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

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.

Renal and Cardiovascular Morbidities Associated with APOL1 Status among African-American and Non-African-American Children with Focal Segmental Glomerulosclerosis

“…Body mass index (BMI) was significantly higher among the HR APOL1 children ( p  < 0.001), and this group had a much higher proportion of obesity (BMI > 85th percentile adjusted for age and gender; 48 vs. 19%, p  = 0.01). Consistent with previously published reports (15), children with HR APOL1 had a higher prevalence of premature birth than children with LR APOL1 (29 vs. 5%, p  = 0.011), but this difference was not observed for low birth weight or small for gestational age.…”

“…In the CKiD cohort, the HR APOL1 genotype was associated with the glomerular phenotype in children younger than previously reported; previous studies have established that APOL1 -associated FSGS is characterized by a tendency to present between ages 15 and 39 years old (7) and in FSGS-CT with median age 17 years (13, 23) (8). The median age of FSGS onset among HR children was 12 years in CKiD, which was older than other LR children with FSGS, a finding previously reported alongside the NEPTUNE children with nephrotic syndrome (15). Additionally, this study found a higher prevalence of prematurity among those with HR APOL1 compared to AA and non-AA children with FSGS, similar to findings with NEPTUNE that employed a different reference group, suggesting that the prematurity effect extends to non-AA children.…”

“…LVH is common among hypertensive adults and children with CKD and is more common among AA than in whites (13, 14). While a previous report of two pediatric cohorts representing children with CKD (CKiD) and nephrotic syndrome (Nephrotic Syndrome Study Network; NEPTUNE) showed similar APOL1 characteristics in terms of FSGS diagnosis and disease progression (15), the association of APOL1 and cardiovascular comorbidities in the presence of CKD has not been explored. The purpose of this study was to extend previous findings (15), to characterize the distribution of APOL1 risk alleles in the CKiD cohort and, by comparing children with an underlying FSGS cause of CKD, to describe the prevalence of cardiorenal phenotypes and markers of disease severity associated with the HR APOL1 genotype.…”

Racial differences in renal replacement therapy initiation among children with a nonglomerular cause of chronic kidney disease

“…One recently identified cause among adults and children is the high risk APOL1 genotype [9–12], which is prevalent in about 13% of the AA population [10] and is associated with focal segmental glomerulosclerosis [12] and increased incidence of ESRD. Other research has shown that low SES, lack of social support, perceptions of poor treatment by medical professionals and a lack of knowledge of renal disease and treatment contribute to worse outcomes among AA adults, and a lower likelihood of kidney transplant referral [13–15].…”

“…Since AA race is strongly related to glomerular disease due to the APOL1 genotype [12,20], and glomerular disease is related to different disease trajectories than non-glomerular causes [21], we restricted to children with a non-glomerular cause of CKD (comprising most of the pediatric CKD population [22–24]) in the Chronic Kidney Disease in Children (CKiD) study and considered free of the high risk APOL1 genotype. A primary challenge in characterizing racial differences is accounting for the confounding effects of SES [25–27].…”