TY - JOUR
T1 - Long-Term Transplantation Outcomes in Patients With Primary Hyperoxaluria Type 1 Included in the European Hyperoxaluria Consortium (OxalEurope) Registry
AU - OxalEurope Consortium
AU - Metry, Elisabeth L.
AU - Garrelfs, Sander F.
AU - Peters-Sengers, Hessel
AU - Hulton, Sally Anne
AU - Acquaviva, Cecile
AU - Bacchetta, Justine
AU - Beck, Bodo B.
AU - Collard, Laure
AU - Deschênes, Georges
AU - Franssen, Casper
AU - Kemper, Markus J.
AU - Lipkin, Graham W.
AU - Mandrile, Giorgia
AU - Mohebbi, Nilufar
AU - Moochhala, Shabbir H.
AU - Oosterveld, Michiel J.S.
AU - Prikhodina, Larisa
AU - Hoppe, Bernd
AU - Cochat, Pierre
AU - Groothoff, Jaap W.
N1 - Funding Information: ELM, SFG, MJSO, and JWG have received an unconditional grant from both Alnylam Pharmaceuticals and Dicerna Pharmaceuticals, not related to this work. BH is a senior medical advisor at Dicerna Pharmaceuticals. SAH has received consultation fees and travel grants from Dicerna Pharmaceuticals and Alnylam Pharmaceuticals. Alnylam and Dicerna have provided an unconditional grant to the OxalEurope Registry. All the other authors declared no competing interests. Publisher Copyright: © 2021 International Society of Nephrology
PY - 2022/2
Y1 - 2022/2
N2 - Introduction: In primary hyperoxaluria type 1 (PH1), oxalate overproduction frequently causes kidney stones, nephrocalcinosis, and kidney failure. As PH1 is caused by a congenital liver enzyme defect, combined liver–kidney transplantation (CLKT) has been recommended in patients with kidney failure. Nevertheless, systematic analyses on long-term transplantation outcomes are scarce. The merits of a sequential over combined procedure regarding kidney graft survival remain unclear as is the place of isolated kidney transplantation (KT) for patients with vitamin B6-responsive genotypes. Methods: We used the OxalEurope registry for retrospective analyses of patients with PH1 who underwent transplantation. Analyses of crude Kaplan–Meier survival curves and adjusted relative hazards from the Cox proportional hazards model were performed. Results: A total of 267 patients with PH1 underwent transplantation between 1978 and 2019. Data of 244 patients (159 CLKTs, 48 isolated KTs, 37 sequential liver–KTs [SLKTs]) were eligible for comparative analyses. Comparing CLKTs with isolated KTs, adjusted mortality was similar in patients with B6-unresponsive genotypes but lower after isolated KT in patients with B6-responsive genotypes (adjusted hazard ratio 0.07, 95% CI: 0.01–0.75, P = 0.028). CLKT yielded higher adjusted event-free survival and death-censored kidney graft survival in patients with B6-unresponsive genotypes (P = 0.025, P < 0.001) but not in patients with B6-responsive genotypes (P = 0.145, P = 0.421). Outcomes for 159 combined procedures versus 37 sequential procedures were comparable. There were 12 patients who underwent pre-emptive liver transplantation (PLT) with poor outcomes. Conclusion: The CLKT or SLKT remains the preferred transplantation modality in patients with PH1 with B6-unresponsive genotypes, but isolated KT could be an alternative approach in patients with B6-responsive genotypes.
AB - Introduction: In primary hyperoxaluria type 1 (PH1), oxalate overproduction frequently causes kidney stones, nephrocalcinosis, and kidney failure. As PH1 is caused by a congenital liver enzyme defect, combined liver–kidney transplantation (CLKT) has been recommended in patients with kidney failure. Nevertheless, systematic analyses on long-term transplantation outcomes are scarce. The merits of a sequential over combined procedure regarding kidney graft survival remain unclear as is the place of isolated kidney transplantation (KT) for patients with vitamin B6-responsive genotypes. Methods: We used the OxalEurope registry for retrospective analyses of patients with PH1 who underwent transplantation. Analyses of crude Kaplan–Meier survival curves and adjusted relative hazards from the Cox proportional hazards model were performed. Results: A total of 267 patients with PH1 underwent transplantation between 1978 and 2019. Data of 244 patients (159 CLKTs, 48 isolated KTs, 37 sequential liver–KTs [SLKTs]) were eligible for comparative analyses. Comparing CLKTs with isolated KTs, adjusted mortality was similar in patients with B6-unresponsive genotypes but lower after isolated KT in patients with B6-responsive genotypes (adjusted hazard ratio 0.07, 95% CI: 0.01–0.75, P = 0.028). CLKT yielded higher adjusted event-free survival and death-censored kidney graft survival in patients with B6-unresponsive genotypes (P = 0.025, P < 0.001) but not in patients with B6-responsive genotypes (P = 0.145, P = 0.421). Outcomes for 159 combined procedures versus 37 sequential procedures were comparable. There were 12 patients who underwent pre-emptive liver transplantation (PLT) with poor outcomes. Conclusion: The CLKT or SLKT remains the preferred transplantation modality in patients with PH1 with B6-unresponsive genotypes, but isolated KT could be an alternative approach in patients with B6-responsive genotypes.
KW - combined liver-kidney transplantation
KW - graft survival
KW - primary hyperoxaluria
KW - sequential liver-kidney transplantation
UR - http://www.scopus.com/inward/record.url?scp=85120821615&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ekir.2021.11.006
DO - https://doi.org/10.1016/j.ekir.2021.11.006
M3 - Article
C2 - 35155860
SN - 2468-0249
VL - 7
SP - 210
EP - 220
JO - Kidney International Reports
JF - Kidney International Reports
IS - 2
ER -