From the Guidelines
Tolvaptan, a Vasopressin V2 receptor antagonist, has been shown to delay disease progression in adults with Autosomal Dominant Polycystic Kidney Disease (ADPKD) 1.
Effects on ADPKD Progression
- In adults, Tolvaptan has been licensed to delay disease progression in those likely to develop End-Stage Renal Disease (ESRD) 1.
- It has also been shown to reduce ADPKD-related pain 1.
Use in Children and Adolescents
- Currently, there is no direct data to support the use of Tolvaptan in children and adolescents with ADPKD 1.
- A multinational, double-blind, placebo-controlled trial of Tolvaptan in teenagers with ADPKD is currently underway 1.
- The use of Tolvaptan in children and young people with ADPKD is not routinely recommended, but may be considered off-label in those at high risk of early progression 2.
Important Considerations
- Tolvaptan can cause occasional hepatic injury in adult ADPKD patients 1, and its impact on liver enzymes in children is not yet known.
- Treatment with Tolvaptan can also cause substantial polyuria, affecting sleep and daily activities, and potentially influencing quality of life 1.
From the FDA Drug Label
TOLVAPTAN tablets, for oral use ... (B) NOT FOR USE FOR AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD) ... CONTRAINDICATIONS • Use in patients with autosomal dominant polycystic kidney disease (ADPKD) outside of FDA-approved REMS ( 4)
The FDA drug label does not provide information on how Tolvaptan affects the progression of Autosomal Dominant Polycystic Kidney Disease (ADPKD), it only states that it is not for use in patients with ADPKD outside of the FDA-approved REMS due to the risk of hepatotoxicity 3.
From the Research
Effects of Tolvaptan on ADPKD Progression
- Tolvaptan, a selective vasopressin V2 receptor antagonist, has been shown to delay the progression of Autosomal Dominant Polycystic Kidney Disease (ADPKD) by suppressing increases in kidney volume and renal injury 4, 5.
- The TEMPO 3:4 trial demonstrated that tolvaptan significantly reduced the growth in total kidney volume and slowed renal function decline in patients with ADPKD 5, 6.
- Tolvaptan has also been shown to reduce kidney pain and the risk of worsening renal function in patients with ADPKD 5, 6.
Mechanism of Action
- Tolvaptan's mechanism of action involves the inhibition of V2-driven adenosine cyclic 3',5'-monophosphate generation, leading to aquaretic, hemodynamic, and anti-secretory actions 7.
- The drug has been shown to induce aquaresis, reduce glomerular filtration rate, and increase serum uric acid levels in patients with ADPKD 7.
Determinants of Response to Tolvaptan
- Baseline urine osmolality, eGFR, and total kidney volume have been identified as factors that influence the response to tolvaptan in patients with ADPKD 8.
- The greatest renal benefit from tolvaptan has been observed in subjects with better eGFR at baseline and those who achieve greater suppression of urine osmolality 8.
Adverse Effects
- Tolvaptan has been associated with aquaretic effects, such as polyuria, nocturia, and polydipsia, as well as elevations in liver enzymes and the potential for acute liver failure 5, 6.
- Appropriate patient selection and monitoring are critical to minimize the risks associated with tolvaptan treatment 6.