Kidney disease and organ transplantation in methylmalonic acidaemia

Abstract

Objectives MMA is associated with chronic tubulointerstitial nephritis and a progressive decline in GFR. Optimal management of these children is uncertain. Our objectives were to document the pre‐, peri‐, and post‐transplant course of all children with MMA who underwent liver or combined liver‐kidney transplant in our centers. Design and methods Retrospective chart review of all cases of MMA who underwent organ transplantation over the last 10 years. Results Five children with MMA underwent liver transplant (4/5) and combined liver‐kidney transplant (1/5). Three were Mut0 and two had a cobalamin B disorder. Four of five were transplanted between ages 3 and 5 years. Renal dysfunction prior to transplant was seen in 2/5 patients. Post‐transplant (one liver transplant and one combined transplant) renal function improved slightly when using creatinine‐based GFR formula. We noticed in 2 patients a big discrepancy between creatinine‐ and cystatin C‐based GFR calculations. One patient with no renal disease developed renal failure post–liver transplantation. Serum MMA levels have decreased in all to <300 μmol/L. Four patients remain on low protein diet, carnitine, coenzyme Q, and vitamin E post‐transplant. Conclusions MMA is a complex metabolic disorder. Renal disease can continue to progress post–liver transplant and close follow‐up is warranted. More research is needed to clarify best screening GFR method in patients with MMA. Whether liver transplant alone, continued protein restriction, or the addition of antioxidants post‐transplant can halt the progression of renal disease remains unclear.

Guidelines for the diagnosis and management of methylmalonic acidaemia and propionic acidaemia: First revision

“…In transplanted MMA and PA patients diet normalisation, 42,84,89,90,93,94,103,104,112‐115 liberalisation or increased protein intake 75,76,78,80,83,88,91,96‐98,100,102,116‐118 or continuation of dietary restrictions 85,87,119 were all applied following transplantation. Liberalised and continuous diet both led to metabolically stable situations without acute decompensation 89,103 .…”

“…110 Organ transplantation of patients in acute metabolic decompensation should be avoided, as the procedure itself has the potential to cause further decompensation. 111 In transplanted MMA and PA patients diet normalisation, 42,84,89,90,93,94,103,104,[112][113][114][115] liberalisation or increased protein intake 75,76,78,80,83,88,91,[96][97][98]100,102,[116][117][118] or continuation of dietary restrictions 85,87,119 were all applied following transplantation. Liberalised and continuous diet both led to metabolically stable situations without acute decompensation.…”

“…95,117,118,183,184 Kidney transplant improves renal function shortly after transplantation and in some even for years (1.5 years up to 14 years) after transplantation, 54,85,88,179 but recurrence of nephropathy and renal failure has also been reported after kidney transplant. 47,185 After liver transplantation several patients showed normal renal function even up to 15 years after transplantation, 119,184 while others have or develop (progressive) renal failure after transplantation. 94,101,106,116,119 Liver transplantation seems not to correct an already dysfunctional kidney.…”

“…47,185 After liver transplantation several patients showed normal renal function even up to 15 years after transplantation, 119,184 while others have or develop (progressive) renal failure after transplantation. 94,101,106,116,119 Liver transplantation seems not to correct an already dysfunctional kidney. 97 In PA, one patient was reported with kidney transplant 17 years after liver transplant.…”

Nutritional Management and Biochemical Outcomes during the Immediate Phase after Liver Transplant for Methylmalonic Acidemia

“…This was similar for our patients, and their methylmalonic acid levels were still much higher than the normal reference range. Due to the nephrotoxicity of methylmalonic acid, renal disease can continue to progress even after liver transplant, and plasma methylmalonic acid could rise as GFR declines [ 22 ]. In this setting, PFAA formula may need to be potentially reintroduced to reduce the methylmalonic acid level.…”