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

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) gen...

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Published in:Nephrology, dialysis, transplantation dialysis, transplantation, 2017-06, Vol.32 (6), p.983-990
Main Authors: Ng, Derek K, Robertson, Catherine C, Woroniecki, Robert P, Limou, Sophie, Gillies, Christopher E, Reidy, Kimberly J, Winkler, Cheryl A, Hingorani, Sangeeta, Gibson, Keisha L, Hjorten, Rebecca, Sethna, Christine B, Kopp, Jeffrey B, Moxey-Mims, Marva, Furth, Susan L, Warady, Bradley A, Kretzler, Matthias, Sedor, John R, Kaskel, Frederick J, Sampson, Matthew G
Format: Article
Language:English
Subjects:
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
Original
Polymorphism, Single Nucleotide
Prospective Studies
United States
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Summary: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. 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). 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). 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.
ISSN:0931-0509
1460-2385
DOI:10.1093/ndt/gfw061