Liver transplantation does not impact the renal function outcome in Alagille syndrome

Abstract

Background and Aims: Alagille syndrome (AS) is an autosomal dominant multi-systemic disorder caused by pathogenic variants in JAG1 and NOTCH2. Characteristic findings include hepatic involvement with bile duct paucity and 20-50% eventually need a liver transplantation. Post-LT Tacrolimus induced nephropathy is well recognised and 40% of AS patients have an underlying renal anomaly. In the current study we analysed the impact of LT and Tacrolimus on the evolution of renal function (RF) in children with AS. Methods: Retrospective study including 50 children that satisfied 3 of 5 major Alagille syndrome criteria and under regular follow-up at our centre between 1984 and 2016. Clinical, biochemical and radiological data were collected at similar time points of follow-up among the transplanted and non-transplanted children. The time points were at diagnosis or at LT and after 1-2 years, 2-3 years, 3-5 years, 5-7 years and 7-10 years of follow-up. The RF was estimated by glomerular filtration rate (eGFR) using the updated Schwartz formula. The RF outcomes of children with AS having undergone LT were compared with those without LT and also with children having undergone LT for non-AS related indication but without associated nephropathy. Results: 28 of 50 (56%) included AS children underwent LT and were compared with 77 children transplanted for non-AS indications. Mean eGFR post-LT in AS patients and non-AS patients were 93.8 mL/min and 143.2 mL/min, respectively (difference: 49.4 mL/min, p<0.0001). Among children with AS mean eGFR observed in those who did not receive LT was 87.9 mL/min, -5.9 mL/min compared to those who received LT though this was statistically insignificant (p=0.32). Presence of renal ultrasound abnormalities was correlated to RF impairment in AS patients, with or without LT: -14.6 mL/min (98.5 mL/min vs 83.9 mL/min, p=0.03) and -40.9 mL/min (97.8 mL/min vs 56.9 mL/min, p<0.0001), respectively. Conclusions: Post-LT renal function outcomes are significantly worse in children with AS being the primary disease. Among the children with AS, the RF outcome is not worse after LT