Idiopathic collapsing glomerulopathy is associated with APOL1 high-risk genotypes or Mendelian variants in most affected individuals in a highly admixed population
Issued Date
2024-03-01
Resource Type
ISSN
00852538
eISSN
15231755
Scopus ID
2-s2.0-85185493091
Pubmed ID
38143038
Journal Title
Kidney International
Volume
105
Issue
3
Start Page
593
End Page
607
Rights Holder(s)
SCOPUS
Bibliographic Citation
Kidney International Vol.105 No.3 (2024) , 593-607
Suggested Citation
Neves P.D., Watanabe A., Watanabe E.H., Narcizo A.M., Nunes K., Lerario A.M., Ferreira F.M., Cavalcante L.B., Wongboonsin J., Malheiros D.M., Jorge L.B., Sampson M.G., Noronha I.L., Onuchic L.F. Idiopathic collapsing glomerulopathy is associated with APOL1 high-risk genotypes or Mendelian variants in most affected individuals in a highly admixed population. Kidney International Vol.105 No.3 (2024) , 593-607. 607. doi:10.1016/j.kint.2023.11.028 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/97395
Title
Idiopathic collapsing glomerulopathy is associated with APOL1 high-risk genotypes or Mendelian variants in most affected individuals in a highly admixed population
Corresponding Author(s)
Other Contributor(s)
Abstract
Collapsing glomerulopathy (CG) is most often associated with fast progression to kidney failure with an incidence apparently higher in Brazil than in other countries. However, the reason for this occurrence is unknown. To better understand this, we performed an integrated analysis of clinical, histological, therapeutic, causative genetic and genetic ancestry data in a highly genetically admixed cohort of 70 children and adult patients with idiopathic CG (ICG). The disease onset occurred at 23 (interquartile range: 17-31) years and approximately half of patients progressed to chronic kidney disease requiring kidney replacement therapy (CKD-KRT) 36 months after diagnosis. Causative genetic bases, assessed by targeted-gene panel or whole-exome sequencing, were identified in 58.6% of patients. Among these cases, 80.5% harbored APOL1 high-risk genotypes (HRG) and 19.5% causative Mendelian variants (MV). Self-reported non-White patients more frequently had HRG. MV was an independent risk factor for progression to CKD-KRT by 36 months and the end of follow-up, while remission was an independent protective factor. All patients with HRG manifested CG at 9-44 years of age, whereas in those with APOL1 low-risk genotype, the disease arose throughout life. HRGs were associated with higher proportion of African genetic ancestry. Novel causative MVs were identified in COL4A5, COQ2 and PLCE1 and previously described causative MVs were identified in MYH9, TRPC6, COQ2, COL4A3 and TTC21B. Three patients displayed HRG combined with a variant of uncertain significance (ITGB4, LAMA5 or PTPRO). MVs were associated with worse kidney prognosis. Thus, our data reveal that the genetic status plays a major role in ICG pathogenesis, accounting for more than half of cases in a highly admixed Brazilian population.