Clinical Practice Recommendations on Kidney Management in Methylmalonic Acidemia: an Expert Consensus Statement From ERKNet and MetabERN

Abstract

Methylmalonic acidemias (MMA) are rare inherited metabolic diseases with multi-organ involvement. Chronic kidney disease (CKD) is a common complication, leading to kidney failure, dialysis, and kidney transplantation. The objective was to develop clinical practice recommendation (CPR) focusing on the specific aspects of the kidney management of this disease.Development of these CPRs is an initiative of the European Reference Network (ERN) for Rare Kidney Diseases (ERKNet) in collaboration with the ERN for Hereditary Metabolic Disorders (MetabERN) and included pediatric and adult nephrologists, metabolic specialists, liver, and kidney transplant specialists.CKD has become a significant clinical issue that requires a specific follow up in both pediatric and adults’ departments. Creatinine-based formulae significantly overestimate kidney function and the estimation of eGFR is more accurate using cystatin C. Besides usual kidney indications, acute dialysis may be required in emergency in case of acute metabolic decompensation to clear metabolic toxins. Long-term dialysis may be initiated for clearance of toxic metabolites. Long hours on hemodialysis and/or frequent daily dialysis are required. The indications for transplantation in MMA are a high rate of metabolic decompensations, a high burden of disease and difficult metabolic control. Transplantation is also indicated in case of long-term complications. Combined liver-kidney transplantation should be preferred in MMA patients with chronic kidney disease. Possible calcineurin inhibitors induced neurotoxicity was described in MMA patients requiring immunosuppressive treatment monitoring and adaptation.Overall, 13 statements were produced to provide guidance on management of CKD, dialysis and transplantation in MMA pediatric and adult patients.