for severe podocyte injury to occur in kidney allografts in the context of SARS-CoV-2.…”