Autosomal dominant polycystic kidney disease (ADPKD): PKD1, PKD2 and family testing

The PKD Charity explains that ADPKD is a condition some people are born with, caused by a gene usually inherited from a parent. It is not catching and not cancer. Fluid-filled pouches called cysts grow in the fine tubes of the kidneys and enlarge over time; the biggest can reach the size of a grapefruit and many are pea-sized. The kidneys can become very large and may eventually stop working properly, though the timing differs greatly from person to person, and some people never reach kidney failure.

The NHS Genomics Education Programme lists wider features: kidney stones, cyst bleeding and infection, liver cysts, diverticular disease, high blood pressure, heart valve problems such as mitral valve prolapse, widening of the aortic root, and intracranial aneurysm in about 10% of people where there is a family history. Chronic pain in the back, flank, abdomen and groin is present in up to 60%. The PKD Charity notes that most people with ADPKD (8 out of 10) have liver cysts by their mid-thirties, though the liver usually keeps working well.

Up to 85% of people have a harmful variant in PKD1 and up to 15% in PKD2. The NHS Genomics Education Programme says people with PKD2 typically reach kidney failure in their late seventies on average, whereas those with PKD1 usually reach it earlier, though variability is considerable, even within a family. Hypertension, a high body mass index and high salt intake are thought to affect progression.

Five other genes, including GANAB, DNAJB11, ALG5, ALG9 and IFT140, are linked to an ADPKD-like picture in 1% to 2% of patients. The programme adds that up to 40% of people with polycystic kidney disease and no family history have causative variants in genes other than PKD1 or PKD2, particularly younger patients, which is one reason genetic testing can help in unclear cases.

ADPKD is autosomal dominant. A person with ADPKD has one working and one changed copy of the gene, and each child has a 50% chance of receiving the changed copy. The PKD Charity repeats that if you inherited a gene change causing ADPKD there is a 1 in 2 chance of passing it on to each child, whichever parent has it.

The NHS Genomics Education Programme says ADPKD usually shows complete penetrance, so a person who inherits a harmful variant will in time have cysts, though how fast the disease progresses varies. After family screening about 10% of people are found to have no family history, and most of them probably represent new changes. The PKD Charity notes that a spontaneous gene change occasionally happens by chance before birth, so someone can have ADPKD although neither parent does.

Most diagnoses are made from typical ultrasound or MRI findings and a family history of cystic kidney disease, using age-specific criteria, according to the NHS Genomics Education Programme. Genetic testing may be warranted when there is no family history or the images are not typical, based on National Genomic Test Directory criteria. The programme also notes that the British Transplantation Society and the Renal Association recommend genetic testing and counselling for potential living related kidney donors, because it can help exclude the diagnosis with greater confidence.

The PKD Charity says people can have genetic testing for ADPKD for free on the NHS if they have, or are likely to have, the condition, with a sample of blood or saliva. Results can take from 6 weeks to 3 months, quicker if a family gene is already known, and about 1 in 4 people get an unclear result. A genetic counselling session helps people weigh the pros and cons. Its information also covers insurance questions and how pre-implantation genetic testing with IVF or, less often, testing in pregnancy might be used by those who wish to avoid passing ADPKD on.

Because ADPKD is generally a late-onset condition, the programme says genetic testing and counselling should be delayed until an appropriate age, at least 16.

Even though testing is generally delayed, the NHS Genomics Education Programme says there are important management points for children and young people. Early-onset high blood pressure should be addressed to slow kidney disease, and twice-yearly blood pressure checks should start between the ages of five and ten. Clinical guidelines for diagnosing and monitoring children with or at risk of ADPKD are available. The PKD Charity provides information on symptoms and testing in children and on talking to a child about ADPKD.

The first step in management is estimating when kidney failure might occur using tools such as the PRO-PKD score and the Mayo imaging classification, according to the NHS Genomics Education Programme. If the risk is high and disease is rapidly progressive, tolvaptan, a medicine that slows cyst growth, should be discussed. Careful blood pressure control with renin-angiotensin system inhibitors is the main way to protect kidney function, and other metabolic issues such as lipid disorders, diabetes and high body mass index should be addressed. Pain is treated to improve quality of life, and the need for a kidney transplant is assessed in good time. The programme says ADPKD does not recur in a transplanted kidney.

The PKD Charity adds that there is no cure, treatments help many symptoms, people have regular check-ups with their kidney doctor and GP throughout life, and many people eventually need dialysis or a transplant, though most people stay in good health for decades after diagnosis.