Abstract: SA-PO680
Pediatric and Adult Kidneys Have Largely Similar Gene Expression in CKD and Non-CKD
Session Information
- Pediatric Nephrology - 2
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1900 Pediatric Nephrology
Authors
- Sinsakul, Marvin, AstraZeneca, Gaithersburg, Maryland, United States
- Ryaboshapkina, Maria, AstraZeneca, Gothenburg, Sweden
- Acoba, Dianne, AstraZeneca, Gothenburg, Sweden
- Breitenstein, Stefanie, Bayer AG, Pharmaceuticals, Wuppertal, Germany
- Berger, Mario, Bayer AG, Pharmaceuticals, Wuppertal, Germany
- Reznichenko, Anna, AstraZeneca, Gothenburg, Sweden
Background
Understanding the molecular similarities between kidney diseases in children and adults is important for pediatric drug development. Here, we assessed age-related changes in kidney gene expression.
Methods
We surveyed public pediatric transcriptomics data and analyzed 5 cohorts (non-diseased GSE11024, GSE70503, GSE147451, mostly glomerular CKD GSE104954 and GSE68127). Differential expression analysis was adjusted for batch as appropriate and APOL1 risk group in GSE68127. Genes with false discovery rate < 5% were considered significant. CKD molecular category (Reznichenko et al. 2024 PMID38286178) was predicted for children in GSE68127.
Results
In total, the 5 cohorts included 53 children from 0 to 17 and 388 adults from 18 to 90 years. Pediatric and adult kidney samples did not clearly segregate on principal component analysis (PCA), neither in CKD nor in non-CKD cohorts (Fig 1A). We detected no to minimal differential expression changes, which constituted < 0.5% of measured genes in every cohort (Fig 1B). All adult CKD molecular categories were detected among children, with relative proportions and technical mapping quality similar to the adult CKD (Fig 1C).
Conclusion
Age per se had minimal effect on kidney gene expression. Instead, the gene expression profile in CKD was driven by molecular pathophysiology of CKD.
Fig. 1. Representative results in tubulointerstitium. 26 children (6-17 years) and 29 adults (18-74 years) with nephrotic syndrome GSE68127. A. PCA. B. Differential expression (significant genes in orange). C. Children mapped on to the adult CKD molecular categorization map.