PII-026 - BILE ACIDS AS POTENTIAL BIOMARKERS TO ASSESS LIVER IMPAIRMENT IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD).
Thursday, March 23, 2023
5:00 PM – 6:30 PM EDT
J. Tiley1, V. Fomin2, L. Wang3, W. Jia4, H. Jiang2, S. Roth2, K. Brouwer1; 1University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 2Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, MD, USA, 3Hong Kong Baptist University,, Kowloon, Hong Kong SAR,, China, 4Hong Kong Baptist University, Kowloon, Hong Kong SAR, China.
Assistant Professor University of North Carolina at Chapel Hill Graham, North Carolina, United States
Background: ADPKD is a genetic disorder that causes the development of renal cysts and utlimately leads to end stage kidney disease. Tolvaptan (TOL) slows the disease progression in patients with ADPKD and also has potential to cause hepatotoxicity in a fraction of patients. TOL and its metabolites inhibit various hepatic transporters, which may cause elevated liver enzymes [e.g., alanine aminotransferase (ALT)]. Bile acids (BAs), known endogenous substrates for some hepatic transporters, may facilitate identification of patients with ADPKD who are more susceptible to hepatotoxicity due to impaired hepatic transporter function. The goal of this study was to compare changes in the plasma BA profiles in TOL-treated patients with and without ALT elevations. Methods: Three plasma samples (Timepoint 1: baseline, 2: on treatment, 3: at ALT elevation or 7-9 months after baseline sample for the control) collected from TOL-treated patients who were enrolled in the REPRISE trial (NCT02160145) with (case, n=22) and without (control, n=22) ALT elevations were analyzed. Plasma BAs were quantified by ultra-performance liquid chromatography coupled to tandem mass spectrometry. Results: BA profiling revealed significant changes for specific BAs and BA species (p < 0.05; shown are adjusted p-values): 1) Glycohyocholate (0.018) at Timepoint 3 between case and control; 2) Taurohyocholate (0.011), Taurocholate (0.011) and taurine conjugated BAs (0.004) comparing Timepoint 1 vs. 3 within cases; 3) Taurocholate (0.034), Glycocholate (0.045) and taurine conjugated BAs (0.019) comparing Timepoint 2 vs 3 within cases. Conclusion: Based on these data, measurement of some plasma BAs over time may be useful in TOL-treated patients with ADPKD to determine susceptibility to adverse liver events.
