APOL1-associated glomerular disease among African-American children: a collaboration of the Chronic Kidney Disease in Children (CKiD) and Nephrotic Syndrome Study Network (NEPTUNE) cohorts

Nephrol Dial Transplant. 2017 Jun 1;32(6):983-990. doi: 10.1093/ndt/gfw061.

Abstract

Background: Individuals of African ancestry harboring two variant alleles within apolipoprotein L1 ( APOL1 ) are classified with a high-risk (HR) genotype. Adults with an HR genotype have increased risk of focal segmental glomerulosclerosis and chronic kidney disease compared with those with a low-risk (LR) genotype (0 or 1 variants). The role of APOL1 risk genotypes in children with glomerular disease is less well known.

Methods: This study characterized 104 African-American children with a glomerular disease by APOL1 genotype in two cohorts: the Chronic Kidney Disease in Children (CKiD) and Nephrotic Syndrome Study Network (NEPTUNE).

Results: Among these subjects, 46% had an HR genotype with a similar age at cohort enrollment. For APOL1 HR children, the median age of disease onset was older (CKiD: 4.5 versus 11.5 years for LR versus HR; NEPTUNE: 11 versus 14 years for LR versus HR, respectively) and preterm birth was more common [CKiD: 27 versus 4%; NEPTUNE: 26 versus 12%; combined odds ratio 4.6 (95% confidence interval: 1.4, 15.5)]. Within studies, HR children had lower initial estimated glomerular filtration rate (eGFR) (CKiD: 53 versus 69 mL/min/1.73 m 2 ; NEPTUNE: 74 versus 94 mL/min/1.73 m 2 ). Longitudinal eGFR decline was faster among HR children versus LR (CKiD: -18 versus -8% per year; NEPTUNE: -13 versus -3% per year).

Conclusions: Children with an HR genotype in CKiD and NEPTUNE seem to have a more aggressive form of glomerular disease, in part due to a higher prevalence of focal segmental glomerulosclerosis. These consistent findings across independent cohorts suggest a common natural history for children with APOL1 -associated glomerular disease. Further study is needed to determine the generalizability of these findings.

Keywords: APOL1; FSGS; epidemiology; nephrotic syndrome; pediatrics.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • African Americans / genetics
  • Age of Onset
  • Apolipoprotein L1 / genetics*
  • Child
  • Child, Preschool
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Nephrotic Syndrome / genetics*
  • Nephrotic Syndrome / pathology
  • Nephrotic Syndrome / physiopathology
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • United States

Substances

  • APOL1 protein, human
  • Apolipoprotein L1