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Review
. 2025 Apr;40(4):891-899.
doi: 10.1007/s00467-024-06562-8. Epub 2024 Oct 24.

Kidney and vascular involvement in Alagille syndrome

Bruno Ranchin  1 , Marie-Noelle Meaux  2   3 , Malo Freppel  2   3 , Mathias Ruiz  4 , Aurelie De Mul  2   3   5
Affiliations
Review

Kidney and vascular involvement in Alagille syndrome

Bruno Ranchin et al. Pediatr Nephrol. 2025 Apr.

Abstract

Alagille syndrome (ALGS) is an autosomal dominant, multisystemic disease with a high interindividual variability. The two causative genes JAG1 and NOTCH2 are expressed during kidney development, can be reactivated during adulthood kidney disease, and Notch signalling is essential for vascular morphogenesis and remodelling in mice. Liver disease is the most frequent and severe involvement; neonatal cholestasis occurs in 85% of cases, pruritus in 74%, xanthomas in 24% of cases, and the cumulative incidences of portal hypertension and liver transplantation are 66% and 50% respectively at 18 years of age. Stenosis/hypoplasia of the branch pulmonary arteries is the most frequent vascular abnormality reported in ALGS. Kidney involvement is present in 38% of patients, and can reveal the disease. Congenital anomalies of the kidney and urinary tract is reported in 22% of patients, hyperchloremic acidosis in 9%, and glomerulopathy and/or proteinuria in 6%. A decreased glomerular filtration rate is reported in 10% of patients and is more frequent after liver transplantation for ALGS than for biliary atresia. Kidney failure has been frequently reported in childhood and adulthood. Renal artery stenosis and mid aortic syndrome have also frequently been reported, often associated with hypertension and stenosis and/or aneurysm of other large arteries. ALGS patients require kidney assessment at diagnosis, long-term monitoring of kidney function and early detection of vascular complications, notably if they have undergone liver transplantation, to prevent progression of chronic kidney disease and vascular complications, which account for 15% of deaths at a median age of 2.2 years in the most recent series.

Keywords: Alagille syndrome; Congenital anomalies of the kidney and urinary tract; Kidney; Renal artery stenosis; Vascular.

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Conflict of interest statement

Declarations. Conflicts of interest: The authors have no conflicts of interest to declare.

Figures

None
A higher resolution version of the Graphical abstract is available as Supplementary information
Fig. 1
Fig. 1
Clinical features of Alagille syndrome. Written consent for publication of these images was obtained from the patients and their parents
See this image and copyright information in PMC

References

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