title: 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.
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.
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Derek K
authors.initials: DK
authors.lastname: Ng
authors.affiliation: Division of Pediatric Nephrology, University of Michigan School of Medicine, Ann Arbor, MI, USA.
authors.forename: Catherine C
authors.initials: CC
authors.lastname: Robertson
authors.affiliation: Stony Brook Children's Hospital, Stony Brook, NY, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Woroniecki
authors.affiliation: Basic Research Laboratory, NCI, Leidos Biomedical Inc., Frederick National Lab, Frederick, MD, USA.
authors.forename: Sophie
authors.initials: S
authors.lastname: Limou
authors.affiliation: Division of Pediatric Nephrology, University of Michigan School of Medicine, Ann Arbor, MI, USA.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Gillies
authors.affiliation: Montefiore Medical Center, Bronx, NY, USA.
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Reidy
authors.affiliation: Basic Research Laboratory, NCI, Leidos Biomedical Inc., Frederick National Lab, Frederick, MD, USA.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Winkler
authors.affiliation: University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Hingorani
authors.affiliation: University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Keisha L
authors.initials: KL
authors.lastname: Gibson
authors.affiliation: Montefiore Medical Center, Bronx, NY, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hjorten
authors.affiliation: Cohen's Children's Medical Center, New Hyde Park, NY, USA.
authors.forename: Christine B
authors.initials: CB
authors.lastname: Sethna
authors.affiliation: NIDDK, NIH, Bethesda, MD, USA.
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Kopp
authors.affiliation: Division of Kidney, Urology, and Hematology, NIDDK, NIH, Bethesda, MD, USA.
authors.forename: Marva
authors.initials: M
authors.lastname: Moxey-Mims
authors.affiliation: Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Furth
authors.affiliation: Children's Mercy Hospital, Kansas City, MO, USA.
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Warady
authors.affiliation: Internal Medicine-Nephrology, University of Michigan School of Medicine, Ann Arbor, MI, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kretzler
authors.affiliation: Case Western Reserve University, Cleveland, OH, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Sedor
authors.affiliation: Montefiore Medical Center, Bronx, NY, USA.
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Kaskel
authors.affiliation: Division of Pediatric Nephrology, University of Michigan School of Medicine, Ann Arbor, MI, USA.
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Sampson
mesh_terms: D000293:Adolescent; D001741:Black or African American / Q000235:genetics; D017668:Age of Onset; D000075944:Apolipoprotein L1 / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D009404:Nephrotic Syndrome / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D014481:United States
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1
keywords: APOL1; FSGS; epidemiology; nephrotic syndrome; pediatrics