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Nephrol Dial Transplant. 2016 Feb;31(2):262-9. doi: 10.1093/ndt/gfv342. Epub 2015 Sep 28.

Genetic loci associated with renal function measures and chronic kidney disease in children: the Pediatric Investigation for Genetic Factors Linked with Renal Progression Consortium.

Author information

1
Renal Division, Department of Internal Medicine, Medical Center, University of Freiburg, Freiburg im Breisgau, Germany.
2
Division of Pediatric Nephrology, University of New Mexico Children's Hospital, Albuquerque, NM, USA.
3
Division of Pediatric Nephrology, University Medical Center Heidelberg, Heidelberg, Germany.
4
Division of Epidemiology, Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA.
5
Faculty of Medicine, Ege University, Izmir, Turkey.
6
Department of Pediatric Nephrology, Hannover Medical School, Hannover, Germany.
7
University of Manitoba, Winnipeg, Manitoba, Canada.
8
Charite Universitätsmedizin Berlin, Berlin, Germany.
9
Departments of Pediatrics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Childrens Hospital of Philadelphia, Philadelphia, PA, USA.
10
Division of Pediatric Nephrology, Children's Mercy Hospital, Kansas City, MO, USA.
11
Renal Division, Department of Internal Medicine, Medical Center, University of Freiburg, Freiburg im Breisgau, Germany Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Abstract

BACKGROUND:

Chronic kidney disease (CKD) in children is characterized by rapid progression and a high incidence of end-stage renal disease and therefore constitutes an important health problem. While unbiased genetic screens have identified common risk variants influencing renal function and CKD in adults, the presence and identity of such variants in pediatric CKD are unknown.

METHODS:

The international Pediatric Investigation for Genetic Factors Linked with Renal Progression (PediGFR) Consortium comprises three pediatric CKD cohorts: Chronic Kidney Disease in Children (CKiD), Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CRF in Pediatric Patients (ESCAPE) and Cardiovascular Comorbidity in Children with CKD (4C). Clean genotype data from > 10 million genotyped or imputed single-nucleotide polymorphisms (SNPs) were available for 1136 patients with measurements of serum creatinine at study enrollment. Genome-wide association studies were conducted to relate the SNPs to creatinine-based estimated glomerular filtration rate (eGFR crea) and proteinuria (urinary albumin- or protein-to-creatinine ratio ≥ 300 and ≥ 500 mg/g, respectively). In addition, European-ancestry PediGFR patients (cases) were compared with 1347 European-ancestry children without kidney disease (controls) to identify genetic variants associated with the presence of CKD.

RESULTS:

SNPs with suggestive association P-values < 1 × 10(-5) were identified in 10 regions for eGFR crea, four regions for proteinuria and six regions for CKD including some plausible biological candidates. No SNP was associated at genome-wide significance (P < 5 × 10(-8)). Investigation of the candidate genes for proteinuria in adults from the general population provided support for a region on chromosome 15 near RSL24D1/UNC13C/RAB27A. Conversely, targeted investigation of genes harboring GFR-associated variants in adults from the general population did not reveal significantly associated SNPs in children with CKD.

CONCLUSIONS:

Our findings suggest that larger collaborative efforts will be needed to draw reliable conclusions about the presence and identity of common variants associated with eGFR, proteinuria and CKD in pediatric populations.

KEYWORDS:

genetic epidemiology; genome-wide association study; glomerular filtration rate; pediatric chronic kidney disease; proteinuria

PMID:
26420894
PMCID:
PMC4829056
DOI:
10.1093/ndt/gfv342
[Indexed for MEDLINE]
Free PMC Article

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