Genetics Meets Infection: A Case of Parvovirus B19-Induced Collapsing FSGS in the Context of APOL1 High-Risk Genotype

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Introduction: Collapsing focal segmental glomerulosclerosis (cFSGS) is a severe variant of FSGS, often associated with viral infections and linked to high-risk APOL1 genotypes predominantly found in individuals of recent African ancestry. Case Description: A 41-year-old Black female with a history of hypertension and diabetes was referred for evaluation of acute kidney injury and new-onset proteinuria. She reported a self-limited episode of diarrhea and rash several months prior. At presentation, creatinine was 2.4 mg/dL, and urine protein/creatinine ratio was 5920 mg/g. Serologic workup was unremarkable. Kidney biopsy revealed cFSGS and chronic active tubulointerstitial nephritis (figure 1). Parvovirus B19 IgG was positive with low-level PCR, indicating past infection. Genetic testing revealed a high-risk APOL1 genotype (G1/G2). The patient was started on RAAS blockade and corticosteroids, resulting in improved proteinuria (1100 mg/g) and stabilized renal function (creatinine 1.6 mg/dL). Discussion: This case represents a subacute form of cFSGS, triggered by prior parvovirus B19 infection in the setting of high-risk APOL1 genotype (G1/G2). The presence two APOL1 risk alleles is associated with increased susceptibility to cFSGS, particularly in individuals of recent African descent when combined with a "second hit" such as viral infections.Parvovirus B19 can directly infect renal epithelial cells, including podocytes, leading to cellular injury and collapse. In genetically predisposed individuals, this viral insult may initiate or accelerate cFSGS. Management typically includes treatment of the underlying infection and immunosuppressive therapy—such as corticosteroids and calcineurin inhibitors. Despite intervention, the prognosis remains poor, with many patients progressing to ESKD.

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