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

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

doi:10.3389/fped.2016.00122

Abstract

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. 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. 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. 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.

Highlights

African-Americans (AA) have higher rates of hypertension (HTN) and kidney disease compared to Americans of European descent [1]
A total of 891 children were enrolled in CKiD, of whom 199 (22%) were AA; Figure 1 presents the distributions of APOL1 genotypes and chronic kidney disease (CKD) diagnoses by race
Of these 59 children, 47% had a glomerular cause of CKD; 39% of these had a diagnosis of focal segmental glomerulosclerosis (FSGS)

Summary

Introduction

African-Americans (AA) have higher rates of hypertension (HTN) and kidney disease compared to Americans of European descent [1]. While studies in adult AA populations demonstrated strong recessive association of APOL1 G1 and G2 genetic variants with glomerular and vascular disease progression [7], there is limited information on its role in children with chronic kidney disease (CKD), for cardiovascular comorbidities. 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. 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

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