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

Robert P Woroniecki, Derek K Ng, Sophie Limou, Cheryl A Winkler, Kimberly J Reidy, Mark Mitsnefes, Matthew G Sampson, Craig S Wong, Bradley A Warady, Susan L Furth, Jeffrey B Kopp, Frederick J Kaskel, Robert P Woroniecki, Derek K Ng, Sophie Limou, Cheryl A Winkler, Kimberly J Reidy, Mark Mitsnefes, Matthew G Sampson, Craig S Wong, Bradley A Warady, Susan L Furth, Jeffrey B Kopp, Frederick J Kaskel

Abstract

Background and objectives: African-American (AA) children with focal segmental glomerulosclerosis (FSGS) have later onset disease that progresses more rapidly than in non-AA children. It is unclear how APOL1 genotypes contribute to kidney disease risk, progression, and cardiovascular morbidity in children.

Design setting participants and measurements: We examined the prevalence of APOL1 genotypes and associated cardiovascular phenotypes among children with FSGS in the Chronic Kidney Disease in Children (CKiD) study; an ongoing multicenter prospective cohort study of children aged 1-16 years with mild to moderate kidney disease.

Results: A total of 140 AA children in the CKiD study were genotyped. High risk (HR) APOL1 genotypes were present in 24% of AA children (33/140) and were associated with FSGS, p < 0.001. FSGS was the most common cause of glomerular disease in children with HR APOL1 (89%; 25/28). Of 32 AA children with FSGS, 25 (78%) had HR APOL1. Compared to children with low risk APOL1 and FSGS (comprising 36 non-AA and 7 AA), children with HR APOL1 developed FSGS at a later age, 12.0 (IQR: 9.5, 12.5) vs. 5.5 (2.5, 11.5) years, p = 0.004, had a higher prevalence of uncontrolled hypertension (52 vs. 33%, p = 0.13), left ventricular hypertrophy (LVH) (53 vs. 12%, p < 0.01), C-reactive protein > 3 mg/l (33 vs. 15%, p = 0.12), and obesity (48 vs. 19%, p = 0.01). There were no differences in glomerular filtration rate, hemoglobin, iPTH, or calcium-phosphate product.

Conclusion: AA children with HR APOL1 genotype and FSGS have increase prevalence of obesity and LVH despite a later age of FSGS onset, while adjusting for socioeconomic status. Treatment of obesity may be an important component of chronic kidney disease and LVH management in this population.

Keywords: FSGS; cardiovascular; children; chronic renal disease; left ventricular hypertrophy.

Figures

Figure 1
Figure 1
Distribution of CKiD children by race [African-American (AA) vs. non-African-American (non-AA)], APOL1 genotypes, and CKD diagnoses [glomerular disease (Glom), non-glomerular disease (Non-Glom), focal segmental glomerulosclerosis (FSGS)] All genotyped non-AA (N = 37) were found to have LR APOL1 status, providing a justification for classifying non-AA children as low risk.
Figure 2
Figure 2
Percentile boxplots of longitudinal GFR changes based on individual regression equations, expressed as percent change per year, by APOL1 risk and race. A total of six non-AA LR participants, two AA LR participants, and two AA HR participants only contributed one GFR measurement and were not included in this analysis.

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