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Autosomal dominant polycystic kidney disease
Also known as Autosomal dominant polycystic kidney disease (PKD1) · Autosomal dominant polycystic kidney disease (PKD2)
ADPKD is a common inherited kidney condition where cysts develop in the kidneys, leading to their enlargement and often impairing kidney function over time. It can also affect other organs and is caused by changes in the PKD1 or PKD2 genes.
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Overview
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a progressive genetic disorder that mainly affects the kidneys. It is characterised by the development of multiple fluid-filled sacs, known as cysts, within the kidneys. These cysts can grow over time, leading to significant enlargement of the kidneys and gradual decline in kidney function [PMID:33671754]. ADPKD is one of the most common inherited kidney conditions, affecting between 1 in 400 and 1 in 1,000 people, making it a significant cause of chronic kidney disease and kidney failure.
While ADPKD primarily impacts the kidneys, cysts can also form in other organs, such as the liver, pancreas, and seminal vesicles. The condition is termed 'autosomal dominant' because a person only needs to inherit one copy of an altered gene from a parent to develop the condition. Symptoms and disease progression can vary considerably among individuals, even within the same family, making personalised management important.
Symptoms & clinical features
The symptoms of ADPKD often develop gradually and may not become apparent until adulthood, typically between 30 and 50 years of age. Some individuals, however, may experience symptoms earlier or later in life. Early symptoms can be subtle and might include pain in the back or sides, which can be due to the growing cysts or kidney stones [PMID:33671754].
As the condition progresses, individuals may experience a range of symptoms related to impaired kidney function. These can include high blood pressure (hypertension), blood in the urine (haematuria), frequent urinary tract infections, and abdominal pain or swelling due to enlarged kidneys. Fatigue, loss of appetite, and nausea can also occur as kidney function declines. In some cases, a person might discover they have ADPKD incidentally during imaging for another health concern.
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Affected organs
The kidneys are the primary organs affected by ADPKD. Over time, the numerous cysts can cause the kidneys to become much larger than their normal size, sometimes weighing several kilograms each. This enlargement and the pressure from the cysts lead to a reduction in the kidneys' ability to filter waste products from the blood, ultimately resulting in chronic kidney disease and potentially kidney failure.
Beyond the kidneys, cysts commonly develop in the liver (hepatic cysts), which can become very numerous and large, though they usually do not affect liver function as severely as kidney cysts affect kidney function. Cysts may also form in the pancreas and seminal vesicles. Other potential complications include brain aneurysms (weakened blood vessel walls), which can sometimes rupture, and heart valve abnormalities, particularly mitral valve prolapse [PMID:33671754]. Diverticula (small pouches) in the large intestine are also more common in individuals with ADPKD.
Risks & severity
The severity and progression of ADPKD can differ significantly between individuals. While some people may experience only mild symptoms throughout their lives, others may face kidney failure relatively early. Approximately 50% of individuals with ADPKD will develop end-stage renal disease (ESRD) by the age of 60, requiring dialysis or a kidney transplant [PMID:33671754]. The age of onset for symptoms typically ranges from 30 to 50 years, but there can be cases of earlier or later presentation.
Factors that may influence the severity and progression of ADPKD include the specific gene affected and the type of genetic change, as well as environmental and lifestyle factors. For instance, changes in the PKD1 gene are generally associated with a more severe course and earlier onset of kidney failure compared to changes in the PKD2 gene. Complications such as uncontrolled high blood pressure, recurrent urinary tract infections, and rupture of cysts can also contribute to disease progression and increased discomfort.
Genetic causes
ADPKD is caused by pathogenic changes (sometimes called mutations) in either the PKD1 or PKD2 gene. The PKD1 gene encodes a protein called polycystin-1, which is a large transmembrane protein involved in cell signalling and cell-to-cell and cell-to-matrix interactions within the kidneys. This protein plays a crucial role in maintaining the normal structure and function of kidney tubule cells [PMID:33671754].
The PKD2 gene produces polycystin-2, a protein that functions as a transient receptor potential (TRP) cation channel. Polycystin-2 often interacts with polycystin-1, and together they are involved in regulating cellular processes such as cell growth, differentiation, and fluid secretion. Pathogenic changes in either PKD1 or PKD2 disrupt the normal function of these proteins, leading to abnormal cell proliferation and fluid secretion within kidney tubules, which ultimately results in cyst formation [PMID:33671754]. Changes in PKD1 are responsible for about 85% of ADPKD cases, while changes in PKD2 account for around 15%. Generally, changes in PKD1 tend to lead to a more severe form of the disease.
- PKD1 polycystin 1, transient receptor potential channel interactingThe *PKD1* gene provides instructions for making polycystin-1, a protein crucial for normal kidney development and function, with pathogenic variants causing Autosomal Dominant Polycystic Kidney Disease.
- PKD2 polycystin 2, transient receptor potential cation channelThe PKD2 gene provides instructions for making polycystin-2, a protein vital for kidney development and function, particularly through its role as an ion channel.
Inheritance pattern
ADPKD follows an autosomal dominant inheritance pattern. This means that a person only needs to inherit one copy of an altered gene (either PKD1 or PKD2) from one parent to develop the condition. If a parent has ADPKD, each of their children has a 50% (1 in 2) chance of inheriting the altered gene and therefore developing the condition, regardless of their sex.
It is important to understand that ADPKD can also occur without a family history in approximately 5-10% of cases. These are known as de novo (new) pathogenic changes, meaning the alteration occurred for the first time in the affected individual and was not inherited from either parent. However, once a de novo change has occurred, that individual can then pass the altered gene on to their children in an autosomal dominant manner.
Each child of an affected parent has a 50% chance of inheriting the pathogenic variant, regardless of sex.
Subtypes & variants
This page covers Autosomal dominant polycystic kidney disease as a single condition. Several distinct variants and clinical subtypes are recognised in the literature - they share the underlying biology and broad management approach, but differ in severity, age of onset, or causative gene:
- PKD1 (~85% of cases) PKD1 OMIM 173900
PKD1 accounts for roughly 85 per cent of ADPKD. Earlier onset of cyst burden, faster decline in kidney function, and typical kidney failure between ages 50 and 60.
- PKD2 (~15% of cases) PKD2 OMIM 613095
PKD2 accounts for roughly 15 per cent of ADPKD. Slower disease progression, lower cyst burden, and typical kidney failure delayed to ages 60 to 70 or later.
Diagnosis & testing
Diagnosis of ADPKD is typically based on a combination of clinical symptoms, family history, and imaging studies, primarily ultrasound or MRI of the kidneys. Imaging can detect the characteristic multiple cysts in the kidneys. Diagnostic criteria often consider the number of cysts and the patient's age [PMID:28751554]. For example, a person with a family history of ADPKD aged 30-39 years might be diagnosed if they have at least 2 cysts in each kidney.
Genetic testing can confirm a diagnosis of ADPKD, especially in cases where imaging results are inconclusive, there is no clear family history, or for pre-symptomatic testing in at-risk individuals. Genetic testing can identify pathogenic changes in the PKD1 or PKD2 genes. In the UK, genetic testing for ADPKD is available through the NHS Genomic Medicine Service (GMS) under specific R-codes, such as R189 for ADPKD. Referrals for genetic testing are typically made by nephrologists or clinical geneticists, often after a discussion with a genetic counsellor.
Management & lifestyle
Managing ADPKD focuses on slowing disease progression, controlling symptoms, and managing complications. There is no cure for ADPKD, but treatments are available to manage its effects. Lifestyle modifications, such as maintaining a healthy blood pressure, staying hydrated, and avoiding excessive salt intake, are generally recommended. Management often includes close monitoring of kidney function and blood pressure.
Medications, such as vasopressin receptor antagonists (e.g., tolvaptan), may be prescribed to slow the rate of decline in kidney function in some adults with rapidly progressing ADPKD. Pain management strategies are also important, ranging from over-the-counter pain relievers to more targeted interventions for cyst-related pain. If kidney failure occurs, treatment options include dialysis or kidney transplantation. Regular follow-up with a nephrologist (kidney specialist) is a key part of the care pathway, and individuals may also benefit from consultations with other specialists, such as genetic counsellors, to understand the condition and its implications for family planning.
UK care pathway
In the UK, individuals with suspected or confirmed ADPKD are typically managed within the NHS. The care pathway generally begins with a referral to a nephrologist for specialist kidney care. Genetic counselling forms an integral part of this pathway, providing information about the condition, its inheritance, and implications for family members. Genetic testing for ADPKD is available through the NHS Genomic Medicine Service (GMS) under specific R-codes, such as R189 (ADPKD - targeted gene testing), which helps to confirm the diagnosis and can inform prognosis and family planning. These tests are typically requested by clinical geneticists or nephrologists following a thorough clinical assessment.
Frequently asked questions
Will my children inherit ADPKD?
If you have ADPKD, each of your children has a 50% (1 in 2) chance of inheriting the altered gene and developing the condition. This is because ADPKD has an autosomal dominant inheritance pattern. Genetic counselling can provide more personalised information and discuss testing options for family members.
What is the difference between PKD1 and PKD2?
Both PKD1 and PKD2 are genes that, when altered, cause ADPKD. Changes in PKD1 are more common and generally lead to a more severe form of the disease with earlier onset of kidney failure. Changes in PKD2 typically result in a milder form of ADPKD, with kidney failure often occurring later in life, if at all.
Can ADPKD affect organs other than the kidneys?
Yes, while the kidneys are primarily affected, ADPKD can also cause cysts to form in other organs, most commonly the liver. Less frequently, cysts can appear in the pancreas or seminal vesicles. There is also an increased risk of brain aneurysms and certain heart valve problems.
Is there a cure for ADPKD?
Currently, there is no cure for ADPKD. However, treatments are available to manage symptoms, slow the progression of kidney disease, and address complications. These include lifestyle modifications, medications to preserve kidney function, and ultimately dialysis or kidney transplantation if kidney failure occurs.
How is ADPKD diagnosed?
Diagnosis typically involves a combination of your medical history, family history, and imaging tests like ultrasound or MRI to visualise kidney cysts. Genetic testing can also be used to confirm the diagnosis, particularly in unclear cases or for at-risk family members, and is available through the NHS Genomic Medicine Service.
References
- Torres VE, Harris PC, Pirson Y. Autosomal dominant polycystic kidney disease. Lancet (London, England). 2007. PMID: 17434405
- Irazabal MV, Torres VE. Total Kidney Volume and Autosomal Dominant Polycystic Kidney Disease: A Long-Standing Relationship. American journal of nephrology. 2018. PMID: 30071513
- Zieneldien T. The autosomal road. Journal of nephrology. 2026. PMID: 42640558
- Polubothu S, Richardson A, Kerecuk L. Autosomal dominant polycystic kidney disease in children. BMJ (Clinical research ed.). 2016. PMID: 27266528
- van Gastel MDA, Meijer E. To Add Weight to Overweight. Clinical journal of the American Society of Nephrology : CJASN. 2021. PMID: 34117079
- Pei Y, Watnick T. Autosomal dominant polycystic kidney disease. Advances in chronic kidney disease. 2010. PMID: 20219614