ADPKD Disease Overview

Autosomal dominant enfermedad renal poliquística (ADPKD) is the most common inherited enfermedad renal and one of the leading gentic causes of enfermedad renal en estadio terminal (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 síntomas it causes, how it is diagnosed and treated, and what you can do as a paciente or family member. In-depth content for each topic is available on the corresponding sub-pages.

What is ADPKD

ADPKD is an autosomal dominant gentic disorder characterized by the growth of multiple quistes in both riñóns. Cysts may be absent or very small at birth, but they gradually increase in number and size with age, eventually compressing and destroying normal riñón tejido. This leads to progresivo decline in función renal, and some pacientes reach enfermedad renal en estadio terminal (ESRD), requiring diálisis or trasplante renalation.

• Full name: Autosomal Dominant Polyquisteic Kidney Disease
• Nature: The most common inherited enfermedad renal
• Global prevalencia: Approximately 1:1,000 to 1:2,500 (Source: KDIGO 2025 ADPKD Guideline; Torres & Harris, Lancet 2014, PMID: 25393249)
• Core pathology: Multiple quistes develop bilaterally in the riñóns, growing progresivoly 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 prevalencia is comparable to Down syndrome, but public awareness is low. Because síntomas often do not become apparent until middle age, many people carry the gen for decades before diagnóstico.

Genetics

ADPKD is caused by mutacións in the PKD1 or PKD2 gen 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 gen; males and females are affected equally.

• PKD1 gen (~85% of cases): Located on chromosome 16 (16p13.3), encodes polyquistein-1. PKD1 mutacións are genrally more severe, with earlier progresión to ESRD (Source: Torres & Harris, Lancet 2014, PMID: 25393249).
• PKD2 gen (~15% of cases): Located on chromosome 4 (4q22.1), encodes polyquistein-2. PKD2 mutacións genrally progress more slowly.
• De novo mutacións (~10%): Approximately 10% of pacientes have no antecedentes familiares and carry a new (de novo) mutación, but can still pass it on to offspring with a 50% probability.

Polyquistein-1 and polyquistein-2 are key proteínas on the primary cilios of riñón túbulo células, involved in célula signaling and fluid sensing. Their dysfunction leads to abnormal célula proliferación and fluid secreción, resulting in formación de quistes.

Cyst Formation Mechanism

The formation and growth of quistes in ADPKD follows the second-hit hypothesis: a person inherits one mutated copy of PKD1 or PKD2 from a parent, but quistes only develop when a somatic "segundo impacto" inactivates the remaining normal copy in an individual riñón túbulo célula. That célula then proliferates abnormally and begins secreting fluid, forming a quiste.

• Polyquistein dysfunction: Loss of functional polyquistein-1 or polyquistein-2 disrupts the primary cilio's ability to sense fluid flow and regulate célula proliferación, leading to uncontrolled célula growth and quiste expansion.
• cAMP signaling: Elevated intracélulaular cyclic AMP (cAMP) levels drive fluid secreción into the quiste lumen and promote célula proliferación. This pathway is the target of tolvaptán, the only approved disease-specific drug for ADPKD.
• Second-hit model: Cysts arise clonally from individual túbulo células that have sustained a second somatic mutación, explaining why quistes develop gradually and in increasing numbers over a lifetime.

Disease Progression

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

Early estadio (typically ages 20–40)

• Kidneys already have quistes, but función renal (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 pacientes developing elevated presión arterial before age 30 (Source: KDIGO 2025 ADPKD Guideline)
• Flank or abdominal discomfort and microscopic hematuria may occur
• Total riñón volume (TKV) begins to increase — an important early indicator of disease progresión rate

Middle estadio (typically ages 40–60)

• Cysts increase in number and size; riñón volume becomes markedly enlarged (some pacientes can palpate an abdominal mass)
• Kidney function begins to decline; eGFR gradually decreases
• Hypertension worsens and requires more aggressive medicamento management
• Complications may arise: infección del tracto urinarios, cálculos renales, sangrado de quiste, infección de quistes

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

• Kidney function severely declines; some pacientes reach ESRD
• Kidney replacement therapy is needed: hemodiálisis, diálisis peritoneal, or trasplante renalation
• Individual variation is large — not everyone reaches ESRD; most PKD2 mutación 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 mutación truncantes: Average ESRD at approximately age 55 (Source: Cornec-Le Gall et al., JASN 2016, PMID: 27217377)
• PKD1 non-mutación truncantes: Average ESRD at approximately age 67
• PKD2 mutacións: Average ESRD at approximately age 79

Beyond genotype, presión arterial control, body weight, sodio intake, hydration, and tabaquismo status also significantly affect progresión rate.

Common Symptoms

ADPKD síntomas vary by disease estadio. In the early estadio, pacientes may feel completely fine, and the disease is often discovered during a routine checkup or evaluation for hipertensión. Common manifestations include:

• Hypertension: The most common early sign, appearing in approximately 50% of pacientes before age 30. Hypertension is both a síntoma and a riesgo factor that accelerates función renal decline, requiring active management (Source: KDIGO 2025 ADPKD Guideline)
• Flank or dolor de espalda: Often caused by quiste enlargement stretching the renal capsule, sangrado de quiste, or infection; can range from dull ache to sudden severe pain
• Hematuria: Gross hematuria (visible blood in orina) or microscopic hematuria (detected only on lab testing), usually caused by sangrado de quiste and often self-resolving
• Urinary tract infections (UTIs): Including quisteitis and pyelonephritis; more common in women; infección de quistes are more difficult to treat
• Kidney stones: Higher incidencia than in the genral population, often related to abnormal uric acid metabolism and altered urinario tract structure
• Nocturia: Increased nighttime urination due to reduced riñón concentrating ability; can appear early in the disease
• Fatigue: May be related to anemia (in late-estadio riñón decline), reduced sleep quality, and psychological burden
• Abdominal enlargement