ADPKD is caused by an abnormality – often called a mutation or a variant – in one of the two genes involved in ADPKD. These genes are called PKD1 and PKD2. We each have two copies of the PKD1 gene and two copies of the PKD2 gene.
Autosomal dominant refers to the way the disease is inherited. Most people get the disease when they inherit an abnormal copy of a PKD1 or PKD2 gene from a parent with ADPKD. You only need to receive one abnormal copy of the gene to inherit ADPKD. If you have ADPKD, then there is a 1 in 2 (50 %) chance of passing the gene change on to each child you have (see inheritance diagram below). The risk of passing-on ADPKD is the same whether it is passed on by a mother or a father. The risk is also the same whether your child is male or female.
ADPKD does not skip a generation. If a child inherits the normal copy of the gene from an affected parent, then they will not develop the disease, and any children they go on to have will also be unaffected.
In some cases, ADPKD occurs when there is no family history. This may happen because the gene abnormality has arisen from a new genetic variant in a person with healthy parents who do not have the abnormal gene. This new variant can then be passed on to the next generation.
Someone reports a family history of ADPKD
Signs and symptoms that commonly occur in ADPKD appear
A test is done for another reason such as UTIs or kidney stones and cysts are found in the kidneys
While no cure currently exists for PKD, there is one pharmaceutical treatment known as Tolvaptan (JINARC®), approved in Australia and available on the Pharmaceutical Benefits Scheme (PBS) for eligible patients with ADPKD.
Tolvaptan (JINARC®) is a new treatment available in Australia for adults with ADPKD (autosomal dominant polycystic kidney disease) that can help slow the progression of ADPKD. Clinical trials have shown tolvaptan can slow the rate at which your kidneys become enlarged by cysts and can help to slow the rate at which your kidney function declines.
However, in adults with ADPKD, research has discovered that vasopressin also partly contributes to the growth of kidney cysts, by making them accumulate fluid.
Tolvaptan is a specific drug that is taken twice daily as a tablet. It blocks the effect of vasopressin in the body. In ADPKD it has been shown to slow cyst growth and reduce the decline in kidney function.
To qualify for tolvaptan (JINARC®), a person with ADPKD must:
– be older than 18 years old (not pregnant or breast-feeding) and
– have reduced kidney function (i.e. Stage 2 or Stage 3 chronic kidney disease (CKD) defined as an eGFR between 30-89 ml/min/1.73 m2) and
– have evidence that the kidney function (or eGFR) is declining (This is defined as a decline in eGFR of either 5ml/min/1.73 m2in 1 year or 2.5ml/min/1.73 m2per year over 5 years) and
– Measure liver function tests on a blood test before starting the drug (see below for reasons)
It is important to note that eGFR can fluctuate slightly from day-to-day and there can also be other reasons why someone’s eGFR is declining. Your nephrologist (kidney specialist) will be able to discuss this in more detail with you and advise you if tolvaptan is suitable for you.
In the TEMPO trial, tolvaptan also slowed the growth of kidney cysts (as measured by total kidney volume in MRI scans), but follow-up studies showed that the benefit might only occur in the first 1-2 years of taking the medication. The effect of tolvaptan on the growth of kidney cysts was not investigated in the REPRISE trial.
About 5% (one in twenty) of patients on tolvaptan develop abnormalities in the blood tests to assess liver function. These are typically mild and reversible when tolvaptan is stopped, but 1 in every thousand patients can develop more serious liver injury. For this reason, patients treated with tolvaptan must have their liver function tested every month for the first 18 months after starting the medication and then every 3 months while continuing on it.
Three people in hundred treated with tolvaptan may also experience mild gout due an elevation in blood levels of uric acid.
It is important to note a significant proportion of people cannot tolerate tolvaptan due to side effects.
However, we don’t know this for sure, and especially what amount of water is needed, and this is why a clinical trial in Australia (the PREVENT-ADPKD study) is evaluating this. Some individuals drinking excessive amounts of water or other liquids can develop low blood sodium, which can be dangerous. If you are thinking of drinking large volumes of liquid this should only be done after discussion with a doctor and with ongoing supervision.
The information provided here is an overview of Tolvaptan/JINARC® and does not contain all the available information nor does it take the place of talking to your doctor or pharmacist. All medicines have risks and benefits and your doctor will weigh the risks of you taking this medicine against the benefits they expect it will have for you.