ADPKD Disease Overview

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease and one of the leading genetic causes of end-stage renal disease (ESRD). This page is the entry point of the knowledge base, helping you understand the disease as a whole: where it comes from, how it progresses, what symptoms it causes, how it is diagnosed and treated, and what you can do as a patient or family member. In-depth content for each topic is available on the corresponding sub-pages.

What is ADPKD

ADPKD is an autosomal dominant genetic disorder characterized by the growth of multiple cysts in both kidneys. Cysts may be absent or very small at birth, but they gradually increase in number and size with age, eventually compressing and destroying normal kidney tissue. This leads to progressive decline in kidney function, and some patients reach end-stage renal disease (ESRD), requiring dialysis or kidney transplantation.

• Full name: Autosomal Dominant Polycystic Kidney Disease
• Nature: The most common inherited kidney disease
• Global prevalence: Approximately 1:1,000 to 1:2,500 (Source: KDIGO 2025 ADPKD Guideline; Torres & Harris, Lancet 2014, PMID: 25393249)
• Core pathology: Multiple cysts develop bilaterally in the kidneys, growing progressively in number and size with age
• Possible outcome: Kidney function decline — not everyone reaches ESRD (see the Prognosis section below)

ADPKD is not an extremely rare disease — its prevalence is comparable to Down syndrome, but public awareness is low. Because symptoms often do not become apparent until middle age, many people carry the gene for decades before diagnosis.

Genetics

ADPKD is caused by mutations in the PKD1 or PKD2 gene and follows an autosomal dominant inheritance pattern. This means that if one parent is affected, each child — regardless of sex — has a 50% chance of inheriting the disease-causing gene; males and females are affected equally.

• PKD1 gene (~85% of cases): Located on chromosome 16 (16p13.3), encodes polycystin-1. PKD1 mutations are generally more severe, with earlier progression to ESRD (Source: Torres & Harris, Lancet 2014, PMID: 25393249).
• PKD2 gene (~15% of cases): Located on chromosome 4 (4q22.1), encodes polycystin-2. PKD2 mutations generally progress more slowly.
• De novo mutations (~10%): Approximately 10% of patients have no family history and carry a new (de novo) mutation, but can still pass it on to offspring with a 50% probability.

Polycystin-1 and polycystin-2 are key proteins on the primary cilia of kidney tubule cells, involved in cell signaling and fluid sensing. Their dysfunction leads to abnormal cell proliferation and fluid secretion, resulting in cyst formation.

Cyst Formation Mechanism

The formation and growth of cysts in ADPKD follows the second-hit hypothesis: a person inherits one mutated copy of PKD1 or PKD2 from a parent, but cysts only develop when a somatic "second hit" inactivates the remaining normal copy in an individual kidney tubule cell. That cell then proliferates abnormally and begins secreting fluid, forming a cyst.

• Polycystin dysfunction: Loss of functional polycystin-1 or polycystin-2 disrupts the primary cilium's ability to sense fluid flow and regulate cell proliferation, leading to uncontrolled cell growth and cyst expansion.
• cAMP signaling: Elevated intracellular cyclic AMP (cAMP) levels drive fluid secretion into the cyst lumen and promote cell proliferation. This pathway is the target of tolvaptan, the only approved disease-specific drug for ADPKD.
• Second-hit model: Cysts arise clonally from individual tubule cells that have sustained a second somatic mutation, explaining why cysts develop gradually and in increasing numbers over a lifetime.

Disease Progression

ADPKD is a chronically progressive disease, but individual variation is enormous. The Mayo Imaging Classification (based on height-adjusted total kidney volume and age) categorizes patients into classes 1A–1E to predict the rate of progression (Source: Irazabal MV et al., JASN 2015, PMID: 26133689).

Early stage (typically ages 20–40)

• Kidneys already have cysts, but kidney function (eGFR) is usually still within the normal range — eGFR may remain normal for decades
• Hypertension may appear — this is often the first sign, with approximately 50% of patients developing elevated blood pressure before age 30 (Source: KDIGO 2025 ADPKD Guideline)
• Flank or abdominal discomfort and microscopic hematuria may occur
• Total kidney volume (TKV) begins to increase — an important early indicator of disease progression rate

Middle stage (typically ages 40–60)

• Cysts increase in number and size; kidney volume becomes markedly enlarged (some patients can palpate an abdominal mass)
• Kidney function begins to decline; eGFR gradually decreases
• Hypertension worsens and requires more aggressive medication management
• Complications may arise: urinary tract infections, kidney stones, cyst bleeding, cyst infections

Late stage (typically after age 60, with large individual variation)

• Kidney function severely declines; some patients reach ESRD
• Kidney replacement therapy is needed: hemodialysis, peritoneal dialysis, or kidney transplantation
• Individual variation is large — not everyone reaches ESRD; most PKD2 mutation carriers never reach ESRD or only very late in life

Typical ESRD age

Genotype significantly influences the average age at which ESRD is reached (these are population averages; individual variation is large and requires medical assessment):

• PKD1 truncating mutations: Average ESRD at approximately age 55 (Source: Cornec-Le Gall et al., JASN 2016, PMID: 27217377)
• PKD1 non-truncating mutations: Average ESRD at approximately age 67
• PKD2 mutations: Average ESRD at approximately age 79

Beyond genotype, blood pressure control, body weight, sodium intake, hydration, and smoking status also significantly affect progression rate.

Common Symptoms

ADPKD symptoms vary by disease stage. In the early stage, patients may feel completely fine, and the disease is often discovered during a routine checkup or evaluation for hypertension. Common manifestations include:

• Hypertension: The most common early sign, appearing in approximately 50% of patients before age 30. Hypertension is both a symptom and a risk factor that accelerates kidney function decline, requiring active management (Source: KDIGO 2025 ADPKD Guideline)
• Flank or back pain: Often caused by cyst enlargement stretching the renal capsule, cyst bleeding, or infection; can range from dull ache to sudden severe pain
• Hematuria: Gross hematuria (visible blood in urine) or microscopic hematuria (detected only on lab testing), usually caused by cyst bleeding and often self-resolving
• Urinary tract infections (UTIs): Including cystitis and pyelonephritis; more common in women; cyst infections are more difficult to treat
• Kidney stones: Higher incidence than in the general population, often related to abnormal uric acid metabolism and altered urinary tract structure
• Nocturia: Increased nighttime urination due to reduced kidney concentrating ability; can appear early in the disease
• Fatigue: May be related to anemia (in late-stage kidney decline), reduced sleep quality, and psychological burden
• Abdominal enlargement