Polycystic Kidney Disease (PKD)

How PKD develops

In ADPKD, mutations in the PKD1 gene (about 75% to 80% of cases, usually more severe) or PKD2 gene disrupt proteins in the kidney tubule cells. Tubules widen into cysts that fill with fluid and gradually expand. Over decades, millions of cysts replace normal tissue. Kidneys can grow to several times their normal size and weight.

Kidney function usually stays normal for years, because healthy tissue compensates, then declines more steeply, often from the 40s.

Types

About 10% of ADPKD cases arise from new mutations with no family history.

Symptoms

• high blood pressure, often the first sign, sometimes before age 30
• back or flank pain, dull or sharp
• blood in the urine (from cyst bleeding)
• kidney stones
• urinary tract and cyst infections
• a fuller or enlarged belly
• frequent urination and passing urine at night
• tiredness and other symptoms of chronic kidney disease as function declines

Problems outside the kidneys

• liver cysts: very common, especially in women, usually harmless but sometimes large
• brain aneurysms: more common than in the general population, especially with a family history of aneurysm or brain bleed
• heart valve changes: mitral valve prolapse
• abdominal wall and groin hernias
• diverticular disease
• pancreatic and seminal vesicle cysts

Diagnosis

• ultrasound: the usual first test. Age-specific criteria based on the number of cysts confirm ADPKD in people with a family history
• MRI: measures total kidney volume, which predicts how fast disease will progress (Mayo imaging classification)
• genetic testing: useful when imaging is unclear, there is no family history, or for potential living kidney donors
• kidney function tests (eGFR) and urine tests
• brain MRA screening for aneurysms in people with a family history of aneurysm or brain bleed, or high-risk jobs

Treatment

Slowing progression

• blood pressure control: ACE inhibitors or ARBs. A target of 110/75 or lower is recommended for younger patients with preserved kidney function, based on the HALT-PKD trial, when tolerated
• tolvaptan: a vasopressin receptor blocker that slows kidney growth and function decline in people at risk of rapid progression. It causes heavy thirst and urination and needs regular liver tests
• drink plenty of water spread through the day (unless advised otherwise)
• low-salt diet
• healthy weight, exercise and not smoking
• avoid NSAIDs such as ibuprofen, which can harm the kidneys

Managing symptoms and complications

• pain management with acetaminophen (paracetamol), heat and, for severe cases, cyst drainage or nerve procedures
• antibiotics that penetrate cysts for infected cysts
• treatment of kidney stones
• management of chronic kidney disease: anemia, bone health and acid balance

Kidney failure

Dialysis or kidney transplant. People with PKD do well after transplant, since the new kidney does not develop cysts. Very large kidneys may need removal to make room.

Outlook

The course varies widely, even within families. People with PKD2 mutations generally progress more slowly and reach kidney failure later than those with PKD1. Many people with ADPKD live long lives, especially with good blood pressure control and modern treatments.

Frequently asked questions

What are the first signs of polycystic kidney disease?

High blood pressure, often at a young age, is frequently the first sign. Others include back or side pain, blood in the urine, kidney stones and urinary tract infections. Many people have no symptoms for years.

Is polycystic kidney disease hereditary?

Yes. ADPKD is autosomal dominant, so each child of an affected parent has a 50% chance of inheriting it. ARPKD is recessive. About 10% of ADPKD cases come from new mutations.

What is the life expectancy with polycystic kidney disease?

Many people with ADPKD live into their 70s or beyond, especially with good care. About half reach kidney failure by around age 60, after which dialysis or a transplant can extend life significantly.

Can polycystic kidney disease be slowed?

Yes. Tight blood pressure control, tolvaptan for people at risk of rapid progression, drinking plenty of water, a low-salt diet, healthy weight and avoiding NSAIDs can slow kidney growth and loss of function.

Should family members be tested for PKD?

Adult relatives can discuss screening with a doctor. An ultrasound or genetic test can detect PKD, allowing early blood pressure monitoring. The decision is personal, as a diagnosis can affect insurance in some cases. Genetic counseling helps.