In 2015 families in Wales and England were given the good news that tolvaptan (JINARC®), which was developed for autosomal dominant polycystic kidney disease (ADPKD), will be available within one year.
According to a recent article in the Nephrology Times, Dr. Judith Munoz and her associates in Spain conducted a two-year follow-up to the TEMPO trial. The team is studying tolvaptan in terms of safety and effectiveness as a follow-up to the trial during the initial two years of treatment.
The first drug to treat ADPKD
Tolvaptan (JINARC®) is the first of its kind to treat what researchers term as one of the world’s most widespread kidney diseases. ADPKD is the fourth leading cause of end-stage renal disease in adults.
Although the disease was first identified in the sixteenth century, at this moment there is still no cure.
Tolvaptan has been recommended for treatment in adults who have ADPKD and chronic disease of the kidneys at stage two or three. There must also be evidence that their disease is rapidly progressing. The disorder affects males, females, and all ethnic groups equally across the globe.
Tolvaptan functions by inhibiting an ‘antidiuretic hormone’ called vasopressin which regulates sodium and water in kidneys. Vasopressin is primarily responsible for the formation of kidney cysts, fluid secretion, and their growth. Vasopressin is also responsible for the significant enlargement of polycystic kidneys.
Tolvaptan is a selective vasopressin V2 receptor (blocker) that binds to a receptor instead of activating it. Tolvaptan is a new generation diuretic.
ADPKD: A Complex Disease
The most notable characteristic of ADPKD is the existence of cysts or filtering units in the kidney that are filled with fluid. The one million or more filtering agents are called nephrons.
It is well known that the kidney is an essential filtering agent that is responsible for the daily filtering of blood. But in time, with ADPKD, the cysts will become larger in weight, volume, and size and will interfere with healthy tissue.
An ADPKD kidney can grow over fifty times larger than a normal size kidney. Cysts can become as large as the kidney itself, become painful, cause infections, and/or burst. It may be necessary to aspirate the cyst or possibly remove one or both kidneys.
Some patients will advance to end-stage renal disease (ESRD) before the age of sixty. If ESRD does occur, dialysis or transplantation can often save the patient’s life.
About the 2015 TEMPO Trial
TEMPO, a three-year clinical trial, was the largest study of ADPKD conducted at the time.
Compared to the placebo arm, tolvaptan reduced abnormal kidney enlargement by about fifty percent. Importantly, patients saw a decrease in the loss of kidney function. The drug also reduced infections and pain.
Otsuka Pharmaceutical Ltd provided funding for development and clinical trials of tolvaptan.
About the TEMPO Follow-up
One hundred forty-three ADPKD patients who had kidney disease (stage one to four) received tolvaptan. Data from fifteen centers in Madrid, Spain were collected.
The median follow-up was eight months. Seventy-four percent of patients had adverse events. Sixty-eight percent of these patients exhibited an exceptionally heavy volume of urine plus frequency of urination (polyuria) during the day and at night.
At about eleven months, thirty-one patients discontinued treatment. Although fourteen patients reported high liver enzyme levels, there were no reports of severe liver injury.
The major reason for discontinuance was from the drug which, as reported previously, caused a heavy volume of urine plus frequency of urination. However, nine of the thirty-one patients returned to the trial and continued treatment.
In summary, the authors of the TEMPO trial considered tolvaptan as a drug that is safe for ADPKD patients to take. Data that was obtained from a subsequent trial, REPRISE, was similar in nature.
The doctors point out that due to various adverse events, the enzyme levels in the liver should be monitored. They emphasized that there had been no liver damage fatalities reported and that after being treated for two years, the patients’ renal functions were stable.