On April 24, 2018, the U.S. Food and Drug Administration (FDA) approved the drug tolvaptan as the first treatment available in the U.S. for adults with autosomal dominant polycystic kidney disease (ADPKD), the most common form of polycystic kidney disease (PKD). While further research is needed, here’s what we know about the benefits and risks of tolvaptan for treating ADPKD.*

What is tolvaptan, and how does it help?

The approval of tolvaptan was based on the results of:

• The TEMPO trial, which strongly indicated that tolvaptan could slow kidney cyst growth and preserve kidney function
• The REPRISE trial, which confirmed the results of the TEMPO trial by demonstrating the drug’s ability to slow the progression of chronic kidney disease stages 3 and 4 over 12 months 

The studies collectively suggested that tolvaptan can slow kidney function loss by 20% to 30%—potentially extending kidney function by many years and delaying the need for dialysis and/or kidney transplantation. Not all patients can tolerate tolvaptan, however; between 10% and 16% of study participants withdrew from therapy before the trials ended.

Tolvaptan is taken twice daily as an oral pill and influences how the kidneys control the concentration of urine. It has been shown to slow down the growth of kidney cysts when it is taken for several years by adults at risk of swiftly-progressing ADPKD. Tolvaptan’s kidney function benefits are similar to those of the renin-angiotensin-aldosterone system (RAAS) inhibitors used for diabetic nephropathy.

What are tolvaptan’s side effects?

The major known side effects of tolvaptan include:

• Thirst
• Frequent urination
• Increased urine volume
• Nighttime urination
• Potentially serious liver injury, though this is rare 

Patients taking tolvaptan must remain under the care of the prescribing physician, so that side effects can be properly monitored. The drug should be discontinued at the first sign of elevated liver enzymes in a blood test. This is usually reversible if the drug is stopped in a timely fashion.

Further research

Attempts are being made to identify those patients most likely to benefit from tolvaptan. The FDA approval currently limits the target population to those considered to be at high risk for disease progression. 

Risk factors for rapid disease progression include:

• A significantly larger total kidney volume than expected for their age 
• Family history of kidney failure before the age of 58
• High blood pressure (hypertension) before the age of 35 
• Bleeding, pain, and other urologic symptoms before the age of 35  
• A decline in eGFR of ≥5 mL/min within a year
• Specified genetic profiles
• Being of the male sex

Research and development costs for drugs and treatment devices are high and continue to rise. Many diseases, including kidney disease, carry growing management costs, as well. To identify options and improve outcomes, while ensuring that healthcare dollars are getting the most effective, highest-value use of tolvaptan in PKD, further studies must:

• Delineate the long-term benefits and risks
• Study early-disease and very-late disease populations (to preserve GFR in advanced stages and residual function on dialysis)

Additional information on tolvaptan can be found on the Kidney News Online and Oxford University Hospitals (U.K.) websites.

*PKD Foundation. (2020, Nov.  2). Tolvaptan treatment for ADPKD. https://pkdcure.org/tolvaptan/