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

Derek K. Ng, Catherine C. Robertson, Robert P. Woroniecki, Sophie Limou, Christopher E. Gillies, Kimberly J. Reidy, Cheryl A. Winkler, Sangeeta Hingorani, Keisha L. Gibson, Rebecca Hjorten, Christine B. Sethna, Jeffrey B. Kopp, Marva Moxey-Mims, Susan L. Furth, Bradley A. Warady, Matthias Kretzler, John R. Sedor, Frederick J. Kaskel, Matthew G. Sampson

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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 m2; NEPTUNE: 74 versus 94 mL/min/1.73 m2). 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.

Original languageEnglish (US)
Pages (from-to)983-990
Number of pages8
JournalNephrology Dialysis Transplantation
Volume32
Issue number6
DOIs
StatePublished - Jan 1 2017

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Apolipoproteins
Nephrotic Syndrome
Chronic Renal Insufficiency
African Americans
Cohort Studies
Genotype
Focal Segmental Glomerulosclerosis
Glomerular Filtration Rate
Premature Birth
Natural History
Age of Onset

Keywords

  • Apol1
  • Epidemiology
  • Fsgs
  • Nephrotic syndrome
  • Pediatrics

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

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. / 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.

In: Nephrology Dialysis Transplantation, Vol. 32, No. 6, 01.01.2017, p. 983-990.

Research output: Contribution to journalArticle

Ng, DK, Robertson, CC, Woroniecki, RP, Limou, S, Gillies, CE, Reidy, KJ, Winkler, CA, Hingorani, S, Gibson, KL, Hjorten, R, Sethna, CB, Kopp, JB, Moxey-Mims, M, Furth, SL, Warady, BA, Kretzler, M, Sedor, JR, Kaskel, FJ & Sampson, MG 2017, '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', Nephrology Dialysis Transplantation, vol. 32, no. 6, pp. 983-990. https://doi.org/10.1093/ndt/gfw061
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. / 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. In: Nephrology Dialysis Transplantation. 2017 ; Vol. 32, No. 6. pp. 983-990.
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abstract = "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 m2; NEPTUNE: 74 versus 94 mL/min/1.73 m2). 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.",
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TY - JOUR

T1 - APOL1-Associated glomerular disease among African-American children

T2 - A collaboration of the chronic kidney disease in children (CKiD) and nephrotic syndrome study network (NEPTUNE) cohorts

AU - Ng, Derek K.

AU - Robertson, Catherine C.

AU - Woroniecki, Robert P.

AU - Limou, Sophie

AU - Gillies, Christopher E.

AU - Reidy, Kimberly J.

AU - Winkler, Cheryl A.

AU - Hingorani, Sangeeta

AU - Gibson, Keisha L.

AU - Hjorten, Rebecca

AU - Sethna, Christine B.

AU - Kopp, Jeffrey B.

AU - Moxey-Mims, Marva

AU - Furth, Susan L.

AU - Warady, Bradley A.

AU - Kretzler, Matthias

AU - Sedor, John R.

AU - Kaskel, Frederick J.

AU - Sampson, Matthew G.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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 m2; NEPTUNE: 74 versus 94 mL/min/1.73 m2). 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.

AB - 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 m2; NEPTUNE: 74 versus 94 mL/min/1.73 m2). 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.

KW - Apol1

KW - Epidemiology

KW - Fsgs

KW - Nephrotic syndrome

KW - Pediatrics

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DO - 10.1093/ndt/gfw061

M3 - Article

VL - 32

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EP - 990

JO - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

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