S LEE1, M THOMAS2, R BAKER3
1University of WA, Perth, Australia, 2Royal Perth Hospital, Perth, Australia, 3Royal Perth Hospital, Perth, Australia
Background: Tolvaptan (TVT) is a vasopressin V2 receptor antagonist which reduces the rate of cyst growth and CKD progression in patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD). In the TVT REPRISE trial, 5.6% of TVT subjects had raised liver function tests (LFTs) vs 1.2% of placebo subjects, which reversed on TVT withdrawal, suggesting direct TVT hepatotoxicity. However, hepatotoxicity was not detected in hyponatraemic TVT trials (eg CCF and SIADH) where fluid intake is restricted rather than encouraged. Hepatotoxicity may be exacerbated by medications, concurrent liver disease and intake of carbonated artificially sweetened beverages (CASB).
Case report: A 56 year-old man with obesity and ADPKD received TVT since 2008, other than 6 months planned TVT withdrawal in 2011-2012. To alleviate TVT induced thirst, he increased CASB intake from 0.7L to 1.5L daily, followed over a year by doubling in alanine aminotransferase (ALT) and 12kg increase in weight to 114kg (BMI 35). During TVT withdrawal in 2011 to 2012, he reduced CASB intake whilst less thirsty and ALT fell back to baseline pre-TVT, and rose again after TVT recommencement. He then switched from CASB to water in late 2012 with normalisation of ALT ever since 2013, despite only modest weight loss and continued TVT. During his trial on TVT, he had minimal alcohol intake, no change in liver cysts or concurrent liver infections, and no significant increase in ALT after commencing a statin.
Conclusions: We believe hepatotoxicity in patients on tolvaptan may be due to their choice of fluid intake (and specifically carbonated artificially sweetened beverages) taken to relieve hypernatraemic thirst, rather than the drug itself. Medication safety needs to include lifestyle advice.
Nephrologist at RPH since 1988, principal investigator in tolvaptan trials since 2008