| Title: |
#3721 Pharmacogenetic analysis from exome data and pharmaco-clinico-biological co-interpretation enable personalized care in nephrology and kidney transplantation |
| Authors: |
Bensouna, Ilias; Deroche, Virginie; Ponce, Fanny; Hatz, Karl-Dietrich; Jauniaux, Nicolas; Benomar, Amina; Debrix, Isabelle; Federspiel, Florence; Raymond, Laure; Mesnard, Laurent |
| Source: |
Nephrology Dialysis Transplantation ; volume 40, issue Supplement_3 ; ISSN 0931-0509 1460-2385 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2025 |
| Description: |
Background and Aims Preemptive pharmacogenetic panel testing has been shown to reduce the incidence of clinically detectable side effects by 30%. At Sorbonne University, exome sequencing is routinely performed for adults with unknown nephropathy or genetically-suspected chronic kidney disease (CKD), offering not only molecular diagnosis but also underutilized pharmacogenetic insights. CKD patients, who are frequently polymedicated, could greatly benefit from pharmacogenetic data as treatment efficacy and safety are influenced by genetic factors. Method We analyzed pharmacogenetic profiles for 456 adult patients who underwent exome sequencing (Twist capture, Illumina NovaSeq6000, 2 × 150 bp) for unknown nephropathy. The analysis targeted 217 variants in 23 pharmacogenes following CPIC and DPWG guidelines. HLA-A and HLA-B loci were characterized using a dedicated exome pipeline. Star alleles translation and dosing guidelines were conducted using SONOGEN-XP (INTLAB AG) based on international recommendations. 68 patients received medication reconciliation and counseling to complete their current treatment list and related drug adverse effects to consider dosage adjustments or treatment modifications. 19 cases were reviewed in multidisciplinary consultation meetings (MCM). Results In-house pharmacogenetic analysis from exome data demonstrated complete concordance with reference samples from Get-RM and orthogonal methods (PCR amplification and LC-MS detection, Immucor for HLA profile study). 100% of patients had at least one actionable pharmacogene variant. Following MCM, all 19 patients received recommendations regarding drug dosing or contraindications, totaling 60 individualized recommendations. Relevant drugs affected by altered metabolism included tacrolimus (9/19), azathioprine (1/19), tramadol (6/19), clopidogrel (7/19), allopurinol (3/19), atorvastatin (5/19). Conclusion Pharmacogenetic analysis based on exome data is valuable for managing patients with chronic kidney disease, as it can prevent ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1093/ndt/gfaf116.0173 |
| Availability: |
https://doi.org/10.1093/ndt/gfaf116.0173; https://academic.oup.com/ndt/article-pdf/40/Supplement_3/gfaf116.0173/64834105/gfaf116.0173.pdf |
| Rights: |
https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model |
| Accession Number: |
edsbas.7B6DB56C |
| Database: |
BASE |