P252
Diagnostic genetic testing in ADPKD may increase living related kidney transplantation
RJ Simms1, D Travis2, M Durkie2, ACM Ong3
1
Freeman Hospital, Freeman Road, Newcastle upon Tyne, NE7 7DN; 2Sheffield
Diagnostic Genetics Service, Sheffield Children’s NHS Foundation Trust, S10 2TH;
3
Kidney Genetics Group, Academic Unit of Nephrology, University of Sheffield, S10
2RX
Background: Autosomal dominant polycystic kidney disease (ADPKD) is the
commonest inherited kidney condition and approximately 50% of affected individuals
will progress to established renal failure. Data from the UK renal registry in 2012
reported that ADPKD accounts for 9.7% of all adults requiring renal replacement
therapy (RRT, dialysis or transplantation). Renal transplantation is the optimal
modality of RRT because it confers improved patient survival, particularly living
kidney donation which enables pre-emptive transplantation. However potential living
related kidney donors with a family history of ADPKD require careful exclusion of a
personal diagnosis of ADPKD. The British Transplantation Society (BTS) guidelines
for assessment of living kidney donors recommend consideration of genetic testing for
ADPKD in at-risk kidney donors with equivocal renal imaging or normal imaging at a
younger age (<40 years). We report our experience of the utility of diagnostic genetic
testing for ADPKD in probands and predictive testing in potential living related kidney
donors.
Methods: Clinicians or geneticists referred probands with ADPKD for genetic testing
including sequencing of PKD1 or PKD2, and if no mutation was identified, multiplex
ligation dependent probe amplification (MLPA) analysis to detect a large deletion or
duplication in PKD1 or PKD2. Recommendations for the extent of analyses were made
by the diagnostic genetic service based on clinical details and the results of initial
analysis. Predictive testing was only performed if a highly likely pathogenic mutation
was identified in the proband. The referring clinical team were contacted to ascertain
further detailed information including: family history, imaging results for potential
donors, whether transplantation proceeded and the perceived utility of the genetic
diagnostic service.
Results: 19 probands and potential living related kidney donors were referred for
genetic testing between May 2010 and October 2012. Further clinical data and whether
transplantation proceeded were unavailable in 5 families. Predictive genetic testing
enabled 18 potential living related kidney donors to be identified (negative for the
familial mutation). 4 living related kidney transplants occurred. 10 further living related
kidney donations did not occur, despite negative genetic testing because of
donor/recipient choice or remaining concerns regarding renal imaging results.
Conclusion This is the largest reported series of the role of predictive testing for
ADPKD in living related kidney donor transplantation assessment. Predictive testing
has the potential to facilitate increased living kidney transplantation in ADPKD
pedigrees particularly in at-risk donors of a young age or in whom renal imaging is
inconclusive.