Abstract: SA-PO765
Tolvaptan Use in Patients with Autosomal Dominant Polycystic Kidney Disease and Gilbert Syndrome
Session Information
- Genetic Diseases: Cystic - Genetic Analysis and Extrarenal Manifestations
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Cystic
Author
- Marn Pernat, Andreja, University Medical Center Ljubljana, Ljubljana, Slovenia
Introduction
Jinarc therapy is contraindicated in patients with elevated liver enzymes. Gilbert's syndrome, one of the most common genetic disorder, is characterised by mild fluctuating unconjugated hyperbilirubinemia. A search of the available medical literature did not identify any studies or information that evaluated the use of tolvaptan in patients with ADPKD and Gilbert's syndrome. We present two cases with ADPKD and Gilbert's syndrome, in whom treatment with tolvaptan was initiated.
Case Description
Case 1 was a 31- year-old male patient and Case 2 was a 34-year-old female sibling. They have rapidly progressive ADPKD and a family history of Gilbert's syndrome. Blood testing for systemic markers of liver function were performed prior to and two weeks after initiation of Jinarc, continuing monthly thereafter. Their renal function was normal. Both patients received Jinarc 45 mg in the morning and 15 mg in the afternoon, and the dose was not increased during first 4 months of follow-up. A sustained urine osmolality (Uosm) of 280 mOsm/kg was achived in both patients. Case 1 had Uosm between 65 nad 138 mOsm/kg and Case 2 between 43 and 287 mOsm/kg. Case 1 had mild hyperbilirubinemia prior to tolvaptan initiation but no significant additional elevation of bilirubin was observed during treatment. Case 2 had an increase in bilirubin immediately after starting treatment but it remained < 2 ULN thereafter. The table presents the bilirubin values in both patients before and during tolvaptan therapy. All other parameters of potential hepatocellular injury, including hepatic transaminases, were within the normal range in the first 4 months.
Discussion
In two young adult siblings with rapidly progressive ADPKD and a benign Gilbert's syndrome we cautiously started treatment with tolvaptan. We observed an isolated elevated serum bilirubin in the absence of the other criteria for hepatic injury. We feel that patients with Gilbert's syndrome can also be considered for tolvaptan therapy. Still, safety studies in patients with impaired bilirubin glucuronidation are warranted.
Total and direct bilirubin presented for cases 1 and 2.
| Prior tolvaptan | After 2 weeks | 1 month | 2 months | 3 months | 4 months | |
| Total bilirubin, mcgmol/L Case 1 Case 2 | 37 19 | 35 28 | 24 30 | 25 22 | 28 31 | 30 31 |
| Direct bilirubin,mcgmol/L Case 1 Case 2 | 10 5 | 13 10 | 10 11 | 10 8 | 11 11 | 11 12 |