What is ADPKD?

Autosomal dominant polycystic kidney disease (ADPKD) is a chronic condition that causes cysts to develop in the kidneys and sometimes elsewhere in the body. These cysts can cause various symptoms and they may cause the kidney to stop working properly.

How common is ADPKD?

About one person in every 1,000 has ADPKD, meaning approximately 25,000 Australians will be affected by ADPKD in their life. ADPKD occurs equally in males and females of all ethnic origin.

What causes ADPKD?

ADPKD is an inherited genetic disease.  It can be passed on from parents to their children through their genes. Genes are the instructions we need to make our cells, body parts and organs. We all have two copies of most genes, one from each of our parents. 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.

What are the symptoms of ADPKD?

Early in the progression of the disease there are generally no symptoms. In fact, many people are never diagnosed with ADPKD because they either have no symptoms or only a few symptoms that mimic other diseases. Common symptoms include:

High Blood Pressure also called hypertension, affects about 60% – 70% of men and 40% – 50% of women with ADPKD. It begins early in the course of ADPKD, often before there is abnormal kidney function. Left untreated, it further damages the kidneys, may enlarge the heart and can cause strokes.

Chronic pain or heaviness in the back, sides or abdomen is one of the most common problems for people with ADPKD. Pain can be intermittent and mild requiring only occasional pain medicine such as paracetamol. However, in a small number of people, the pain can be constant and quite severe.

Blood in the urine affects nearly 50% of those with ADPKD and can last for less than a day or a number of days. Bed rest, increased fluid intake and paracetamol for pain are usually the treatments if the bleeding is prolonged.

Urinary Tract Infection (UTI) is caused by bacteria reaching the bladder, kidneys or the cysts themselves. The most common symptom of UTI is pain or burning with urination and/or an urgent need to urinate even though there is only a small amount of urine. When the infection is in the kidney or in a cyst, there may be a sudden onset of fever, chills and back or flank pain.

Kidney stones occur in about 20%-30% of people with ADPKD, compared to 8%-10% in the general population. The symptoms are severe pain in the back, side or into the groin. Often there will be blood in the urine when passing a kidney stone.

Kidney cysts can sometimes become infected. This is usually very painful and typically accompanied by other symptoms, such as sweating, fever and high temperature. Cyst infections sometimes occur following a bladder or urinary tract infection (UTI). If you suspect you have a UTI, it is important to see your doctor and get treatment as soon as possible.

How is ADPKD diagnosed?

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

Diagnosis can involve a number of tests including:
  • Physical examination – may detect high blood pressure or enlarged kidneys
  • Ultrasound – the most common and least expensive test for PKD, sound waves detect cysts in the kidneys, even when they are quite small
  • Blood tests – may detect reduced kidney function
  • Urinalysis – blood and/or protein may be found in the urine
  • Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) – may be required if ultrasound results are inconclusive or more information is required, as they can detect very small cysts
  • Genetic testing – for families with a history of PKD, however these are not routinely performed

How will ADPKD affect my health?

ADPKD causes cysts (sacs filled with fluid) to develop in the kidneys. The cysts are not cancerous and the fluid inside them is harmless. In ADPKD, cysts typically begin to form in childhood and continue during adulthood. Over time they increase in size and number, causing the kidneys to enlarge. Cysts can eventually take over the kidneys to stop them from working properly and in about half of people affected, can lead to kidney failure, or ‘end-stage renal disease’. Cysts can also cause pain and other complications in the kidney.

ADPKD sometimes affects other parts of the body. People are affected differently, so not everyone will experience the effects listed here.

It is also important to remember that much can be done to help reduce, manage and treat the effects of ADPKD. Although the disease can have a significant effect on life, it does not mean that most people with the disease cannot live happy, long and productive lives.

At least 8 out of 10 people with ADPKD develop cysts in their liver. In most patients, liver cysts do not cause symptoms, or need treatment. About 1 in 20 people with liver cysts experience symptoms such as pain, feelings of ‘fullness’ and heartburn. Liver cysts are generally more common and worse in women than men, especially in women who have had more than one pregnancy and those who have used medicines containing oestrogen (mainly hormone replacement therapy)

Brain (or ‘intracranial’) aneurysms occur in around 1 in 10 people with ADPKD, which is around three- to four-times more common than in the general public. An aneurysm is a swelling, or bulge, in an artery caused by a weakness in the wall of the artery.

Brain aneurysms do not usually cause any symptoms. In a small number of people, the aneurysm can rupture, which can be disabling or even fatal. Because the risk for aneurysm is small, mainly people who have PKD and a family history of aneurysm are tested. Not everyone requires screening for this problem, but you should talk with your doctor to discuss this further.

Most people with ADPKD develop high blood pressure, which, left untreated, increases the risk of cardiovascular disease (such as heart attacks and strokes) and further damages the kidneys. Rarely, people with ADPKD may also have a higher risk of aneurysms in large blood vessels such as the aorta (which receives blood from the left ventricle of the heart and which branches to supply the head, neck and arms) and the coronary arteries (which supply the heart itself with blood).

Sometimes, though rarely, people with ADPKD have a heart valve problem called mitral valve prolapse (MVP). This occurs when one of the heart valves, called the mitral valve, does not work properly. This does not usually cause any symptoms or need treatment, and doctors are not recommended to test for this unless symptoms occur. Symptoms that can be associated with MVP are palpitations, a feeling that the heart is running away, there are extra beats in the heart or, chest pain that is not associated with exercise or exertion. Where treatment is needed, this can include lifestyle changes and, in severe cases, surgery.

Around 1 in 10 people with ADPKD have cysts in their pancreas, although these do not usually cause problems.

Abdominal hernias are more common in people with ADPKD. A hernia occurs when part of the body pushes through a weakness in the muscle that normally surrounds it. An abdominal hernia occurs in the abdomen or groin area. These should be surgically repaired if they are large or are causing problems, just as they would be in someone who does not have PKD.

Diverticular disease occurs when small bulges or pockets develop in the lining of the large intestine (bowel) and is more common among people with ADPKD with end-stage renal disease than among the general population. Often it does not cause symptoms or need treatment. Inflammation or infection of these pockets is called diverticulitis. The management of diverticulitis can involve laxatives, antibiotics and pain relief medication. This is a rare occurrence.

Seminal vesicles are glands that lie near the prostate. They are involved in the production of semen. Around 4 in 10 men develop cysts in the seminal vesicles, but these do not usually cause any symptoms or affect the sperm.

Erection problems are common in men with chronic kidney disease (especially end-stage renal disease), including that caused by ADPKD. Women and men with ADPKD can also experience sexual problems related to body image issues and discomfort caused by kidney enlargement.

What are the stages of ADPKD?

If you have kidney damage and/or a decrease in kidney function for three or more months, it is called chronic kidney disease (CKD). There are five stages of CKD.

Depending on the stage of your kidney disease, there are treatments and steps you can take to maintain your kidney health and overall quality of life.

Polycystic kidney disease usually develops slowly over many years, not everyone with PKD will progress to stage 5, or end stage kidney disease. By stage 5, your kidneys are in failure. When your kidneys are no longer functioning on their own, dialysis or a kidney transplant will be required.

Is there a cure for ADPKD?

Currently, there is no cure for ADPKD, which is why the PKD Foundation is raising money to fund medical research into finding a cure and raising awareness of the disease in Australia.

Is there any treatment for ADPKD?

In the early stages of ADPKD, there are ways to maintain kidney health. And there are many things that you are currently doing (or should be doing) that are very helpful for your kidneys and/or your general health. These include good blood pressure control (using medication if necessary, having a healthy diet (in particular minimising salt intake), maintaining a healthy weight and controlling your cholesterol.

You should do your best to reach these goals and work with your nephrologist to achieve the best outcomes. As each person’s experience is different, you should ask your doctor for more information. 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.

Vasopressin is a naturally occurring hormone which is released by the brain when it senses that the body is dehydrated (i.e. lacks water). When released from the brain, vasopressin enters the bloodstream and goes to the kidney where it tells the tubules of the kidney to reabsorb more water. This action then partly helps restore normal water balance to the body during times of mild dehydration, and it is a completely normal process. 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.

Tolvaptan may be of benefit to people with ADPKD who are at high-risk of developing kidney failure, some people with ADPKD may not need tolvaptan because they are low-risk. Kidney function is measured with a blood test called estimated glomerular filtration rate (eGFR). The normal eGFR is 90 ml/min or greater and indicates normal kidney function. In ADPKD, kidney function tends to stay normal for many years and in about 50% of patients does not change much at all.

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.

Two large international clinical trials each with more than 1000 patients (called TEMPO and REPRISE trials), showed that treatment of patients with ADPKD with tolvaptan slowed the decline in eGFR (kidney function) on average by about 1ml/min/1.73 m2 per year compared to those receiving placebo.

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.

Tolvaptan is recommended for some patients with ADPKD who are at high-risk of developing kidney failure. Not all patients require treatment with tolvaptan and this is a clinical decision that you should discuss with your nephrologist. In the REPRISE trial the impact was greatest in CKD Stage 3a, where the rate of decline in the untreated patients was 4.4ml/min/1.73 m2 per year, and in the group taking tolvaptan it slowed to 2.1ml/min/1.73 m2 per year. There was a similar impact in CKD Stage 2.  The benefit of tolvaptan is less with very advanced levels of kidney function and not recommended in these situations (i.e. Stage 4 or 5).

Although the trials showed benefit on kidney function decline, they were short in duration. It is not known whether long-term treatment with tolvaptan continues to slow the rate of renal function decline over many years, or if it will delay the need for dialysis or transplantation. The investigators have extrapolated from the data obtained in the REPRISE and TEMPO trials to suggest that tolvaptan may delay dialysis or transplantation for between 6 to 9 years. This is likely to be restricted to patients starting at the time of CKD Stage 2 or early Stage 3a.

Tolvaptan increases urine output in all patients because it blocks the action of vasopressin on healthy tubules of the kidney. This is not so much a side effect but arises directly from the way the drug works. On average, someone taking tolvaptan passes about 5-7 litres of urine per day. As a result, the frequency of urination increases, and on average this may be up to 20 x during day and 2-4 x during the night. Only about half of the people prescribed tolvaptan will tolerate this side effect in the first few weeks of starting the drug, and your doctor will monitor you closely and discuss ways to increase your chances of staying on the drug. 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.

  • Passing lots of urine and drinking lots of fluid to keep up with the lost urine
  • Need to see your kidney specialist regularly when you start treatment
  • Having monthly blood test for the first 18 months, and then 3-monthly while taking tolvaptan

You should talk with your nephrologist as to whether tolvaptan is suitable for you. If eligible, your nephrologist will know how to prescribe it for you.

Yes, several clinical trials using other treatments are in progress.

This is a very important question that everyone has been asking. Unfortunately, the clinical trials (REPRISE and TEMPO) using tolvaptan did not determine whether maintaining adequate water intake has the same effect as tolvaptan. Studies from the laboratory suggest that maintaining adequate hydration is beneficial for ADPKD and could do the same thing as tolvaptan.

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.

Your enrolment in a clinical will not affect your medical treatment. It’s important that you talk with your nephrologist and also notify the Investigators of your trial.

A significant proportion of people cannot tolerate tolvaptan. It is important to remember that many things that you are currently doing (or should be doing) are very helpful for your kidneys and/or your general health. These include good blood pressure control, having a healthy diet (in particular minimising salt intake), maintaining a healthy weight and controlling your cholesterol. You should do your best to reach these goals and work with your nephrologist to achieve the best outcomes.

Disclaimer: 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.