Abstract: SA-PO604
Genetic Mutation Type and Cerebral Aneurysm Screening in Patients with ADPKD
Session Information
- Cystic Kidney Diseases: Genetic Causes, Modifiers, and Extrarenal Manifestations
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Cystic
Authors
- Ahn, Noella, Royal Free London NHS Foundation Trust, London, United Kingdom
- Preka, Evgenia, Paris Centre de Recherche Cardiovasculaire, Paris, Île-de-France, France
- Mulligan, Joshua Ken, University College London, London, United Kingdom
- Gale, Daniel P., University College London, London, United Kingdom
Background
Subarachnoid haemorrhage (SAH) is a devastating complication of Autosomal Dominant Polycystic Kidney Disease (ADPKD) due to increased rate of intracranial aneurysm (IA) formation in this population compared to the general population. The cause of IA formation is thought to be due to PKD1 and PKD2 gene mutation however, genetic risk factors or a geneotype-phenotype relationships are unclear unlike the correlation seen in renal manifestations of ADPKD. We report outcomes of our targeted screening of patients with personal or positive family history of IA or SAH with a five-yearly scans at a single large tertiary centre, alongside their genetic variants, to identify genetic risk factors or the presence of genotype-phenotype relationships in IA formation.
Methods
A retrospective review of 701 ADPKD patients in Royal Free Hospital between January 2012 to October 2022. Their medical records were reviewed for the development of IA, SAH, adherence to screening policy and their genetic tests.
Results
Of the 701 patients, 127 (18.1%) underwent screening as per the local guideline. 12 (1.7%) were eligible for screening but had not been screened. Within those screened, 21 (16.5%) had IA with zero SAH in this group. Of those unscreened, 8 (1.4%) had IA and 17 (3.0%) had SAH. Of the 701, 499 (71.2%) had genetic tests with clinically diagnostic variants in PKD1 in 260 (52.1%) with 169 truncating mutations, PKD2 in 102 (20.4%) with 78 truncating mutations, other genes in 78 (15.6%) and no reportable findings in 59 (11.8%). In 46 patients with IA or SAH, 33 (71.7%) had genetic tests of whom 21 (63.6%) had PKD1 which 13 were truncating, 6 (18.2%) had PKD2 which 4 were truncating, 6 (18.2%) had no genetic variants reported. These figures did not differ significantly from the overall patient cohort. 11 (8.6%) of the 127 screened patients received intervention for their aneurysms.
Conclusion
Cerebral aneurysm screening is a key part of ADPKD management. Amongst the screened group, no SAH were observed, although this did not differ significantly from the event rate of the unscreened group. The lack of evidence of increased risk of IA or SAH in those with truncating PKD1 mutations suggest that the mechanism mediating this manifestation of ADPKD differs from the somatic loss of the normal allele that is thought to be important in kidney cyst formation and hence renal failure in ADPKD.