Uptake of next-generation sequencing in children with end-stage renal disease secondary to focal segmental glomerulosclerosis and parental decision for kidney transplantation-Experience from a low resource setting: A Retrospective Cohort Study

Pediatr Transplant. 2021 Aug;25(5):e13960. doi: 10.1111/petr.13960. Epub 2020 Dec 26.

Abstract

Background: Transplantation is the optimal modality for children with ESRD. High risk of disease recurrence and graft loss with FSGS, and its financial implications, may result in families refusing transplantation. Deceased donation is often preferred for FSGS, but access is limited in many low- and middle-income group countries (LMIC; per capita gross national income between $1026 and $3995). As FSGS secondary to an underlying genetic etiology has low recurrence risk, we hypothesized that in LMIC such as India, families with children in ESRD secondary to FSGS with proven pathogenic mutation are more likely to consent for transplantation than those with unknown etiology.

Methods: Prospective cross-sectional study with retrospective chart review was undertaken (March 2011 and February 2019) to identify children with ESRD from FSGS. The objective was to ascertain NGS uptake and findings, parental decision for transplantation, and transplant outcome.

Results: 28 children with FSGS started transplant workup, and 15 (54%) families agreed for NGS testing. Pathogenic mutation (NPHS1 x 2, WT1 x 2, COL4A3 x 2, CD2AP, CRB2, COL4A5, INF 2, ACTN4, NPHP4: 1 each) was identified in 12 (80%). 92% (11/12) agreed to proceed with transplantation in contrast to 13% (2/16) who either did not undergo NGS testing or had no pathogenic mutation identified (P = .001). No disease recurrences were noted in those with a known pathogenic mutation.

Conclusion: In LMIC, NGS results are useful in transplant discussions with families for children with ESRD secondary to FSGS.

Keywords: end-stage renal disease; focal segmental glomerulosclerosis; kidney transplantation; next-generation sequencing; recurrence.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Cross-Sectional Studies
  • Decision Making
  • Developed Countries
  • Female
  • Follow-Up Studies
  • Genetic Markers
  • Genetic Testing / methods*
  • Glomerulosclerosis, Focal Segmental / genetics*
  • Glomerulosclerosis, Focal Segmental / physiopathology
  • High-Throughput Nucleotide Sequencing*
  • Humans
  • India
  • Infant
  • Infant, Newborn
  • Kidney Failure, Chronic / etiology
  • Kidney Failure, Chronic / surgery*
  • Kidney Transplantation / psychology*
  • Male
  • Mutation
  • Parental Consent / psychology*
  • Prospective Studies
  • Recurrence
  • Retrospective Studies
  • Risk
  • Sequence Analysis, DNA

Substances

  • Genetic Markers