What is ADPKD?

Symptoms of PKD

Some people with PKD have no symptoms. When PKD patients do have symptoms, they can experience:

• Pain, typically in the lower half of the flank, lower back, or abdomen.
• Kidney stones: these are small, stone-like objects that form inside the kidneys. They can cause belly or side pain, or blood in the urine.
• High blood pressure: high blood pressure is a common feature of PKD, occurring in 60 to 70 percent of patients with normal kidney function by the age of 29. Over 90 percent of PKD patients will have high blood pressure by the time they reach end-stage kidney failure. Men tend to have higher blood pressures than women, and high blood pressure is associated with bigger kidneys and faster rates of kidney growth as PKD progresses.
• A bulging blood vessel in the brain: if the blood vessel bursts, it can cause a sudden, severe headache and nausea and vomiting. A burst blood vessel can lead to brain damage and even death.
• Cysts in the liver. These can cause belly pain, bloating, heartburn, shortness of breath, and back pain. Ruptured cysts can cause sharp, sudden abdominal pain, and if they become infected, they can also lead to fever, chills, and nausea.
• Cysts in the pancreas.
• A weak area in the abdominal muscles (called a “hernia”). This can cause an area of the belly to bulge out and can result in pain or discomfort with certain movements such as bending, lifting, or twisting.
• Urinary tract infections.
• Heart problems. 
   

Diagnosis of PKD

PKD can be diagnosed by any of the following measures/methods:

• Kidney imaging studies remain the mainstay for ADPKD diagnosis. Kidney ultrasound is commonly used for diagnosis. Sonographic diagnosis criteria for ADPKD are based on…
  • Age
  • Positive family history
  • Number of cysts
• Magnetic resonance imaging (MRI) or contrast-enhanced computed tomography (CT) can detect smaller cysts, and therefore, it can be used in high-risk patients with a normal or indeterminate ultrasound scan to confirm or rule out an ADPKD diagnosis
• Genetic testing is done to detect the mutations in genes known to be associated with ADPKD. This can be performed when a precise diagnosis is needed and the results of imaging testing are indeterminate. 

The method of diagnosis of ADPKD varies depending on the stage of the disease. However, establishing a definite diagnosis can be challenging due to the presence of similar symptoms in other disorders. Therefore, additional methods such as diagnostic imaging and genetic testing play a crucial role in confirming the diagnosis.

Imaging technologies such as ultrasound, computed axial tomography, and nuclear magnetic resonance are employed to identify cysts in the kidneys, liver, or pancreas. Magnetic resonance imaging has demonstrated higher sensitivity compared to ultrasound, enabling measurements such as height-adjusted total kidney volume, and providing clearer cyst definition without the need for contrast agents.

Yet, these imaging procedures come at a significant cost and are often omitted for certain subsets of the ADPKD population, such as young individuals at risk or patients with atypical or newly occurring cystic kidney disease. In these cases, genetic testing typically serves as the definitive diagnostic approach.

Current screening criteria states:

1. Two or more cysts as diagnostic for individuals ages less than 59
2. A minimum of four cysts in each kidney for older at-risk individuals.

The finding of fewer than two cysts in each kidney is sufficient to exclude the disease in people who are 30 or older.

Genetic Testing

Direct DNA sequencing (DS) presents an avenue for molecular diagnosis; however, the genetic analysis of PKD1 (the primary contributor to most ADPKD cases) is intricate. The 5'- region of the gene exists in multiple highly similar copies on chromosome 16. Currently, the ADPKD community endorses direct sequencing using a Long-Range PCR strategy with specific primers as the preferred approach. 

However, conducting isolated sequencing for each gene is time-consuming, expensive, and furnishes limited insights necessary for comprehensive diagnosis and prognosis. Furthermore, it's been observed that the primary disease-causing mutation might interact with other PKD or ciliopathy-related genetic loci, thereby influencing the phenotype and increasing the genetic intricacy of the condition. 

Consequently, ADPKD experts stress the importance of simultaneously screening all cystic genes under a unified strategy to achieve a more precise diagnosis, encompassing genes linked to atypical PKD forms. In this context, contemporary methodologies like next-generation sequencing followed by variant validation through DS have emerged as the recommended practice. These methods offer swifter, more cost-effective, and dependable genetic diagnoses for sizable ADPKD cohorts.

https://www.youtube.com/watch?v=NkQdoH6XC6w

Genetic Overview of Autosomal Dominant Polycystic Kidney Disease:

Approximately 80 percent of families with autosomal dominant polycystic kidney disease (ADPKD) have a mutation in the PKD1 gene, located on chromosome 16; these people have PKD1 disease. The remaining 15 percent have a mutation in the PKD2 gene on chromosome 4; this is called PKD2 disease.

In some cases, it is not possible to detect which gene is mutated. For example, PKD2 disease is typically milder than PKD1 disease; therefore, it often presents later in life and is sometimes not diagnosed at all. Because of this, the true prevalence of PKD2 disease is likely higher than the current estimate of 15 percent of all ADPKD patients.

Kidney failure occurs at an earlier age in PKD1 patients; the average age at which a patient reaches end-stage renal disease (that is, needing dialysis or a transplant) is approximately 55 years in PKD1 versus 74 years in PKD2 patients.

In approximately 10 to 15 percent of cases, ADPKD occurs in people without a family history of the disease (ie, family members have been evaluated and have no evidence for PKD). This is due to the patient having a new (de novo) genetic mutation that was not present in either parent.

Genetic Overview of Autosomal Recessive Polycystic Kidney Disease

Autosomal recessive polycystic kidney disease (ARPKD) is caused by mutations in the PKHD1 gene located on chromosome 6, which encodes fibrocystin (also referred to as polyductin), a large protein. Although the function of fibrocystin is currently unknown, it is found in different parts of the ducts in the kidney, in some parts of the bile ducts in the liver, and also in the pancreas and lungs.

The largest database for PKHD1 mutations contains more than 750 different mutations. Most patients with ARPKD are compound heterozygotes, who carry two different mutant alleles.

If you have polycystic kidney disease and you're considering having children, a genetic counselor can help you assess your risk of passing the disease to your offspring.

Management of PKD

Methods of PKD management:

• Find a nephrologist and care team who are knowledgeable about ADPKD. A collaborative, team approach is very valuable in PKD management.
• Learn about your tests and medications
• Control your blood pressure
• Drink plenty of fluids, such as water
  • Average recommended amount of water is three liter
  • Water acts as a flushing mechanism for bacteria
• Reduce salt intake
• Avoid a high protein diet
• Adopt a plant-based diet; the majority of your meals should come from plants
• Limit caffeine; can affect cyst growth
• Avoid drugs, medications, and agents that are potentially harmful to your kidneys
  • NSAIDs like motrin
  • PPIs - Proton Pump Inhibitors
  • IV contrast - CT scans, angiograms
  • MRI with IV contrast
  • Be cautious with OTC, herbal products, and supplements

PKD and Associated Intracranial Aneurysms

The most serious possible complication of PKD is a cerebral or brain aneurysm (a bulging blood vessel due to weakening of the blood vessel wall). Aneurysms can rupture, causing bleeding into the brain (subarachnoid hemorrhage). If not treated before the aneurysm ruptures, this can lead to irreversible brain damage or death. Aneurysm rupture occurs most often in people with larger aneurysms (>10 mm). The most common symptom of subarachnoid hemorrhage is a sharp, severe headache that begins suddenly, frequently with nausea and vomiting.

Approximately 3 to 7 percent of young adults with ADPKD may have brain aneurysms, and the frequency increases to 12 to 15 percent if someone else in the patient’s family has had an intracranial aneurysm. Compared with the general population, the risk of developing an aneurysm in ADPKD is approximately fivefold greater. People with a first-degree relative with a history of intracranial aneurysm or subarachnoid hemorrhage are at the highest risk of forming an aneurysm.

Early detection (before symptoms occur) of intracranial aneurysms is recommended in people who are considered high risk. Screening (looking for an aneurysm before it ruptures) is generally performed with magnetic resonance angiography (MRA) or, if not available, a computed tomography (CT) scan.

Routine screening is recommended only for high-risk patients, such as those with a previous rupture, a positive family history of a brain hemorrhage or stroke, or warning symptoms such as unusual, sudden headaches.

PKD and the Liver

Polycystic liver disease (PLD) is a rare condition that causes fluid-filled sacs called cysts to grow throughout the liver. A normal liver has a smooth, uniform appearance. A polycystic liver can look like a cluster of large grapes. Cysts can also grow independently in different parts of the liver. The cysts, if they get too numerous or large, may cause discomfort and health complications.

The majority of people with polycystic liver disease inherit the condition, but PLD can occur randomly with no genetic link. Women are affected more often than men and tend to have more cysts.

PLD is most common in people who have polycystic kidney disease (PKD), with its frequency increasing with age and progression of renal disease.

Most people don't discover they have PLD until they are adults, when the liver cysts become large enough to detect. Cysts can vary in size from no bigger than a pinhead to almost 4 inches in diameter. Likewise, your liver can stay its normal size or become extremely enlarged. Regardless of the number or size of cysts, polycystic livers typically continue to function normally and the disease is not considered life-threatening.

Most of the time, people with polycystic liver disease have no symptoms. However, if the liver becomes enlarged and covered with cysts, symptoms may include abdominal pain and bloating or swelling in the abdomen. 

One out of every 10 people with PLD develop associated symptoms or issues. In addition to severe abdominal pain, complications may include…

• Bleeding into a cyst
• Cyst rupture
• Infection of a cyst
• Yellowing of the skin and eyes due to resulting metabolic disorders

Because symptoms do not always occur, the majority of people learn they have PLD during a routine medical exam or diagnosis of kidney disease related to polycystic kidney disease.

Treatment is usually not needed unless you are experiencing PLD-related symptoms. Mild pain associated with PLD can be treated with pain medication. However, if the cysts cause significant discomfort or other complications, there are a number of treatment options available.

Cyst Aspiration: If a cyst is blocking a bile duct or if it has become infected, your doctor may recommend draining it. During cyst aspiration, your doctor, guided by ultrasound or CT imaging, will use a needle or catheter to drain the fluid in the cyst or cysts.

Cyst Fenestration: If you have large cysts on the surface of your liver, your doctor may suggest you have surgery to remove the wall of the cyst – a process called cyst fenestration.

Liver Resection: If the majority of cysts are in a particular area of the liver, your doctor may be able to surgically remove that part of the liver to provide pain relief and reduce the size of the liver.

Liver Transplantation: If liver resection is not possible or doesn't relieve your symptoms, a liver transplant may be an option. This treatment is typically reserved for people who are experiencing severe abdominal pain, have trouble eating, and whose overall quality of life is deteriorating.

PKD and Pregnancy

Your level of kidney function greatly affects your ability to conceive and to go on to have a successful pregnancy. If your kidney function is normal, your fertility is also likely to be normal. If your kidney function is severely impaired, the levels of reproductive hormones that your body produces may be considerably reduced, meaning that it could be harder to conceive.

Women with ADPKD are more likely to develop high blood pressure in pregnancy than women who don’t have ADPKD, particularly in later stages of pregnancy. If this occurs, you may be advised to start taking medication or increase your current medication to control your blood pressure. Remember any changes to your medication should only be made under close medical supervision.

Women with ADPKD are also more likely to develop pre-eclampsia. This is a condition in which women have protein in their urine, fluid retention, and high blood pressure. Pre-eclampsia is a serious condition for both the mother and the baby. Approximately 1 in 10 women with ADPKD and normal or mildly reduced kidney function develop pre-eclampsia. You could also be more likely to get pre-eclampsia if you already have high blood pressure or impaired kidney function.

Men with ADPKD usually have normal fertility, unless they have low kidney function. Men with severe ADPKD who have received a kidney transplant are typically fertile soon after transplantation. ADPKD can cause cysts in the reproductive system, but it’s uncommon for this to substantially affect fertility.

Pediatric PKD

ADPKD is caused by a faulty gene, which is usually inherited from a parent. If you have ADPKD, there is a one in two (50%) chance your child will inherit the disease. The risk is the same for every child you have.

Sometimes, a child can have ADPKD even if neither of their parents do. This occurs when a new genetic mutation develops in a child. However, this is quite rare.

Most children with ADPKD don't have symptoms that cause problems. Their kidney cysts are only just beginning to form and there is plenty of normal, healthy kidney tissue available to filter their blood.

Some children can still experience symptoms, including:

• Pain in the sides or back
• Urinary tract infections
• Kidney stones
• Passing more urine than normal (this can happen even with small cysts)
• Frequent urination (polyuria)
• Blood in the urine
• About 25% of children with ADPKD get high blood pressure, but this usually doesn't cause immediate symptoms. It is important that your child's blood pressure is monitored and treated if it becomes elevated.

Signs that a child might have ADPKD that progresses quickly include having enlarged kidneys or high blood pressure. Therefore, routine monitoring of the disease progression is crucial.

Nutrition Recommendations for Patients with PKD

Nutrients to Avoid:

• Sodium: Excess sodium can increase blood pressure, so it is important to reduce salt intake as much as possible.
• Caffeine: It may promote cyst growth.
• Processed foods: These foods are usually high in salt and sugars.
• Corn Syrup: It is a form of liquid calories and should be avoided.

Nutrients to Reduce Intake Of:

• Carbohydrates: They should be eaten in moderation as they are caloric and can lead to weight gain.
• Protein: Your doctor may recommend a lower intake of protein depending on your level of kidney function. Since the kidneys process protein, it is difficult for them to filter it out when their function is diminished. This can then cause a backup of excess waste in the blood.
• Alcohol: It should be consumed in moderation. Drinks with high sugar content should be avoided.

Recommended Nutrients

• Fibers: They help assist the body with digestion.
• Fruits and Vegetables: These foods are lower in calories and can help lower blood pressure. However, you should be aware of potassium content in this food group and talk to your doctor regarding any potassium restrictions.

Disclaimer: The UCLA Health System cannot guarantee the accuracy of such information. The information is provided without warranty or guarantee of any kind. Please speak to your Physician before making any changes.