Ultrasound evaluation of kidney and liver involvement in Bardet-Biedl syndrome

Abstract

Background Bardet-Biedl syndrome (BBS) is a rare autosomal-recessive ciliopathy with pathogenic variants in at least 26 BBS genes. It affects multiple organs including kidney and liver, however, organ involvement differs widely regarding extent and time of first manifestation. Structural renal anomalies are an early feature with a frequency of > 50% and end-stage kidney disease (ESKD) cumulates to 25% in adolescence. Early-onset hyperphagia-associated obesity is another major symptom and contributes to liver pathology, presenting as steatosis/fibrosis. Aim of this study is the evaluation of high-end ultrasound (US) technologies including shear wave elastography (SWE), dispersion (SWD), and attenuation imaging (ATI) in BBS patients regarding their potential to discriminate liver and kidney tissue pathology at an early stage. Materials and Methods Patients with genetically proven BBS were recruited from the University Children’s Hospital of Essen and from BBS patient days hosted in Germany. Acute illness was an exclusion criterion. Clinical and laboratory data were extracted from patients’ digital records or medical letters. Results 49 BBS patients (24/49 male; aged 1.1–51.0 years, mean 17.8 years) were included in the study. Mean body weight (SDS 2.13 ± 1.33) and BMI (SDS 2.64 ± 1.18) were increased. Structural kidney abnormalities (dysplasia, cysts) were present in 75% (36/48) and persistent fetal lobulation in 44% (21/48). Renal function was impaired in 27% (13/49) and 3/13 had ESKD (kidney transplantation (n = 2), hemodialysis (n = 1)). Elevation of liver enzymes was detected in 38% (16/42). In 51% (25/49) ATI of liver tissue was increased, indicating hepatic steatosis, and correlated with BMI SDS, liver size, and enzymes. SWE was elevated in 61% (30/49) suggesting hepatic fibrosis and was associated with BMI and GGT. Patients with pathogenic variants in BBS10 showed a tendency towards higher ATI and reduced GFR, and had significantly higher BMI SDS. Conclusions We detected abnormalities of the kidney and liver in a higher percentage of BBS patients than previously reported, indicating a high sensitivity of the evaluated US applications. ATI detected liver pathology early (partially prior to liver enzymes) and revealed differences related to the affected genes. Evidence of tissue pathology at an early stage may improve diagnostics and the evaluation of therapeutic approaches.