FSGS and COVID-19 in Non-African American Patients.

Collapsing Focal Segmental Glomerulosclerosis (FSGS) has been reported relatively frequently in African American (AA) patients with coronavirus disease 2019 (COVID-19), and it is associated almost always with Apolipoprotein L gen 1 (APOL1) high-risk variants. We reviewed the published literature from April 2020 to November 2022 searching for non-African American (non-AA) patients with FSGS associated with COVID-19 (eight White patients, six Hispanic patients, three Asian patients, one Indian patient, and one Asian Indian patient). The following histologic patterns were found: collapsing (n=11), not otherwise specified (n=5), tip (n=2), and perihilar (n=1). Fifteen of the 19 patients had AKI. The APOL1 genotype was reported in only six of the 19 non-AA patients. Three of them (two Hispanic patients and one White patient) with collapsing FSGS had high-risk APOL1 variants. The other three patients (two White patients and one Hispanic patient with the collapsing variant, tip variant, and not otherwise specified) had low-risk APOL1 variants. Among 53 African American patients with collapsing FSGS associated with COVID-19, 48 had high-risk APOL1 variants and five had low-risk APOL1 variants. We conclude that in non-AA patients, FSGS is a rare complication of COVID-19. FSGS associated with COVID-19 can occur rarely with low-risk APOL1 variants in non-AA and AA patients. Non-AA patients reported to be associated with high-risk APOL1 variants possibly reflect inaccuracy of self-reported race with AA admixture because of unknown ancestry. Given the importance of APOL1 in the pathogenesis of FSGS associated with viral infection and to avoid racial bias, it seems appropriate that APOL1 testing be considered in patients with FSGS associated with COVID-19, regardless of self-reported race.

Early recurrence of focal segmental glomerulosclerosis in a kidney transplant recipient with APOL1 one risk variant.

Apolipoprotein 1 (APOL1) risk variants (G1 and G2) are associated with focal segmental glomerulosclerosis (FSGS) in patients of African ancestry. The prevalence of APOL1 two risk variants is lower in Hispanics and very rare in European and Asian populations. APOL1 two risk variants in donor kidneys is associated with recipient kidney graft loss, however the effect of recipient risk variant in the kidney transplant outcome is unclear. Here, we present a late adolescent male with FSGS and end stage renal disease with one APOL1 risk variant (G2) who had immediate recurrence of FSGS in the post-KT period. There was an excellent response to few sessions of plasmapheresis and Rituximab with no further recurrence of FSGS in the 1 year follow-up period. It needs to be seen whether the recipient APOL1 single risk variant causes increased susceptibility to kidney graft loss on a long run via recurrent or de novo pathologies.

Sex and kidney ACE2 expression in primary focal segmental glomerulosclerosis: A NEPTUNE study.

BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) has been implicated in the pathogenesis of experimental kidney disease. ACE2 is on the X chromosome, and in mice, deletion of ACE2 leads to the development of focal segmental glomerulosclerosis (FSGS). The relationship between sex and renal ACE2 expression in humans with kidney disease is a gap in current knowledge. METHODS: We studied renal tubulointerstitial microarray data and clinical variables from subjects with FSGS enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) study. We compared relationships between ACE2 expression and age, estimated glomerular filtration rate (eGFR), urinary albumin to creatinine ratio (UACR), interstitial fibrosis, tubular atrophy, and genes implicated in inflammation and fibrosis in male and female subjects. RESULTS: ACE2 mRNA expression was lower in the tubulointerstitium of males compared to females (P = 0.0026). Multiple linear regression analysis showed that ACE2 expression was related to sex and eGFR but not to age or treatment with renin angiotensin system blockade. ACE2 expression is also related to interstitial fibrosis, and tubular atrophy, in males but not in females. Genes involved in inflammation (CCL2 and TNF) correlated with ACE2 expression in males (TNF: r = -0.65, P < 0.0001; CCL2: r = -0.60, P < 0.0001) but not in females. TGFB1, a gene implicated in fibrosis correlated with ACE2 in both sexes. CONCLUSIONS: Sex is an important determinant of ACE2 expression in the tubulointerstitium of the kidney in FSGS. Sex also influences the relationships between ACE2, kidney fibrosis, and expression of genes involved in kidney inflammation.