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Background: Two genetic variants in apolipoprotein L1 (APOL1) are associated with increased risk of focal segmental glomerulosclerosis as well as other glomerular phenotypes. These risk variants are common in individuals of African ancestry but absent in other racial groups. Yet, the majority of individuals with two APOL1 risk alleles [high-risk (HR) genotype] do not have renal disease. It is critical to identify environmental and secondary genetic influences that, when combined with these alleles, lead to kidney disease. In a recent study of black children with glomerular disease enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) and Chronic Kidney Disease in Children Study (n = 104), we found that subjects with an HR genotype had a 4.6-fold increase in the odds of preterm birth as compared to those with a low risk (LR) genotype [odds ratio 4.6 (CI 1.4-15.5)]. There are known racial disparities in preterm birth, which itself is a known risk factor for chronic kidney disease and focal segmental glomerulosclerosis. Thus, we questioned whether an HR APOL1 genotype is associated with prematurity in the general African American population., Methods: We analyzed two publically available genetic datasets of preterm birth in African Americans, including 867 infants and 519 mothers from the Gene Environment Association Studies (GENEVA) study of preterm delivery and 960 mothers from the Boston Medical Center genome-wide association study of preterm birth. We performed multivariable analyses testing for association between HR APOL1 and birth outcomes., Results: In both studies, there was no association between HR APOL1 in mothers and prematurity, gestational age or birthweight. Additionally, in the GENEVA study, we saw no association between infant HR APOL1 and prematurity, gestational age or birthweight., Conclusion: From these data, we conclude that the previously observed association between HR APOL1 and prematurity is specific to those with glomerular disease, suggesting prematurity may act as an additional risk factor in APOL1-associated renal disease., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

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., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)