Chronic kidney disease in Bardet-Biedl syndrome: evidence supporting multifactorial etiology

IntroductionChronic kidney disease (CKD) is a critical prognostic factor in Bardet-Biedl syndrome (BBS). Early diagnosis and intervention are essential for improving patients' outcomes. The present study has analyzed kidney function in BBS patients, with the aim to explore the impact of genetic variants and common risk factors for kidney diseases.MethodsA monocentric cross-sectional study has been conducted. Patients underwent genetic analysis via Next Generation Sequencing; renal function has been assessed and the relationship with (I) age, obesity and hypertension and with (II) genetic mutations has been analyzed.ResultsA total of 65 BBS patients were enrolled in the study; renal function was variable, with 25% of patients showing an estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73m2. Patients' age was inversely correlated with the eGFR (p=0.002). Reduced eGFR significantly correlated with truncating mutations in any BBS gene and hypertension; moreover, multivariate analysis using eGFR as an objective variable and multiple risk factors as explanatory variables, showed that body mass index (BMI) was independently associated with eGFR decline (β=-2.45, p<0.0001), in addition to age. Interestingly, significant discordance in renal phenotype was revealed in 50% of subgroups of consanguineous or non-consanguineous patients sharing the same pathogenic variants, indicating clinical variability even in this setting.ConclusionThe present study suggests that BBS is a condition of vulnerability to develop kidney disease and that age, hypertension and obesity are associated with eGFR decline in adult BBS patients; whether effective interventions to treat modifiable factors will reduce CKD risk requires further studies.