What is Autosomal Dominant Polycystic Kidney Disease?
Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of kidney failure around the world. ADPKD is an inherited disorder that progressively affects multiple systems of the body. It causes the formation of cysts in the kidneys, enlargement of the kidneys, and can also affect other organs like the liver, pancreas, spleen, heart, and membranes covering the brain and spinal cord.
In adults, ADPKD can occur in any race and it’s the reason why 6% to 10% of all dialysis patients in the U.S. need treatment. The disease might start to develop in children or even babies in the womb, but generally, symptoms don’t show up until the person is in their 30s or 40s.
Autosomal recessive polycystic kidney disease (ARPKD), on the other hand, is very rare. It affects 1 in 20,000 – 40,000 newborns. Unlike ADPKD, ARPKD often has a more severe impact and is caused by mutations in a specific gene which produces a protein called fibrocystin. ARPKD usually shows up in childhood and unfortunately, can often lead to death in children or even in newborns.
What Causes Autosomal Dominant Polycystic Kidney Disease?
ADPKD is a condition caused by changes in several genes. Two of these genes, PKD1 and PKD2, have been identified. The PKD1 gene, located on chromosome 16p13.3, is responsible for 85% of ADPKD cases. The remaining 15% are due to the PKD2 gene, located at 4q21. There’s also another gene known as GANAB. It’s believed that changes in this gene contribute to 1% of ADPKD cases, often causing a more variable form of polycystic liver disease.
It’s interesting to note that changes in both PKD1 and PKD2 result in similar physical symptoms. However, these two genes do affect the body differently. When the PKD1 gene is altered, about half of the patients require kidney replacement therapy by the time they’re 60. On the other hand, changes in the PKD2 gene are often seen in older individuals and cause a milder form of the disease. This milder form is characterized by fewer kidney cysts, hypertension that begins late in life, and less severity of end-stage kidney disease compared to when PKD1 is mutated.
Risk Factors and Frequency for Autosomal Dominant Polycystic Kidney Disease
ADPKD is a global disease that affects all races. It has a rate of diagnosed cases that ranges from 1 in 400 to 1 in 1,000. Some people with ADPKD may not show any symptoms throughout their lives. However, ADPKD is not a harmless disease, as around half and potentially up to three-quarters of all people with ADPKD develop a severe form of kidney disease, known as end-stage kidney disease (ESKD), by the time they reach 70 years of age. This constitutes up to 10% of all patients with ESKD.
In the United States, between 1998 to 2001, the numbers of men and women with ESKD caused by ADPKD were 8.7 and 6.9 per 1 million population, respectively. Comparatively, during the same time period, Europe and Japan recorded rates of 7.8 and 6.0 per million, and 5.6 and 4.0 per million individuals respectively. The worldwide total number of people with ADPKD is approximately 12.5 million.
Thanks to better awareness, early detection, and improved treatment for high blood pressure, people with ADPKD are developing ESKD at an older age, and fewer people are dying from the disease. Kidney disease from ADPKD tends to be more severe in men, while polycystic liver disease, usually associated with ADPKD, occurs more frequently in women, hinting that hormone levels may play a role in these conditions.
Signs and Symptoms of Autosomal Dominant Polycystic Kidney Disease
Autosomal dominant polycystic kidney disease (ADPKD) is a condition that can affect many different parts of the body, like the kidneys and the liver. Although kidney function can stay normal for a long time, once it starts to worsen, the decline can be quite fast.
There are several factors that can make the prognosis worse. These include being male, having high blood pressure at a young age, having a specific genetic marker (PKD1), having increased total kidney volume, and having protein in the urine. The size of the kidneys can often predict future loss of kidney function.
ADPKD can cause a variety of symptoms, including high blood pressure, anemia, liver cysts, blood in the urine, side pain, abdominal masses, urinary tract infections, kidney failure, kidney stones, and kidney cancer.
- High blood pressure is often the earliest symptom.
- Protein and blood in the urine are also common.
- Sudden side pain can occur due to bleeding into a cyst or a tumor.
- Blood in the urine can also occur when a cyst bleeds into the urinary system, and this can be mistaken for a cyst infection because it can cause a fever.
- Urinary tract infections are common, including bladder infections, kidney infections, cyst infections, and abscesses around the kidneys. These are often caused by bacteria like Escherichia coli and Klebsiella.
- Kidney stones occur in about 20-25% of people with ADPKD, and can be caused by low urine volume, slow urine flow due to blockages, hypocitraturia (low citrate in urine), and low magnesium in the urine. These stones can be hard to diagnose because of the existing calcifications in ADPKD patients’ kidneys.
Liver cysts are also common in ADPKD and become more frequent with age. If there are 4 or more cysts seen in the liver, it could be an evidence of polycystic liver disease. Although these can often be symptom-free, they can sometimes cause liver damage or pain due to infection or rupture. Some ADPKD patients may also have pancreatic cysts.
Heart abnormalities like mitral valve prolapse and aortic regurgitation are also common. Other heart issues can include coronary aneurysms, asymptomatic pericardial effusions, congenital heart malformations, aortic valve stenosis, and atrial fibrillation. Gastrointestinal issues such as diverticulosis can affect up to half of ADPKD patients.
Children with ADPKD may not have kidney impairment, but can have higher rates of high blood pressure and protein in the urine, which require careful monitoring and treatment. Diagnosing ADPKD in children can sometimes be challenging.
Testing for Autosomal Dominant Polycystic Kidney Disease
Autosomal dominant polycystic kidney disease (ADPKD) can usually be diagnosed based on a family history of the disease, ultrasound or CT scan imaging, and symptoms such as high blood pressure or kidney failure. Multiple cysts on both kidneys, as shown in a CT scan or renal ultrasound, could also indicate ADPKD, even without a family history of the disease.
Ultrasound imaging is usually enough for patients who don’t show any symptoms and have normal kidney function. But in children, if the first ultrasound doesn’t show any kidney cysts, additional ultrasounds should be done when the child reaches adolescence (between ages 15 and 18).
If the disease’s progression needs to be monitored, or if the risk of the disease worsening must be estimated, CT or MRI scans may be used. These scans can also be helpful in managing possible future complications, tracking the progression of the disease, and spotting kidney stones early.
Experts recommend that parents or caregivers of individuals with ADPKD should be informed about the chances of the condition being passed down. It’s also recommended that children and young adults who are at risk should have their blood pressure checked every two years.
Genetic testing for ADPKD is available and has a 99% accuracy rate. This test can be useful for young adults who don’t show any signs of ADPKD on ultrasound but have a family history of the disease, especially if they’re considering donating a kidney, having children, or getting pregnant. Genetic testing can also help to confirm an ADPKD diagnosis when the symptoms and imaging results aren’t clear cut.
The decision to undergo genetic testing or renal ultrasonography for children without symptoms should be made jointly by caretakers, parents, and healthcare professionals.
There are specific criteria for diagnosing ADPKD using ultrasound. For example, from ages 15 to 29, a person must have 2 or more cysts, in one or both kidneys. From ages 30 to 59, they should have 2 or more cysts in each kidney. And for those aged 60 and above, they should have 4 or more cysts in each kidney. These criteria can accurately predict the presence of ADPKD.
It’s important to note the difference between Autosomal Dominant and Autosomal Recessive Polycystic Kidney Disease. In the dominant variant, symptoms typically begin at age 30 and the disease is relatively common. Liver cysts might develop but they usually don’t lead to significant liver disease. The disease is usually inherited and life expectancy can range from 53 to 70 years. Kidney disease usually develops in patients in their 60s.
In contrast, the recessive variant of the disease usually begins at birth and is relatively rare. Liver cysts develop early and can lead to severe liver disease. There’s usually no family history of this disease and many patients will die early, within the first month. However, those who survive past the newborn period have a 90% chance of living to at least 20 years. Half of the patients who reach the age of 20 will develop end-stage kidney disease.
Treatment Options for Autosomal Dominant Polycystic Kidney Disease
The Mayo classification system for kidney diseases ranks patient conditions from least to most severe. This system helps identify high-risk patients who could benefit most from aggressive treatment options. Among the various classification factors, the total size (volume) of the kidney is most useful for diagnosis.
Several lifestyle and dietary changes are often recommended for patients, although they may not completely prevent disease progression. Patients are generally advised to stay well-hydrated and limit sodium intake to help improve their blood pressure and potentially reduce kidney volume.
Dealing with symptoms like flank pain involves excluding other possible causes like infection, kidney stones, and certain types of cancer and neural disorders. To manage the pain, patients can consider medications, ultrasound-guided cyst aspiration, or surgical intervention, depending on the severity and cause of their symptoms.
Patients typically respond well to conservative treatment for cyst hemorrhage, a condition where the kidney cysts bleed. Severe cases might require hospitalization, blood transfusions, and extra care.
Cyst and urinary tract infections need immediate treatment to prevent further damage. Doctors often prescribe antibiotics that can reach the cysts effectively. If the infection persists despite medication, doctors might need to drain the infected cysts surgically.
Patients with this disease are more likely to develop kidney stones. The common treatments include potassium citrate, high fluid intake, and careful monitoring of patients’ urine to identify potential risk factors.
Controlling high blood pressure is crucial to prevent further damage. Doctors usually recommend angiotensin inhibitors unless the patient has a specific condition that prevents their use. Alternatives may include beta-blockers, calcium-channel blockers, and certain diuretics.
Tolvaptan, an FDA-approved medicine, can aid the slowing of disease progression by blocking certain kidney cell receptors. However, due to its potentially harmful side effects, doctors generally recommend it for patients with rapidly declining kidney function and fewer additional health conditions.
Doctors may remove one or both kidneys if the patient experiences severe symptoms like unbearable discomfort, uncontrolled infection or bleeding, or kidney cancer. When kidney function is lost entirely, the treatment includes dialysis or kidney transplantation.
Researchers continue to investigate potential future treatments for this disease. Promising areas of study include medicine that blocks renal pathways related to cell proliferation and kidney cyst formation and substances derived from spices that could suppress inflammation and control cell growth.
What else can Autosomal Dominant Polycystic Kidney Disease be?
Kidney cysts can appear in several other medical conditions as well.
Bardet-Biedl syndrome is a multifaceted genetic disease which often involves problems with sight, weight issues, and kidney complications. One of the symptoms that can crop up are these kidney cysts, but it’s important to note that they aren’t the only symptom.
HNF1B mutations can cause kidney cysts. These are typically seen alongside a multitude of different body-wide health disorders such as diabetes and gout that appear early in one’s life, underdeveloped pancreas, malfunctioning liver, and issues with the reproductive tract.
Medullary sponge kidney disease is a rare, hereditary disease (appearing in 1 out of every 5,000 individuals) that results in the formation of small kidney cysts or the widening of renal collecting tubules. Although this can result in structures resembling cysts in the kidney, it doesn’t typically lead to kidney failure. However, it is closely linked to conditions like nephrocalcinosis and nephrolithiasis, usually due to low citrate in urine and high calcium in urine. It’s also linked to a higher risk of urinary tract infections.
The orofaciodigital syndrome type I is a genetic problem marked by varied abnormalities appearing in the face, mouth, and fingers. While kidney conditions including cysts, can occur, they’re not typically the main factor for diagnosis.
Kidney cysts can notably appear in tuberous sclerosis. However, this disorder is generally associated with recognizable skin abnormalities, facial skin growths, connective tissue birthmarks, and symptoms affecting the heart, kidney, and lung.
Various conditions that doctors consider when diagnosing Autosomal Dominant Polycystic Kidney Disease (ADPKD) include:
* Autosomal dominant tubulointerstitial nephropathy
* Autosomal recessive polycystic kidney disease
* Bardet-Biedl syndrome
* HANAC syndrome
* HNF1B mutations
* Medullary sponge kidney
* Multiple simple renal cysts
* Orofaciodigial syndrome type I
* Parapelvic renal cysts
* Renal spongiosis
* Tuberous sclerosis
* Von Hippel-Lindau syndrome
What to expect with Autosomal Dominant Polycystic Kidney Disease
Around half of patients with ADPKD, a type of kidney disease, will experience severe kidney failure by the age of 70. In some cases, this might rise to as much as 75%.
In a study carried out in Canada, it was found that 25% of patients with ADPKD had severe kidney failure by 47 years, 50% by 59 years, and 75% by 70 years.
Meanwhile, a French study reported that 22% of patients with ADPKD had severe kidney failure by 50 years old, 42% by 58 years old, and 72% by 73 years old.
Typically, the life expectancy for patients with ADPKD ranges from 53 to 70 years.
Possible Complications When Diagnosed with Autosomal Dominant Polycystic Kidney Disease
The major problems associated with ADPKD (a kidney disease) include reaching a stage where dialysis or a kidney transplant is required. Another severe issue is the bursting of a cerebral aneurysm, which is particularly common in ADPKD patients. This risk becomes higher for people with a personal or family history of cerebral aneurysm or subarachnoid hemorrhage, women, and older individuals. On top of this, risk factors that can be controlled include smoking, high blood pressure, and excessive drinking.
Furthermore, liver cysts are also a possible complication of ADPKD. The frequency of this increases with age, with about 10% to 20% of people under 30 years having it, while it reaches up to 50% to 70% in those who are over 60. This rarely impacts the functioning of the liver but can be related to liver discomfort due to bleeding or infection in the cyst.
Finally, ADPKD often comes along with other issues too, such as diverticular disease, kidney stones, and abdominal wall or inguinal hernias.
- The end-stage kidney disease that requires dialysis or renal transplantation
- A ruptured cerebral aneurysm
- Smoking, hypertension, and excess alcohol intake
- Age-related increase in liver cysts
- Diverticular disease
- Kidney stones
- Abdominal wall or inguinal hernias
Preventing Autosomal Dominant Polycystic Kidney Disease
After being diagnosed, it’s important for patients to have regular check-ups with kidney specialists, or nephrologists. By identifying the disease early, evaluating risks, using the right medications, and managing the factors that commonly lead to kidney stones, high blood pressure, and protein in urine, disease progression can be slowed down.
Simple lifestyle changes can also be very beneficial in the long run. These include drinking more water, limiting salt in the diet, and avoiding certain painkillers known as NSAIDs.
