Long-term outcome after combined or sequential liver and kidney transplantation in children with infantile and juvenile primary hyperoxaluria type 1

Abstract

IntroductionCombined or sequential liver and kidney transplantation (CLKT/SLKT) restores kidney function and corrects the underlying metabolic defect in children with end-stage kidney disease in primary hyperoxaluria type 1 (PH1). However, data on long-term outcome, especially in children with infantile PH1, are rare.MethodsAll pediatric PH1-patients who underwent CLKT/SLKT at our center were analyzed retrospectively.ResultsEighteen patients (infantile PH1 n = 10, juvenile PH1 n = 8) underwent transplantation (CLKT n = 17, SLKT n = 1) at a median age of 5.4 years (1.5–11.8). Patient survival was 94% after a median follow-up of 9.2 years (6.4–11.0). Liver and kidney survival-rates after 1, 10, and 15 years were 90%, 85%, 85%, and 90%, 75%, 75%, respectively. Age at transplantation was significantly lower in infantile than juvenile PH1 (1.6 years (1.4–2.4) vs. 12.8 years (8.4–14.1), P = 0.003). Median follow-up was 11.0 years (6.8–11.6) in patients with infantile PH1 vs. 6.9 years (5.7–9.9) in juvenile PH1 (P = 0.15). At latest follow-up kidney and/or liver graft loss and/or death showed a tendency to a higher rate in patients with infantile vs. juvenile PH1 (3/10 vs. 1/8, P = 0.59).DiscussionIn conclusion, the overall patient survival and long-term transplant outcome of patients after CLKT/SLKT for PH1 is encouraging. However, results in infantile PH1 tended to be less optimal than in patients with juvenile PH1.

Primary hyperoxaluria: Description of a new oral finding and review of literature

“…Treatment options in hyperoxaluria include hydration, citrate supplementation, vitamin B6, renal dialysis, kidney transplant, and combined or sequential liver and kidney transplant. 27 Recently, Lumasiran, an RNA interference (RNAi) compound that block endogenous oxalate production and lower plasma/urine oxalate, has been approved by the U.S Food and Drug Administration (FDA) for treatment of PH-type 1. 28 Management of root resorption and tooth mobility in hyperoxaluria is poorly described in the literature, and clinical recommendations are lacking.…”

Review of childhood genetic nephrolithiasis and nephrocalcinosis

“…Treatments of PH1 that have been tested include substrate reduction therapy to target enzymes responsible for production of oxalate with RNA interference (RNAi) (targeting glycolate oxidase [GO] with Lumasiran, LDH with Nedosiran) and CRISPR (targeting GO, LDH) ( Zabaleta et al, 2018 ; Martinez-Turrillas et al, 2022 ; Sas et al, 2022 ; Baum et al, 2023 ; Hayes et al, 2023 ), small molecules to prevent AGT mistargeting ( Miyata et al, 2014 ), enhanced intestinal oxalate degradation using probiotics (Oxalobacter formigenes) or enzymes (oxalate decarboxylase) ( Milliner et al, 2018 ; Lingeman et al, 2019 ; Quintero et al, 2020 ), and restoration of functional enzyme conformation with chaperone therapy (vitamin B6) ( Fargue et al, 2013 ). Definitive treatment involves combined or sequential liver and kidney transplant ( Loos et al, 2023 ).…”

Navigating the Evolving Landscape of Primary Hyperoxaluria: Traditional Management Defied by the Rise of Novel Molecular Drugs

“…There is an ongoing debate about the comparative merits of CLKT and sequential liver-kidney transplantation (SLKT) for PH patients, with three high-quality studies revealing no significant differences in the overall survival and renal transplant survival rates between the two approaches [99][100][101]. A 2023 study on long-term outcomes for infants and adolescents with PH1 (n = 18) undergoing CLKT/SLKT showed encouraging results, with a 94% patient survival rate (median followup of 9.2 years) and liver and kidney transplant survival rates reaching 85% and 75%, respectively, after 15 years [102]. However, pre-emptive liver transplantation (PLT) as a transplant strategy remains controversial.…”