Tuesday May 07, 2019 from 08:00 to 09:30
Outcome after isolated or combined liver or kidney transplantation in patients with methylmalonic acidemia: A multicenter registry analysis
Luca Dello Strologo1, Marco Spada1, Carlo Dionisi Vici1, Noel Knops3, Elena Levtchenko3, Lars Wennberg4, James Squires5, George Mazariegos5, Mohan Shenoy6, Sangeet Sidhu6, Lorenzo D'Antiga7, Laura Martelli7, Anna Kristina Bjerre 8, Trine Tangeras8, Lyndsay A. Harshman9, Stephen D Marks10, Pierluigi Calvo11, Marco Spada11, Waldo Conception12, Friederike Horster2, Burkhard Tönshoff2.
1Pediatric, Bambino Gesu Children's Hospital, Rome, Italy; 2Department of Pediatrics I, University Children’s Hospital, Heidelberg, Germany; 3Department of Pediatric Nephrology, University of Leuven, Leuven, Belgium; 4Departement of Transplantation Surgery, Karolinska University Hospital , Stockholm, Sweden; 5Pediatric Hepatogy and Transplant Surgery, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA, United States; 6Pediatric Nephrology, Royal Manchester Children’s Hospital, , Manchester, United Kingdom; 7Paediatric Transplantation, Hospital Papa Giovanni XXIII, Bergamo, Italy; 8Dep of Paediatric and Adoles Med, Oslo University Hospital, Oslo, Norway; 9University of Iowa, University of Iowa, Iowa, IA, United States; 10University College London, Great Ormond Street Institute of Child Health, London, United Kingdom; 11Department of Pediatrics, University of Torino, Turin, Italy; 12Division of Transplantation, Stanford University School of Medicine , Stanford, CA, United States
Introduction: Methylmalonic acidemia (MMA) is a rare inherited metabolic disorder characterized by the accumulation of methylmalonic acid, leading to recurrent metabolic decompensation episodes and to chronic organ injury. Recently, there has been a growing interest in organ transplantation approaches: kidney transplantation (KTx) corrects renal failure but only partially restores the enzyme activity which is better obtained by liver (LTx) or combined liver/kidney transplant (LKTx). A consensus on the optimal transplant strategy is lacking. Our aim was to compare in a large multicenter study the results of different transplant approaches in patients affected by MMA.
Material and methods: Within centers of the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) Registry and additional centers both in the US and in Europe (thanks to the joint effort of ESPN and MidWest consortium) we collected retrospective clinical and biochemical outcome data from transplanted patients with MMA from the year 2000 to present.
Results: So far, 58 patients were registered. Currently, data are available for 34 patients: 19 with KTx, 7 with LTx and 8 with LKTx. Median age (years) at transplant was 13.6 for KTx, 2.5 for LTx and 8.2 for LKTx. Median pre-transplant plasma MMA was higher in patients with KTx (2572 µmol/L) than in LTx (599 µmol/L) or LKTx (836 µmol/L). Post-transplant MMA was evaluated at 1, 6 and 12 months (Figure). At 1 and 6 months, all patients had a clear reduction of plasma MMA, whereas at 12 months only KTx patients showed a negative trend with a return plasma MMA increase. LTx and LKTx patients maintained significantly lower MMA plasma levels.
At transplantation, eGFR in LTx and LKTx was 87 and 40 ml/min/1.73 m2. KTx patients were in advanced chronic renal failure. At month 12, renal function was still normal in LTx or LKTx (median eGFR 104 and 89 ml/min/1.73 m2), while in KTx it was only 49 ml/min/1.73 m2. At last follow-up, 21% of pts with KTx and 13% with LTx or LKTx were deceased. Neurological outcome at 1 year post-transplant was stable in all patients.
Conclusion: These data show a more pronounced and persistent post-transplant reduction of plasma MMA levels following LTx or LKTx compared to KTx alone. Graft and possibly patient survival is suboptimal following isolated KTx, where impaired graft function likely leads to reduction in renal filtration of MMA and lower intrarenal enzymatic activity, both of which increase MMA plasma levels driving further decline of renal function.