Abstract
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. 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. 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. 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.
Highlights
Chronic kidney disease (CKD) is an important global health problem [1]
Our findings suggest that larger collaborative efforts will be needed to draw reliable conclusions about the presence and identity of common variants associated with estimated GFR (eGFR), proteinuria and CKD in pediatric populations
Differences in baseline glomerular filtration rate (GFR), serum creatinine and cystatin C as well as the proportion of proteinuric children were consistent with differences in study-specific inclusion criteria
Summary
Chronic kidney disease (CKD) is an important global health problem [1]. uncommon in children [2,3,4], CKD in this population is associated with increased risk for poor growth, cardiovascular disease and mortality [5,6,7]. Genome-wide association studies (GWAS) were used successfully to identify common genetic variants associated with measures of renal function and CKD in population-based studies [12,13,14,15,16,17] as well as with specific kidney diseases such as IgA nephropathy [18, 19] and membranous nephropathy [20]. Chronic kidney disease (CKD) in children is characterized by rapid progression and a high incidence of end-stage renal disease and constitutes an important health problem. The aim of the present study is to evaluate the effectiveness of seasonal influenza vaccination in reducing morbidity and mortality in incident end-stage renal disease patients on PD. From Taiwan’s National Health Insurance Research Database, we identified 2089 incident PD patients with seasonal influenza vaccination and 2089 propensity score matched incident PD patients without the vaccination during
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