APOL1-Associated Collapsing Focal Segmental Glomerulosclerosis in a Patient With Stimulator of Interferon Genes (STING)-Associated Vasculopathy With Onset in Infancy (SAVI)

Abstract

Apolipoprotein L1 (APOL1) risk variants G1 and G2 are known to result in risk for kidney disease in patients of African ancestry. APOL1-associated nephropathy typically occurs in association with certain environmental factors or systemic diseases. As such, there has been increasing evidence of the role of interferon (IFN) pathways in the pathogenesis of APOL1-associated collapsing glomerulopathy in patients with human immunodeficiency virus (HIV) infection and systemic lupus erythematosus, 2 conditions that are associated with high IFN levels. Collapsing glomerulopathy has also been described in patients receiving exogenous IFN therapy administered for various medical conditions. We describe a patient with a genetic condition that results in an increased IFN state, stimulator of IFN genes (STING)-associated vasculopathy with onset in infancy (SAVI), who developed collapsing glomerulopathy during a flare of his disease. The patient was found to have APOL1 G1 and G2 risk variants. This case supports the role of IFN in inducing APOL1-associated collapsing glomerulopathy.

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

“…[16][17][18][19][20] The mechanism driving this acute glomerular injury process is possibly related to interferon production, a known trigger of collapsing glomerulopathy. [21][22][23] It is less likely that direct podocyte infection is an etiologic factor as the 3/4 patients who were negative for virus by IHC and/or in situ hybridization had podocytopathies (1 each FSGS, collapsing glomerulopathy and minimal change disease). We were able to genotype one Black patient (case 1) who was found to carry the high risk G1/G1 APOL1 genotype.…”

Adult-Onset ANCA-Associated Vasculitis in SAVI: Extension of the Phenotypic Spectrum, Case Report and Review of the Literature

“…Across the 56 surveyed patients, vasculopathy resulting from vasculitis and endothelial cell death is a hallmark of SAVI mostly affecting the skin, lungs and central nervous system ( 1 , 4 ). Clinically this commonly manifested as chilblains (33.9%), telangiectasia (32.1%), livedo reticularis (32.1%) and Raynaud phenomena (12.5%).…”

“…Clinically this commonly manifested as chilblains (33.9%), telangiectasia (32.1%), livedo reticularis (32.1%) and Raynaud phenomena (12.5%). Sometimes, more severe manifestations occurred such as acral ischemia necessitating amputations (21.4%) or ischemic/hemorrhagic stroke (5.4%) ( 1 , 4 ). Cutaneous manifestations were common in SAVI, mostly with erythematous, malar, maculopapular rashes, and acral violaceous plaques (46.4%) with or without concomitant nail dystrophy (21.4%).…”

“…One patient of African-American ethnicity, presenting with skin vasculopathy and ILD, developed generalized edema due to nephrotic range proteinuria at the age of 14 months ( 4 ). Renal biopsy showed focal segmental glomerulosclerosis ( 4 ). Of note, this patient also carried two APOL1 risk variants which are associated with this kidney disease.…”

The effect of APOL1 risk variants on emergent outcomes in kidney disorders: A meta-analysis of individual participant data

“…Finally12 published articles were included in this study. These 12 articles included 20 case reports that were examined 20 patients at risk APOL1 genotype and renal dysfunction for qualitative and quantitative synthesis [13][14][15][16][17][18][19][20][21][22][23][24]. Eleven of twenty patients (11/20, 55%) were from Afro-American ethnicity, four of twenty patients (4/20, 20%) from the Caribbean, three of twenty patients from white ancestry (3/20, 15%) and one patient (1/20, 5%) from Asian and black race.…”