Renal outcome and plasma methylmalonic acid levels after isolated or combined liver or kidney transplantation in patients with methylmalonic acidemia: A multicenter analysis

Luca Dello Strologo, Marco Spada, Carlo Dionisi Vici, Marta Ciofi Degli Atti, Michelle Rheault, Anna Kristina Bjerre, Olivia Boyer, Pier Luigi Calvo, Lorenzo D'Antiga, Lyndsay A. Harshman, Friederike Hörster, Stefan Kölker, Timo Jahnukainen, Noël Knops, Pauline Krug, Kai Krupka, Angela Lee, Elena Levtchenko, Stephen D. Marks, Jelena StojanovicLaura Martelli, George Mazariegos, Giovanni Montini, Mohan Shenoy, Sangeet Sidhu, Trine Tangeras, Sara Testa, Suresh Vijay, Katarzyna Wac, Lars Wennberg, Waldo Concepcion, Sven F. Garbade, Burkhard Tönshoff

Research output: Contribution to journalArticlepeer-review

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Abstract

Background: Methylmalonic acidemia (MMAemia) is characterized by accumulation of methylmalonic acid (MMA) in all body tissues. To minimize disease-related complications, isolated kidney (KTx), liver (LTx) or combined liver-kidney transplantation (LKTx) have been suggested. However, the impact of these different transplant strategies on outcome are unclear. Methods: In this multicenter retrospective observational study, we compared plasma MMA levels and estimated glomerular filtration rate (eGFR) data of 83 patients. Sixty-eight patients (82%) had a mut0-type MMAemia, one patient had a mut-type MMAemia, and seven (7.3%) had an inherited defect in cobalamin metabolism (cblA- or cblB-type MMAemia). Median observation period was 3.7 years (0–15.1 years). Results: Twenty-six (31%) patients underwent KTx, 24 (29%) LTx and 33 (40%) LKTx. Posttransplant, mean plasma MMA concentration significantly decreased in all three cohorts; but at month 12, plasma MMA in KTx (1372 ± 1101 μmol/L) was 7.8-fold higher than in LTx (176 ± 103 μmol/L; P < 0.001) and 6.4-fold higher than in LKTx (215 ± 110 μmol/L; P < 0.001). Comparable data were observed at month 24. At time of transplantation, mean eGFR in KTx was 18.1 ± 24.3 mL/min/1.73 m2, in LTx 99.8 ± 29.9 mL/min/1.73 m2, and in LKTx 31.5 ± 21.2 mL/min/1.73 m2. At month 12 posttransplant, mean eGFR in KTx (62.3 ± 30.3 mL/min/1.73 m2) was 33.4% lower than in LTx (93.5 ± 18.3 mL/min/1.73 m2; P = 0.0053) and 25.4% lower than in LKTx (83.5 ± 26.9 mL/min/1.73 m2; P = 0.0403). Conclusions: In patients with isolated MMAemia, LTx and LKTx lead to markedly lower plasma MMA levels during the first 2 years posttransplant than KTx and are associated with a better preservation of kidney function. LTx should therefore be part of the transplant strategy in MMAemia.

Original languageEnglish (US)
Pages (from-to)265-272
Number of pages8
JournalMolecular Genetics and Metabolism
Volume137
Issue number3
DOIs
StatePublished - Nov 2022

Bibliographical note

Funding Information:
We thank the European Society for Paediatric Nephrology and the Midwest Pediatric Nephrology consortium for their support with patient recruitment. Trine Tangeraas and Stefan Kölker are members of the European Reference Network for Rare Hereditary Metabolic Disorders (MetabERN). The authors gratefully acknowledge the funding of the CERTAIN Registry by a grant from the Dietmar Hopp Stiftung , the European Society for Paediatric Nephrology (ESPN) , The German Society for Pediatric Nephrology (GPN) , and by grants from the pharmaceutical companies Astellas and Novartis .

Funding Information:
We thank the European Society for Paediatric Nephrology and the Midwest Pediatric Nephrology consortium for their support with patient recruitment. Trine Tangeraas and Stefan Kölker are members of the European Reference Network for Rare Hereditary Metabolic Disorders (MetabERN). The authors gratefully acknowledge the funding of the CERTAIN Registry by a grant from the Dietmar Hopp Stiftung, the European Society for Paediatric Nephrology (ESPN), The German Society for Pediatric Nephrology (GPN), and by grants from the pharmaceutical companies Astellas and Novartis.

Publisher Copyright:
© 2022 Elsevier Inc.

Keywords

  • Combined liver-kidney transplantation
  • Estimated glomerular filtration rate
  • Kidney transplantation
  • Liver transplantation
  • Methylmalonic acid
  • Methylmalonic acidemia

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