Tolvaptan, an oral vasopressin receptor 2
antagonist has slowed
the rate of decline in kidney function in patients with autosomal dominant polycystic kidney damage (ADPKD)
- Tolvaptan in its clinical trials
that lasted over a period of one year, in patients with later-stage
autosomal dominant polycystic kidney disease showed a decline in kidney
dominant polycystic kidney damage (ADPKD) is one of the most common and
potentially deadly forms of polycystic
it is known to affect many people in a single family.
- The requirement of dialysis or a
kidney transplant can either be delayed or postponed by taking tolvaptan
therapy in patients suffering from ADPKD.
, a condition with no cure,
in a phase 3 clinical trial testing
the efficacy and safety of the drug in ADPKD patients with late stage 2 to
early stage 4 CKD (chronic
belongs to a new class of medication called 'vaptan' drugs which blocks the
action of vasopressin receptors.
Tolvaptan is the
first available oral vasopressin receptor 2 antagonist which was approved by US
FDA in 2009 to be most commonly used in treating hypervolemia (excess fluid
retention) and hyponatremia (low blood sodium levels) in patients associated
with heart failure, cirrhosis, and syndrome of inappropriate antidiuretic
hormone (SIADH). However, FDA recommends that tolvaptan should not be used for
more than 1 month and it is not a drug of choice in patients with liver
ailments as tolvaptan may result in serious liver injury leading to liver
‘Tolvaptan’s effect of slowing the rate of kidney decline in patients with autosomal dominant polycystic kidney disease may make it a new treatment option in the future to help patients with this debilitating disease.’
Medicines Consortium (SMC) approved the use of tolvaptan in adults with ADPKD
followed by National Institute for Care and Clinical Excellence's (NICE) in
2015 that approved its use in England and Wales. Prior to the approval of
tolvaptan, there was no licensed drug to treat ADPKD in the United Kingdom.
Disease-Modifying Treatment for ADPKD with
underwent a phase 3, randomized, multicenter, placebo-controlled, double-blind
trial compared with a placebo.
been administered at an average dose of 95mg/day
for a three-year
duration. The change in the estimated glomerular filtration rate (GFR)
and the aminotransferase level
was recorded in the tolvaptan and the
At the end of
the trial, it was found that tolvaptan slowed the usual increase in kidney
volume by 50% and decreased the decline in kidney function by 30% in the
estimated GFR when compared to placebo
during a 12-month duration in
patients with later-stage autosomal dominant polycystic kidney disease.
The results of
the study deliver the necessity for a dialysis or a kidney transplant can be
postponed in patients with later-stage ADPKD, thereby increasing the quality of
Autosomal Dominant Polycystic Kidney Disease
ADPKD is a
genetic disorder which is a painful form of inherited polycystic kidney
disease. In this disease, fluid-filled cysts continue to develop and enlarge in
the kidneys eventually leading to kidney failure.
In some cases,
the affected polycystic kidneys are as large as the size of a football and
each kidney weighs around 30 pounds. The cysts may spread to other organs such
as liver or pancreas or seminal vesicles. Nearly 50% of patients with ADPKD
develop end-stage renal disease and require either dialysis or kidney
ADPKD can be done by performing ultrasound, CT or MRI scan. DNA testing such as
gene linkage testing or direct DNA sequencing can also be carried out to study
the family health status but come with the disadvantages of being costly
Symptoms of AKPKD
dominant polycystic kidney disease is found to be the fourth leading cause of
kidney disease and one of the world's most common dreadful genetic disease.
This disease is estimated to affect 7 to 17.5 million people worldwide (between
1 in 400 and 1 in 1000) occurring equally in both males and females and across
all races or ethnic groups.
- Vicente E. Torres, Arlene B. Chapman, Olivier Devuyst, Ron T. Gansevoort, Ronald D. Perrone, Gary Koch, John Ouyang, Robert D. McQuade, Jaime D. Blais, Frank S. Czerwiec, Olga Sergeyeva. Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease. New England Journal of Medicine, 2017; DOI: 10.1056/NEJMoa1710030
- Tolvaptan Phase 3 Efficacy and Safety Study in Autosomal Dominant Polycystic Kidney Disease (ADPKD) (TEMPO3:4) - (https://clinicaltrials.gov/ct2/show/NCT00428948)
- Tolvaptan - (https://en.wikipedia.org/wiki/Tolvaptan)
- What is ADPKD? - (https://pkdcure.org/what-is-pkd/adpkd/)
- Tolvaptan now recommended UK-wide for the treatment of ADPKD - (https://www.kidneyresearchuk.org/news/tolvaptan)
- Tolvaptan - (https://medlineplus.gov/druginfo/meds/a609033.html)
- What is ADPKD? - (http://www.pkdinternational.org/what-is-pkd/adpkd/)