Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Summary
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common inherited kidney disease, affecting 1 in 400-1000 people. It is caused by mutations in PKD1 (85%) or PKD2 (15%) genes, leading to progressive bilateral renal cyst development and eventual end-stage renal disease (ESRD). Beyond the kidneys, ADPKD is a systemic ciliopathy with extra-renal manifestations including liver cysts, intracranial aneurysms, and cardiac valve abnormalities. Management focuses on blood pressure control, slowing progression with tolvaptan in selected patients, and screening for complications.
Key Facts
- Prevalence: 1 in 400-1000 (most common hereditary kidney disease)
- Inheritance: Autosomal dominant (50% transmission to offspring)
- Genes: PKD1 (chromosome 16, 85%, more severe) or PKD2 (chromosome 4, 15%, milder)
- ESRD: 50% by age 60 (PKD1) or 70 (PKD2)
- Extra-renal: Liver cysts (80%), intracranial aneurysms (8-12%), MVP (25%)
- Key management: BP control less than 130/80; tolvaptan for rapidly progressive disease
Clinical Pearls
The Thunderclap Headache: Any patient with ADPKD presenting with sudden severe headache must be investigated for subarachnoid haemorrhage. Berry aneurysms occur in 8-12% of ADPKD patients and are the most feared complication.
Family Screening: Offspring have 50% risk of inheriting ADPKD. Offer screening by ultrasound from age 18-20 or earlier if symptomatic. Genetic testing available for at-risk individuals.
The Liver Connection: Liver cysts are present in 80% of ADPKD patients by age 60. They rarely cause liver failure but can cause mass effect, pain, and rarely infection.
Why This Matters Clinically
ADPKD is a leading cause of ESRD requiring dialysis or transplantation. Early diagnosis allows blood pressure optimisation, lifestyle modification, and identification of patients who may benefit from tolvaptan to slow progression. Recognition of extra-renal manifestations, particularly intracranial aneurysms, can prevent catastrophic complications.
Incidence & Prevalence
- Prevalence: 1 in 400 to 1 in 1000 live births
- Accounts for: 5-10% of all ESRD cases requiring RRT
- PKD1: 85% of cases; more severe, earlier ESRD
- PKD2: 15% of cases; milder, later ESRD
- De novo mutations: 5-10% (no family history)
Demographics
| Factor | Details |
|---|---|
| Age at diagnosis | Usually 30-50 years; earlier with family history |
| Sex | Equal male:female inheritance; males may progress faster |
| Ethnicity | All ethnic groups equally affected |
| Geography | Worldwide distribution |
Risk Factors
Non-Modifiable:
- Family history (autosomal dominant inheritance)
- PKD1 mutation (vs PKD2 — more severe)
- Male sex (slightly faster progression)
- Truncating mutation (vs non-truncating)
Modifiable:
| Risk Factor | Impact on Progression |
|---|---|
| Hypertension | Major driver of progression |
| Smoking | Accelerates decline |
| High protein diet | May accelerate cyst growth |
| Caffeine | Theoretical concern (cAMP pathway) |
Mechanism
Step 1: Genetic Mutation
- PKD1 (85%): Encodes polycystin-1 (PC1) — large transmembrane protein
- PKD2 (15%): Encodes polycystin-2 (PC2) — calcium channel
- PC1-PC2 complex localised to primary cilia of renal tubular cells
Step 2: Ciliary Dysfunction
- Defective PC1-PC2 complex disrupts intracellular calcium signalling
- Increased cyclic AMP (cAMP) in tubular cells
- cAMP drives cell proliferation and fluid secretion
Step 3: Cyst Formation
- Focal cysts develop from tubular epithelium
- Cysts progressively enlarge due to cell proliferation and fluid secretion
- Cyst expansion compresses and destroys surrounding parenchyma
Step 4: Progressive Renal Failure
- Total kidney volume (TKV) increases exponentially
- Cyst growth leads to inflammation, fibrosis, and nephron loss
- GFR declines as functional parenchyma is destroyed
- ESRD typically by age 50-70
Classification
| Type | Gene | Chromosome | Clinical Features |
|---|---|---|---|
| ADPKD1 | PKD1 | 16p13.3 | 85% of cases; earlier ESRD (mean age 54) |
| ADPKD2 | PKD2 | 4q21 | 15% of cases; later ESRD (mean age 74) |
| ARPKD | PKHD1 | 6p12 | Autosomal recessive; infantile onset; severe |
Anatomical Considerations
- Cysts arise from any nephron segment
- Bilateral involvement (unlike simple cysts)
- Kidneys become massively enlarged (up to 4kg each)
- Liver cysts common but rarely cause hepatic dysfunction
- Berry aneurysms at Circle of Willis arterial bifurcations
Symptoms
Typical Presentation:
Atypical Presentations:
Signs
Red Flags
[!CAUTION] Red Flags — Urgent assessment required if:
- Sudden severe headache — exclude SAH (CT head ± LP; urgent neurosurgery if confirmed)
- Fever with flank pain — infected cyst (requires IV antibiotics, may need drainage)
- Acute severe flank pain with haematuria — cyst haemorrhage or rupture
- Rapidly declining renal function — exclude obstruction, infection, malignancy
- Uncontrolled hypertension — accelerates progression
Structured Approach
General:
- Blood pressure (hypertension common)
- Signs of CKD (pallor, uraemic fetor, peripheral oedema)
- Assess hydration status
Abdominal Examination:
- Inspect: Visible abdominal distension (massive organomegaly)
- Palpate: Bilateral flank masses (enlarged kidneys); hepatomegaly
- Percuss: Dull flanks (organomegaly)
- Auscultate: Renal bruits (rare)
Cardiovascular:
- Heart sounds — murmur of mitral valve prolapse (25%)
- Peripheral pulses and oedema
Neurological:
- If any headache or neurological symptoms — detailed neuro exam
Special Tests
| Test | Technique | Positive Finding | Sensitivity/Specificity |
|---|---|---|---|
| Blood pressure | Standard measurement | Greater than 130/80 | N/A |
| Abdominal palpation | Bimanual palpation of flanks | Bilateral flank masses | Variable |
| Urinalysis | Dipstick | Haematuria, proteinuria | N/A |
First-Line (Bedside)
- Blood pressure — Essential for all patients
- Urinalysis — Haematuria, proteinuria, leukocytes (infection)
- Point-of-care glucose — Diabetes screen
Laboratory Tests
| Test | Expected Finding | Purpose |
|---|---|---|
| U&Es/Creatinine | May be elevated | Assess renal function (eGFR) |
| Urine ACR | May show albuminuria | Assess proteinuria |
| FBC | May show anaemia (CKD) | Baseline |
| LFTs | Usually normal despite liver cysts | Baseline |
| Urine culture | If infection suspected | Guide antibiotic therapy |
Imaging
| Modality | Findings | Indication |
|---|---|---|
| Ultrasound | Bilateral enlarged kidneys with multiple cysts | First-line; diagnosis and screening |
| MRI | Accurate TKV measurement; better cyst characterisation | Staging; tolvaptan eligibility |
| CT | Cyst complications (haemorrhage, infection) | Acute presentations |
| MRA Brain | Berry aneurysms | Screening in those with family history of SAH or prior to major surgery |
Diagnostic Criteria
Unified Ultrasound Criteria (Pei et al. 2009):
| Age | At-Risk Individual (Family History) |
|---|---|
| 15-39 | ≥3 cysts (unilateral or bilateral) |
| 40-59 | ≥2 cysts in each kidney |
| ≥60 | ≥4 cysts in each kidney |
Disease Exclusion:
- Fewer than 2 cysts in each kidney in at-risk individual greater than 40 years effectively excludes ADPKD
Genetic Testing:
- Indicated when imaging inconclusive, young individuals, or for family planning
Management Algorithm
ADPKD CONFIRMED
↓
┌─────────────────────────────────────────┐
│ BASELINE ASSESSMENT │
│ eGFR, BP, TKV (MRI), Family history │
└─────────────────────────────────────────┘
↓
┌─────────────────────────────────────────┐
│ BLOOD PRESSURE CONTROL │
│ Target less than 130/80 (all patients) │
│ ACEi/ARB first-line │
└─────────────────────────────────────────┘
↓
┌─────────────────────────────────────────┐
│ ASSESS PROGRESSION RISK │
├─────────────────────────────────────────┤
│ RAPID PROGRESSOR → Consider Tolvaptan │
│ (CKD 2-3, TKV >750ml, age <50) │
│ SLOW PROGRESSOR → Conservative │
└─────────────────────────────────────────┘
↓
┌─────────────────────────────────────────┐
│ COMPLICATION SCREENING │
│ MRA brain if family history SAH │
│ Monitor renal function 6-12 monthly │
└─────────────────────────────────────────┘
↓
┌─────────────────────────────────────────┐
│ ESRD MANAGEMENT │
│ Dialysis or Transplantation │
│ (Nephrectomy may be needed for space) │
└─────────────────────────────────────────┘
Acute/Emergency Management
Cyst Infection:
- Blood and urine cultures
- IV antibiotics (fluoroquinolones penetrate cysts best)
- CT or MRI to identify infected cyst
- Percutaneous drainage if no response to antibiotics
Cyst Haemorrhage:
- Usually conservative (bed rest, analgesia, fluids)
- Transfusion if significant blood loss
- Rarely requires embolisation
Subarachnoid Haemorrhage:
- Emergency CT head → if positive, urgent neurosurgery referral
- If CT negative but clinical suspicion high → lumbar puncture
- Neurosurgical intervention (coiling or clipping)
Conservative Management
- Adequate hydration (2.5-3L/day) — suppresses vasopressin
- Low sodium diet (less than 2g/day)
- Avoid nephrotoxins (NSAIDs, aminoglycosides)
- Smoking cessation
- Moderate protein intake
Medical Management
| Drug Class | Drug | Dose | Duration |
|---|---|---|---|
| ACE inhibitor | Ramipril | 5-10mg OD | Lifelong |
| ARB | Losartan | 50-100mg OD | Lifelong |
| Vasopressin antagonist | Tolvaptan | 45/15mg → 90/30mg | Long-term (TEMPO 3:4 eligible) |
| Statin | Atorvastatin | 20mg OD | If CVD risk elevated |
Tolvaptan Eligibility (NICE TA580):
- CKD stage 2-3 (eGFR 25-90)
- Evidence of rapidly progressive disease (TKV greater than 750ml, eGFR decline greater than 2.5ml/min/year)
- Requires monitoring of LFTs (hepatotoxicity risk)
Surgical Management (if applicable)
Indications:
- Recurrent cyst infections not responding to antibiotics
- Massive symptomatic hepatomegaly (liver cyst fenestration)
- Pre-transplant nephrectomy (if kidneys too large)
Procedures:
- Cyst aspiration and sclerotherapy (symptomatic simple cysts)
- Laparoscopic cyst decortication (recurrent symptomatic cysts)
- Nephrectomy (pre-transplant or for intractable symptoms)
- Renal transplantation (ESRD)
Disposition
- Admit if: Infected cyst, significant haemorrhage, SAH, acute renal deterioration
- Discharge if: Routine — managed in outpatient nephrology
- Follow-up: Annual renal function, BP review; MRI for TKV if on tolvaptan
Immediate (Acute Presentations)
| Complication | Incidence | Presentation | Management |
|---|---|---|---|
| Cyst haemorrhage | 50% lifetime | Acute flank pain, haematuria | Conservative, rarely embolisation |
| Cyst infection | 1-2% per year | Fever, flank pain, raised WCC/CRP | IV antibiotics ± drainage |
| SAH (aneurysm rupture) | 1-2% lifetime | Thunderclap headache, collapse | Emergency neurosurgery |
Early (Months-Years)
- Hypertension: Present in 60% by age 30 — aggressive control needed
- Renal calculi: 20-30% — manage as standard
- UTIs: Increased frequency — treat promptly
Late (Years-Decades)
- ESRD: 50% by age 60 (PKD1) — dialysis or transplant
- Massive organomegaly: Pain, early satiety, reduced QoL
- Liver cyst complications: Mass effect, infection (rare liver failure)
- Cardiac valve disease: MVP (25%), rarely requires intervention
Natural History
- Cyst number and size increase with age
- TKV doubles approximately every 3-5 years
- GFR typically stable until TKV greater than 1500ml, then declines
- ESRD: Mean age 54 (PKD1) or 74 (PKD2)
Outcomes with Treatment
| Variable | Outcome |
|---|---|
| Tolvaptan effect | 30% reduction in TKV growth; 25% slower eGFR decline |
| BP control effect | Slows progression; reduces CVD risk |
| Transplant outcomes | Equal or better than other causes of ESRD |
Prognostic Factors
Good Prognosis:
- PKD2 mutation (vs PKD1)
- Female sex
- Diagnosis at older age
- Smaller TKV
- Well-controlled blood pressure
Poor Prognosis:
- PKD1 truncating mutation
- Male sex
- Early diagnosis (larger cyst burden)
- Large TKV (greater than 1500ml)
- Uncontrolled hypertension
- Family history of early ESRD
Key Guidelines
- KDIGO Controversies Conference (2015) — ADPKD management consensus. Kidney International
- NICE TA580 (2019) — Tolvaptan for treating ADPKD. NICE TA580
- ERA-EDTA Working Group (2016) — ADPKD management recommendations.
Landmark Trials
TEMPO 3:4 Trial (2012) — Tolvaptan in ADPKD
- 1445 patients randomised to tolvaptan vs placebo
- Key finding: Tolvaptan reduced TKV growth by 50% and slowed eGFR decline
- Clinical Impact: Tolvaptan approved for rapidly progressive ADPKD
HALT-PKD Trials (2014) — Blood pressure targets in ADPKD
- 558 patients randomised to standard (120-130/70-80) vs low (95-110/60-75) BP targets
- Key finding: Lower BP target slowed TKV growth but no significant eGFR benefit
- Clinical Impact: Supports aggressive BP control, though optimal target debated
REPRISE Trial (2017) — Tolvaptan in later CKD stages
- 1370 patients with CKD 3b-4
- Key finding: Tolvaptan slowed eGFR decline in later-stage disease
- Clinical Impact: Expanded tolvaptan use to CKD 3b-4
Evidence Strength
| Intervention | Level | Key Evidence |
|---|---|---|
| Tolvaptan | 1b | TEMPO 3:4, REPRISE Trials |
| ACEi/ARB for BP control | 1b | HALT-PKD |
| MRA brain screening | 2b | Observational studies, expert consensus |
| Genetic testing | 2a | Diagnostic accuracy studies |
What is ADPKD?
ADPKD (Autosomal Dominant Polycystic Kidney Disease) is an inherited condition where many fluid-filled sacs (cysts) grow in your kidneys over time. Think of your kidneys like sponges — normally they have tiny tubes that filter your blood. In ADPKD, these tubes develop balloon-like cysts that slowly get bigger, eventually squeezing out the healthy kidney tissue.
Why does it matter?
As the cysts grow, they replace healthy kidney tissue. Over many years, this can lead to kidney failure, meaning your kidneys can no longer filter waste from your blood properly. ADPKD can also affect other parts of your body, including the liver (where cysts can also grow) and blood vessels in the brain (where weak spots called aneurysms can form).
How is it treated?
- Blood pressure control: Keeping your blood pressure low (below 130/80) is the most important thing to protect your kidneys.
- Healthy lifestyle: Drink plenty of water, reduce salt, don't smoke.
- Medication (tolvaptan): For some people with rapidly growing cysts, a medication called tolvaptan can slow cyst growth.
- Monitoring: Regular blood tests and scans to monitor kidney function.
- If kidneys fail: Dialysis or a kidney transplant can take over kidney function.
What to expect
- ADPKD is a lifelong condition that progresses slowly over decades
- Many people maintain good kidney function well into their 50s or 60s
- You will need regular check-ups with a kidney specialist
- Your children have a 50% chance of inheriting the condition — screening is available
When to seek help
Contact your doctor or go to A&E if you experience:
- Sudden severe headache (worst headache of your life) — this is an emergency
- Fever with back or side pain (possible infected cyst)
- Blood in your urine with severe pain
- Swelling of your legs or feeling very tired and unwell
Primary Guidelines
- Chapman AB, et al. Autosomal-dominant polycystic kidney disease (ADPKD): executive summary from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2015;88(1):17-27. PMID: 25786098
Key Trials
- Torres VE, et al. Tolvaptan in patients with autosomal dominant polycystic kidney disease (TEMPO 3:4). N Engl J Med. 2012;367(25):2407-18. PMID: 23121377
- Schrier RW, et al. Blood pressure in early autosomal dominant polycystic kidney disease (HALT-PKD). N Engl J Med. 2014;371(24):2255-66. PMID: 25399733
- Torres VE, et al. Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease (REPRISE). N Engl J Med. 2017;377(20):1930-1942. PMID: 29105594
Further Resources
- PKD Charity UK: pkdcharity.org.uk
- Kidney Research UK: kidneyresearchuk.org
- NHS ADPKD Information: nhs.uk/conditions/autosomal-dominant-polycystic-kidney-disease-adpkd
Last Reviewed: 2025-12-24 | MedVellum Editorial Team
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.