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

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

Journal: Molecular genetics and metabolism 2022;137(3):265-272

PMID: 36240580

Full Text on Elsevier Science View on PubMed

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 mut-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 m, in LTx 99.8 ± 29.9 mL/min/1.73 m, and in LKTx 31.5 ± 21.2 mL/min/1.73 m. At month 12 posttransplant, mean eGFR in KTx (62.3 ± 30.3 mL/min/1.73 m) was 33.4% lower than in LTx (93.5 ± 18.3 mL/min/1.73 m; P = 0.0053) and 25.4% lower than in LKTx (83.5 ± 26.9 mL/min/1.73 m; 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.

Address: Nephrology, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.; Surgery, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.; Metabolism, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.; Epidemiology, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.; University of Minnesota Children's Hospital, USA.; Department of Paediatric and Adolescent Medicine, Oslo University Hospital, Norway; Institute of Clinical Medicine, University of Oslo, Norway.; Hopital Necker - Enfant Malades, MARHEA, Institut Imagine, Université Paris Cité, Paris, France.; Department of Pediatrics, University of Torino, Turin, Italy.; Paediatric Hepatology, Gastroenterology and Transplantation Hospital Papa Giovanni XXIII, Bergamo, Italy.; University of Iowa, USA.; Department of Pediatrics I, University Children's Hospital, Heidelberg, Germany.; Department of Pediatric Nephrology and Transplantation, New Children's Hospital Helsinki, Finland.; Department of Pediatric Nephrology & Growth and Regeneration, University Hospitals Leuven & University of Leuven, Belgium.; Division of Transplantation, Stanford University School of Medicine, USA.; NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London Great Ormond Street Institute of Child Health, London, UK.; Pediatric Transplant Surgery, UPMC Children's Hospital of Pittsburgh, USA.; Pediatric Nephrology, Dialysis and Transplantation Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico Milan, Italy.; Pediatric Nephrology, Royal Manchester Children's Hospital, UK.; Department of Paediatric and Adolescent Medicine, Oslo University Hospital, Norway.; Pediatrics, Birmingham Children's Hospital NHS Foundation Trust, UK.; Department of Transplantation Surgery, Karolinska University Hospital Stockholm, Sweden.; Department of Pediatrics I, University Children's Hospital, Heidelberg, Germany. Electronic address: [email protected].

DOI: 10.1016/j.ymgme.2022.09.010