From the Guidelines
Tolvaptan is a recommended treatment for adults with rapidly progressing Autosomal Dominant Polycystic Kidney Disease (ADPKD), as it slows kidney function decline and cyst growth, with a typical dosing starting at 45 mg in the morning and 15 mg 8 hours later, as supported by the KDIGO 2025 clinical practice guideline 1. The evidence from the KDIGO 2025 guideline suggests that tolvaptan is effective in reducing the rate of kidney function decline and cyst growth in ADPKD patients, with a net difference in eGFR decline of 1.3 ml/min per 1.73 m2 per year and in total kidney volume growth of 2.7% favoring tolvaptan use 1. Some key points to consider when prescribing tolvaptan include:
- Initiating treatment with a daily dose of 45 mg upon waking, and 15 mg 8 hours later, with potential titration to 60/30 mg and 90/30 mg based on tolerability 1
- Monitoring liver function tests monthly for the first 18 months, then every 3 months thereafter, due to the risk of liver injury 1
- Advising patients to drink adequate water (2-3 liters daily) to prevent dehydration due to the aquaretic effect of tolvaptan 1
- Discontinuing treatment if liver injury occurs or if the patient reaches end-stage kidney disease requiring dialysis or transplantation 1 Overall, the use of tolvaptan in ADPKD patients has been shown to be effective in slowing disease progression, and its benefits outweigh the risks, making it a recommended treatment option for adults with rapidly progressing ADPKD 1.
From the FDA Drug Label
In placebo-controlled studies and an open-label extension study of chronically administered tolvaptan in patients with ADPKD, cases of serious liver injury attributed to tolvaptan, generally occurring during the first 18 months of therapy, were observed Tolvaptan should not be used to treat ADPKD outside of the FDA-approved risk evaluation and mitigation strategy (REMS) for ADPKD patients [see Contraindications ( 4)] Because of the risk of hepatotoxicity, tolvaptan should not be used for ADPKD outside of the FDA-approved REMS [see Contraindications ( 4)]
The role of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease (ADPKD) is to slow the rate of kidney function decline in certain patients, but it should only be used within the FDA-approved risk evaluation and mitigation strategy (REMS) due to the risk of liver injury. Key points to consider are:
- Liver injury risk: Tolvaptan can cause serious and potentially fatal liver injury, especially in the first 18 months of therapy.
- REMS requirement: Tolvaptan should not be used to treat ADPKD outside of the FDA-approved REMS.
- Contraindications: Tolvaptan is contraindicated in patients with ADPKD outside of the FDA-approved REMS 2, 2, 2.
From the Research
Role of Tolvaptan in ADPKD
Tolvaptan, a vasopressin V2 receptor antagonist, plays a significant role in the treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD). The key aspects of its role are:
- Slowing down renal function decline in ADPKD patients 3, 4, 5, 6, 7
- Reducing the growth of total kidney volume 4, 7
- Delaying the progression of ADPKD in adults with stage 1-3 chronic kidney disease 4
- Associated with a lower rate of events for the composite secondary endpoint of time to investigator-assessed clinical progression 4, 7
Patient Selection and Special Considerations
The selection of patients for tolvaptan treatment is crucial and complex. Key considerations include:
- Identifying patients with high risk of rapid progression 3, 6
- Using different assessment strategies for tolvaptan eligibility 3
- Balancing benefits and risks, including adverse events such as polyuria, nocturia, polydipsia, and thirst 4, 6, 7
- Monitoring for idiosyncratic hepatotoxicity, which is reversible on discontinuation of the drug 4, 7
Efficacy in Different Patient Populations
Tolvaptan has been shown to be effective in various patient populations, including: