Tolvaptan Use in Autosomal Dominant Polycystic Kidney Disease

Indications and Efficacy

Tolvaptan is a vasopressin V2-receptor antagonist that slows ADPKD progression by reducing the rate of eGFR decline by approximately 1.3 ml/min/1.73 m² per year and decreasing total kidney volume growth by 2.7% compared to placebo 1, 2
The American College of Cardiology recommends tolvaptan for patients with ADPKD at risk of rapid disease progression, with careful monitoring for hepatotoxicity and management of aquaresis 1, 2

Initial dosing should be 45 mg upon waking and 15 mg 8 hours later, with gradual titration to a target dose of 90 mg in the morning and 30 mg in the afternoon 1, 2
Dosing should be adjusted based on tolerability and response, with consideration for downtitration in cases of concurrent CYP3A inhibitor use, intolerance or side effects, and elevated liver enzymes 2

Liver function tests must be monitored monthly for the first 18 months, then every 3 months until drug discontinuation, and serum sodium levels should be monitored to assess adequacy of water intake 2, 3
Tolvaptan should be permanently discontinued if ALT or AST increase to ≥3× upper limit of normal (ULN) and do not improve, or if the patient shows signs and symptoms of liver injury 2

Aquaresis-related effects (polyuria, thirst, dry mouth) are common and require adequate fluid intake, and patients should be counseled to drink adequate amounts of water, consume liquids without sugar or fat, and adopt a low-sodium diet to reduce polyuria 1, 2

Tolvaptan treatment should be continued until approaching kidney replacement therapy if well-tolerated, and can be continued in patients aged >55 years and/or when eGFR falls below 25 ml/min/1.73 m² if well tolerated 1, 2
Strong and moderate CYP3A inhibitors should be avoided, including antifungals, antibiotics, protease inhibitors, and grapefruit juice 2, 3

Tolvaptan is not routinely recommended for children and young people with ADPKD, but off-label use can be considered at clinician discretion in children at high risk of early progression based on large total kidney volume, rapid kidney growth, and family history 4, 5

Mandatory discontinuation is required if liver enzymes increase to ≥3× upper limit of normal or if the patient shows signs and symptoms of liver injury, as recommended by the Kidney International guidelines 6

After discontinuing tolvaptan, patients should increase water intake to 2-3 liters per day to help maintain kidney function, according to the Kidney International guidelines 6
Regular monitoring of kidney function and total kidney volume should continue to assess disease progression, as suggested by the Kidney International guidelines 6
Patients should be counseled about the importance of other protective measures, including a low-salt diet, regular physical exercise, avoiding obesity and smoking, and avoiding nephrotoxic medications, as recommended by the Nature Reviews Nephrology guidelines 7

For patients with liver injury who discontinue tolvaptan, all abnormalities should be followed until they return to normal or baseline state, according to the Kidney International guidelines 6
If tolvaptan was discontinued due to side effects rather than liver injury, and the benefits outweigh the risks, rechallenge can be considered with more frequent monitoring, as suggested by the Kidney International guidelines 6

Provide reassurance that alternative management strategies can still help manage symptoms and slow progression, according to the Kidney International guidelines 6
Address any psychological concerns related to disease progression, as these can significantly impact well-being, as recommended by the Nature Reviews Nephrology guidelines 7
Emphasize the importance of continued monitoring and adherence to other protective measures, such as lifestyle modifications, as recommended by the Nature Reviews Nephrology guidelines 7