Long-Term Transplantation Outcomes in Patients With Primary Hyperoxaluria Type 1 Included in the European Hyperoxaluria Consortium (OxalEurope) Registry

Elisabeth L Metry; Sander F Garrelfs; Hessel Peters-Sengers; Sally-Anne Hulton; Cecile Acquaviva; Justine Bacchetta; Bodo B Beck; Laure Collard; Georges Deschênes; Casper Franssen; Markus J Kemper; Graham W Lipkin; Giorgia Mandrile; Nilufar Mohebbi; Shabbir H Moochhala; Michiel J S Oosterveld; Larisa Prikhodina; Bernd Hoppe; Pierre Cochat; Jaap W Groothoff; OxalEurope Consortium

doi:10.1016/j.ekir.2021.11.006

Long-Term Transplantation Outcomes in Patients With Primary Hyperoxaluria Type 1 Included in the European Hyperoxaluria Consortium (OxalEurope) Registry

Kidney Int Rep. 2021 Nov 26;7(2):210-220. doi: 10.1016/j.ekir.2021.11.006. eCollection 2022 Feb.

Authors

Elisabeth L Metry¹, Sander F Garrelfs¹, Hessel Peters-Sengers², Sally-Anne Hulton³, Cecile Acquaviva⁴, Justine Bacchetta⁵, Bodo B Beck^{6

7}, Laure Collard⁸, Georges Deschênes⁹, Casper Franssen¹⁰, Markus J Kemper¹¹, Graham W Lipkin¹², Giorgia Mandrile^{13

14}, Nilufar Mohebbi¹⁵, Shabbir H Moochhala¹⁶, Michiel J S Oosterveld¹, Larisa Prikhodina¹⁷, Bernd Hoppe¹⁸, Pierre Cochat⁵, Jaap W Groothoff¹; OxalEurope Consortium

Affiliations

¹ Department of Pediatric Nephrology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
² Center for Experimental and Molecular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
³ Department of Nephrology, Birmingham Women's and Children's Hospital NHS Foundation Trust, Birmingham, UK.
⁴ Service de Biochimie et Biologie Moléculaire, UM Pathologies Héréditaires du Métabolisme et du Globule Rouge, Hospices Civils de Lyon, France.
⁵ Centre de Référence des Maladies Rares Néphrogones, Hospices Civils de Lyon & Université Claude-Bernard Lyon, Lyon, France.
⁶ Institute of Human Genetics, Center for Molecular Medicine Cologne, University Hospital of Cologne, Cologne, Germany.
⁷ Center for Rare and Hereditary Kidney Disease Cologne, University Hospital of Cologne, Cologne, Germany.
⁸ Department of Pediatric Nephrology, Centre Hospitalier Universitaire Liège, Liège, Belgium.
⁹ Department of Pediatric Nephrology, Assistance Publique-Hôpitaux de Paris Robert-Debré, University of Paris, Paris, France.
¹⁰ Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
¹¹ Division of Pediatric Nephrology, University Children's Hospital, Hamburg, Germany.
¹² Department of Nephrology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
¹³ Medical Genetics Unit, Department of Clinical and Biological Sciences, University of Torino, Orbassano, Italy.
¹⁴ Thalassemia Unit, San Luigi University Hospital, Orbassano, Italy.
¹⁵ Division of Nephrology, University Hospital Zurich, Zurich, Switzerland.
¹⁶ UCL Department of Renal Medicine, Royal Free Hospital, London, UK.
¹⁷ Department of Inherited and Acquired Kidney Diseases, Research and Clinical Institute for Pediatrics, Pirogov Russian National Research Medical University, Moscow, Russia.
¹⁸ Department of Pediatric Nephrology, Children's Hospital of the University of Bonn, Bonn, Germany.

Abstract

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.

Keywords: combined liver-kidney transplantation; graft survival; primary hyperoxaluria; sequential liver-kidney transplantation.