ABCB4 variants in adult patients with cholestatic disease are frequent and underdiagnosed.

BACKGROUND: Heterozygous ABCB4 variants are not routinely tested in adults with cholestasis because of their supposed rarity and high costs. METHODS: Nineteen adult patients presenting with unexplained cholestasis, and/or recurrent gallstones were included; genotyping was not done in five due to lack of health insurance approval. RESULTS: heterozygous ABCB4 variants were identified in seven patients, followed by cascade testing of 12 family members: one patient underwent liver transplantation at age 40 for end-stage liver disease; one had compensated cirrhosis; all symptomatic adults had gallstones, including four with low phospholipid-associated cholelithiasis; four had intrahepatic cholestasis of pregnancy; all children and one 54-year old female were asymptomatic. Genotype: Families A and C: c.2211G>A (p.Ala737=) combined with c.959C>T (p.Ser320Phe) in one subject; Family B: c.1130T>C (p.Ile377Thr); Family D: large deletion removing ABCB4 exons 1-4 plus ABCB1, RUNDC3B, SLC25A40, DBF4, ADAM22 exons 1-3; Family E: c.1565T>C (p.Phe522Ser) ; Family F: c.1356+2T>C combined with c.217C>G (p.Leu73Val). All patients responded to ursodeoxycholic acid. CONCLUSIONS: We found ABCB4 variants in half of the adults with unexplained cholestasis and/or recurrent gallstones presenting at our center, suggesting that this condition is underdiagnosed and undertreated, with serious consequences not only for the patients and their families, but also in terms of healthcare costs.

Impaired Daytime Urinary Sodium Excretion Impacts Nighttime Blood Pressure and Nocturnal Dipping at Older Ages in the General Population.

The circadian rhythm of urinary sodium excretion is related to the diurnal blood pressure regulation (BP) and the nocturnal dipping pattern. The renal sodium excretion expressed as daytime/nighttime ratio impacts BP, but a limited number of studies have investigated this topic to date. In this cross-sectional study, we aimed to investigate the impact of different daily patterns of sodium excretion (comparing low with high ratios) on BP and nocturnal dipping and to explore the relationship with age. Twenty-four-hour ambulatory BP monitoring and daytime and nighttime urinary sodium collections were used to assess 1062 subjects in Switzerland. Analyses were performed according to the day/night urinary sodium excretion ratio quartiles (Q1-Q4) and by age group (≤50 and ≥50 years). Subjects in Q1 can be considered low excretors of sodium during the daytime since the rate of sodium excretion during the daytime was 40% lower than that of subjects in Q4. Quartiles of the day/night urinary sodium excretion ratio showed that subjects in Q1 were 7 years older and had respectively 6 and 5 mmHg higher nighttime systolic and diastolic BP and a higher nocturnal dipping compared with subjects in Q4 (p-value ≤0.001). Associations found were significant only for subjects older than 50 years (all p < 0.05). The present results suggest that a decreased capacity to excrete sodium during daytime is more prevalent as age increases and that it impacts nighttime blood pressure and nocturnal dipping in older subjects.