Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Summary
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the Most Common Inherited Cause of End-Stage Renal Disease (ESRD), affecting approximately 1 in 400-1000 individuals worldwide. It is caused by mutations in PKD1 (85%) or PKD2 (15%) genes encoding Polycystin-1 and Polycystin-2 respectively, which are involved in ciliary signalling, Cell proliferation, And fluid secretion. The hallmark is Progressive Development of Multiple Fluid-Filled Cysts in Both Kidneys, leading to massive renal enlargement, Destruction of normal parenchyma, And eventual Renal Failure. ESRD typically occurs by 55-60 years (PKD1) or 70-75 years (PKD2). ADPKD is a Systemic Disease with extrarenal manifestations including Hepatic Cysts (Most Common), Intracranial Aneurysms (5-10%), Cardiac Valve Abnormalities, And Colonic Diverticulae. Complications include Hypertension, Chronic Pain, Cyst Infection/Haemorrhage, Nephrolithiasis, And Subarachnoid Haemorrhage. Management focuses on Blood Pressure Control (ACEi/ARB), Hydration, And the vasopressin V2 receptor antagonist Tolvaptan which slows cyst growth and eGFR decline in selected patients. Renal replacement therapy (Dialysis or Transplantation) is required for ESRD. [1,2,3]
Key Facts
| Fact | Value |
|---|---|
| Definition | Autosomal dominant inherited cystic kidney disease |
| Prevalence | 1:400-1:1000 |
| Genes | PKD1 (85%), PKD2 (15%) |
| Inheritance | 50% risk to offspring |
| Mechanism | Two-hit hypothesis, cAMP-driven cyst growth |
| ESRD (PKD1) | ~55-60 years |
| ESRD (PKD2) | ~70-75 years |
| Most Common Extrarenal | Hepatic cysts (Greater than 80% by age 60) |
| Key Complication | Intracranial aneurysm (5-10%) |
| First-line BP Treatment | ACE inhibitor or ARB |
| Disease-Modifying | Tolvaptan (Selected patients) |
| Key Trial | TEMPO 3:4 (Tolvaptan reduces TKV growth by 49%) |
| BP Target | Less than 130/80 mmHg (Less than 110/75 in early disease) |
| Cyst Infection Antibiotics | Fluoroquinolones (Penetrate cysts) |
| Aneurysm Screen Modality | MRA (Non-invasive) |
| Tolvaptan Side Effect | Polyuria (Expected), Hepatotoxicity (Monitor LFTs) |
Clinical Pearls
"PKD1 = Earlier, More Severe; PKD2 = Later, Milder": PKD1 mutations cause earlier ESRD.
"Screen Family History of Subarachnoid Haemorrhage": Indicates need for intracranial aneurysm screening.
"Tolvaptan Slows Progression": V2R antagonist reduces cyst growth. Requires liver monitoring.
"Hydration is Key": Suppresses vasopressin and cyst growth.
"Cyst Infection Often Gram-Negative": Fluoroquinolones penetrate cysts well.
"Think of the Liver Too": Hepatic cysts present in Greater than 80% - Especially severe in women.
"Avoid NSAIDs": Nephrotoxic and can accelerate CKD progression.
"TKV Predicts Progression": Total Kidney Volume (MRI) is key for risk stratification (Mayo Classification).
"Mayo 1C-1E = Tolvaptan Candidates": Higher classes indicate rapid progressors who benefit from treatment.
"50% Inheritance Risk": Key for family counselling - Each child has 50% chance.
Why This Matters Clinically
ADPKD is the fourth leading cause of ESRD globally and accounts for 5-10% of all patients requiring renal replacement therapy. It affects multiple generations of families with significant psychological and socioeconomic impact. The availability of disease-modifying therapy (Tolvaptan) has changed management algorithms, Making early diagnosis and risk stratification crucial. Identification of patients at risk of intracranial aneurysm rupture is life-saving. ADPKD is frequently examined due to its genetic basis, Systemic manifestations, And evolving treatment options.
Global Burden
| Metric | Data | Notes |
|---|---|---|
| Prevalence | 1:400-1:1000 | Most common inherited kidney disease |
| Global Cases | ~12 million worldwide | Significant healthcare burden |
| ESRD Due to ADPKD | 5-10% of all ESRD | Fourth leading cause globally |
| New Mutations | ~10% | De novo mutations (No family history) |
| Penetrance | ~100% by age 40 | Will develop detectable cysts |
Incidence & Prevalence by Population
| Population | Prevalence | Notes |
|---|---|---|
| General Population | 1:400-1:1000 | Higher with modern imaging |
| ESRD Registries | 5-10% of dialysis patients | Major contributor to RRT burden |
| Autopsy Studies | 1:400 | Many undiagnosed cases |
| Clinical Diagnosis | 1:1000 | Lower due to asymptomatic cases |
Demographics
| Factor | Details | Clinical Significance |
|---|---|---|
| Inheritance | Autosomal Dominant | 50% risk to offspring |
| Sex | Equal prevalence | Males may progress faster |
| Ethnicity | All ethnic groups equally | No significant racial variation |
| Age at Diagnosis | Variable (20-50 years typical) | Often incidental finding |
| Age at ESRD | PKD1: 55-60 yrs; PKD2: 70-75 yrs | Gene-dependent |
Gene-Phenotype Correlation - Detailed
| Gene | Chromosome | Frequency | Protein | Age at ESRD | Features |
|---|---|---|---|---|---|
| PKD1 | 16p13.3 | 85% | Polycystin-1 | 55-60 years | More cysts, Larger kidneys, Earlier disease, More severe HTN |
| PKD2 | 4q21-22 | 15% | Polycystin-2 | 70-75 years | Fewer cysts, Milder disease, Later ESRD, Better prognosis |
| PKD1 Truncating | 16p13.3 | ~50% of PKD1 | Non-functional PC1 | ~55 years | Worst prognosis |
| PKD1 Non-truncating | 16p13.3 | ~50% of PKD1 | Partially functional PC1 | ~67 years | Intermediate prognosis |
Risk Factors for Rapid Progression
| Factor | Risk Level | Mechanism |
|---|---|---|
| PKD1 (Truncating Mutation) | High | Complete loss of PC1 function |
| Male Sex | Moderate | Hormonal factors |
| Early Hypertension (Less than 35 yrs) | High | Marker of severe cystic burden |
| Large TKV (Greater than 1500 mL) | High | Mayo 1C-1E classification |
| Early Symptoms (Less than 35 yrs) | High | Gross haematuria, Pain = Worse prognosis |
| Rapid TKV Growth (Greater than 5%/yr) | High | Fast progressors need intervention |
| Low eGFR at Diagnosis | High | Later stage at presentation |
Age-Related Milestones
| Age | Typical Findings |
|---|---|
| 0-20 years | Cysts may be detectable (Especially if gene-tested). Usually asymptomatic. |
| 20-40 years | Hypertension develops (60-80%). Cysts visible on imaging. TKV increasing. |
| 40-60 years | Symptoms common. TKV large. eGFR declining. Complications occur. |
| 60-70 years | ESRD (PKD1). RRT or transplant required. Some PKD2 still stable. |
| 70+ years | ESRD (PKD2). Most PKD1 already on RRT. |
Healthcare Burden
| Aspect | Impact |
|---|---|
| Hospital Admissions | Pain, Infections, Haemorrhage, Hypertensive emergencies |
| Dialysis Burden | 5-10% of dialysis population |
| Transplant Demand | Excellent candidates due to general health |
| Drug Costs | Tolvaptan is expensive but cost-effective in progressors |
| Family Impact | Genetic counselling, Screening of relatives |
Genetics
| Gene | Chromosome | Protein | Function |
|---|---|---|---|
| PKD1 | 16p13.3 | Polycystin-1 (PC1) | Transmembrane receptor, Mechanosensor |
| PKD2 | 4q21-22 | Polycystin-2 (PC2) | Calcium channel (TRPP2) |
Inheritance:
- Autosomal Dominant
- Each child of affected parent has 50% risk
- Variable expressivity within families
- ~10% de novo mutations
Molecular Mechanism:
- PC1 and PC2 form a receptor-channel complex
- Located in primary cilia, Plasma membrane, ER
- Sense fluid flow and regulate intracellular calcium
- Loss of function leads to dysregulated cell signalling
Pathophysiology
Step 1: "Two-Hit" Hypothesis
- First hit: Germline mutation (Inherited – All cells carry one mutant allele)
- Second hit: Somatic mutation in other allele (Random event in individual tubular cells)
- Explains focal cyst development (Only cells with both hits form cysts)
- Accounts for variable severity and asymmetric cyst distribution
Step 2: Cellular Changes in Cyst Formation
- Loss of functional polycystin → Decreased intracellular calcium
- Increased cAMP (Cyclic AMP) levels
- Activation of CFTR chloride channels → Fluid secretion into cyst lumen
- Increased Cell Proliferation (mTOR pathway activation)
- Increased Vasopressin V2 receptor signalling
Step 3: Cyst Growth
- Fluid accumulates in cyst lumen (Secretion)
- Cyst walls proliferate
- Cysts detach from tubules and enlarge autonomously
- Compression of adjacent parenchyma
- Gradual destruction of normal nephrons
Step 4: Progressive Kidney Enlargement
- Total Kidney Volume (TKV) increases exponentially
- Normal kidney ~150-200 mL → ADPKD can exceed 2-3 Litres
- TKV predicts rate of eGFR decline
- Kidneys palpable in advanced disease
Step 5: Renal Function Decline
- eGFR remains stable initially despite increasing TKV
- Once ~50% nephrons lost, eGFR declines
- Typical decline ~4-5 mL/min/year
- ESRD: PKD1 ~55-60 yrs, PKD2 ~70-75 yrs
Pathophysiology Diagram
Risk Prediction: Mayo Classification
| Class | TKV Growth Rate | Risk of ESRD |
|---|---|---|
| 1A | less than 1.5%/year | Low |
| 1B | 1.5-3%/year | Low-Moderate |
| 1C | 3-4.5%/year | Moderate |
| 1D | 4.5-6%/year | High |
| 1E | >6%/year | Very High |
Higher class = Candidate for Tolvaptan therapy
Key Principle
[!NOTE] ADPKD is often asymptomatic for decades. Many patients present with incidental imaging findings or through family screening. Hypertension is typically the first clinical sign, often preceding overt renal dysfunction by years.
Renal Manifestations - Detailed
Hypertension:
| Aspect | Details |
|---|---|
| Prevalence | 60-80% (Often before GFR decline) |
| Mechanism | RAAS activation, Cyst compression, Vascular stretching |
| Onset | Often before age 35 in PKD1 |
| Correlation | Correlates with TKV, Predicts progression |
| Target | Less than 130/80 mmHg (HALT-PKD) |
| Treatment | ACEi/ARB first-line |
Flank/Abdominal Pain:
| Type | Cause | Features | Management |
|---|---|---|---|
| Chronic Dull Pain | Kidney enlargement, Cyst stretching | Constant, Aching | Avoid NSAIDs. Paracetamol. Support. |
| Acute Severe Pain | Cyst haemorrhage or rupture | Sudden onset, Severe | Bed rest, Hydration, Analgesia |
| Colicky Pain | Nephrolithiasis | Radiating to groin | Stone management |
| Fever + Pain | Cyst infection | Localised, Fever, High WCC | Fluoroquinolones |
Gross Haematuria:
| Aspect | Details |
|---|---|
| Prevalence | 30-50% lifetime |
| Causes | Cyst rupture, Cyst haemorrhage, Stone, Infection |
| Duration | Usually self-limiting (2-7 days) |
| Management | Conservative, Hydration, Avoid NSAIDs, Rarely interventional |
| Red Flag | Prolonged haematuria, Clots, Obstruction |
Nephrolithiasis:
| Aspect | Details |
|---|---|
| Prevalence | 20-30% |
| Stone Types | Uric acid (Most common), Calcium oxalate |
| Risk Factors | Low urine pH, Low citrate, Urinary stasis |
| Management | Hydration, Citrate supplementation, Urological intervention if needed |
Cyst Infection:
| Aspect | Details |
|---|---|
| Prevalence | 30-50% lifetime |
| Organisms | Gram-negative (E. coli most common) |
| Diagnosis | Fever, Flank pain, Raised CRP, PET-CT if localisation needed |
| Treatment | Fluoroquinolones (Penetrate cysts), 4-6 weeks duration |
| If No Response | CT-guided drainage |
Renal Manifestations Summary Table
| Feature | Frequency | Details |
|---|---|---|
| Hypertension | 60-80% (Early) | Often first sign. Correlates with TKV. |
| Flank/Abdominal Pain | 60% | Cyst enlargement, Haemorrhage, Infection, Stones |
| Palpable Kidneys | Variable | Advanced disease - Ballotable masses |
| Gross Haematuria | 30-50% | Cyst rupture or haemorrhage |
| Nephrolithiasis | 20-30% | Uric acid or calcium oxalate stones |
| Cyst Infection | 30-50% lifetime | Gram-negative, Pain, Fever |
| Proteinuria | Mild (Usually less than 1g/day) | Not nephrotic range |
| Reduced eGFR/ESRD | Eventual | PKD1 earlier than PKD2 |
Extrarenal Manifestations - Detailed
Hepatic Cysts (Polycystic Liver Disease - PLD):
| Aspect | Details |
|---|---|
| Prevalence | Greater than 80% by age 60 |
| Risk Factors for Severe PLD | Female sex, Multiple pregnancies, Oestrogen exposure |
| Symptoms | Usually asymptomatic. Massive PLD: Abdominal distension, Early satiety, Dyspnoea |
| Complications | Rarely: Portal hypertension, Ascites, Cyst infection |
| Management | Avoid oestrogens, Somatostatin analogues (Lanreotide), Liver resection/Transplant |
Intracranial Aneurysms:
| Aspect | Details |
|---|---|
| Prevalence | 5-10% (General ADPKD), 20% (Family history of SAH) |
| Location | Circle of Willis (MCA, AComA, PComA) |
| Risk of Rupture | ~1% overall, Higher with FH, Larger aneurysms |
| Presentation of Rupture | "Worst headache of life", Sudden onset, Meningism, Collapse |
| Screening Indications | FH of SAH/Aneurysm, High-risk occupation, Pre-major surgery, Symptoms |
| Screening Modality | MRA (Non-invasive) |
| Management if Found | Neurosurgical opinion, Consider coiling/Clipping if greater than 5-7mm |
Cardiac Manifestations:
| Feature | Frequency | Notes |
|---|---|---|
| Mitral Valve Prolapse | 25% | Usually asymptomatic |
| Aortic Root Dilatation | Variable | Monitor in severe cases |
| LVH | Common | Due to hypertension |
Other Extrarenal Features:
| Feature | Frequency | Clinical Significance |
|---|---|---|
| Colonic Diverticulae | Increased risk | Especially if on dialysis - Higher complication rate |
| Abdominal/Inguinal Hernia | Increased | Due to increased abdominal pressure from enlarged kidneys |
| Seminal Vesicle Cysts | Common (Male) | Usually asymptomatic, May cause infertility rarely |
| Pancreatic Cysts | 5-10% | Rarely symptomatic, Not associated with pancreatitis |
| Arachnoid Cysts | Rare | Usually incidental |
Red Flags
[!CAUTION] Red Flags – Immediate Action Required:
- Sudden severe headache ("Worst headache of life") → Subarachnoid haemorrhage - Call 999/Emergency CT
- Fever + Flank pain + Raised inflammatory markers → Cyst infection - Antibiotics + Consider imaging
- Severe flank pain + Haematuria → Cyst haemorrhage/Rupture - Supportive care
- Gross haematuria with clots → Cyst bleed, Stone, or rarely malignancy
- Severe hypertension (Greater than 180/110) → Aggressive BP control
- Sudden onset abdominal pain with hypotension → Ruptured cyst/Internal bleeding
Symptom Progression by Age
| Age | Typical Features | Management Focus |
|---|---|---|
| 0-20 years | Often asymptomatic. Cysts may be detected on screening or incidentally. | Genetic counselling, Baseline imaging |
| 20-40 years | Hypertension develops (60-80%). Occasional flank pain. Cysts visible on imaging. TKV increasing. | BP control, Tolvaptan if eligible, Lifestyle |
| 40-60 years | Progressive symptoms. TKV large. eGFR declining. Complications (Pain, Infections, Haematuria). | Intensive management, Complication prevention, RRT planning |
| 60+ years | ESRD (PKD1). RRT required. PKD2 may still have preserved function. | Dialysis/Transplant, Symptom management |
Key Principle
[!NOTE] ADPKD examination is often unremarkable in early disease. Key findings become apparent as disease progresses. Always check blood pressure as this is often the first detectable abnormality.
Structured Approach for OSCE/Clinical
Introduction and Consent:
- Introduce yourself, Explain examination, Obtain consent
- Position patient supine at 45°, Adequately exposed (Abdomen visible)
General Inspection:
| Finding | Significance |
|---|---|
| Well-appearing | Common in early-moderate disease |
| Pallor | Anaemia of CKD |
| Uraemic Fetor | Bad breath - Advanced CKD/ESRD |
| Uraemic Frost | Rarely seen - Very advanced uraemia |
| Scratch Marks | Pruritus of CKD |
| Bruising | Uraemic coagulopathy |
| Muscle Wasting | Catabolic state of CKD |
| Fluid Overload | Peripheral oedema, Raised JVP |
Hands:
| Finding | Significance |
|---|---|
| Pallor of creases | Anaemia |
| Brown discolouration | Uraemic pigmentation |
| Lindsay's Nails (Half-and-Half) | CKD marker |
| Asterixis (Flapping Tremor) | Uraemic encephalopathy (Advanced) |
Cardiovascular:
| Component | Finding | Significance |
|---|---|---|
| Blood Pressure | Usually elevated | Often first sign |
| Pulse | Often bounding (If fluid overloaded) | |
| Heart Sounds | Murmurs (MVP in 25%) | Click-murmur of MVP |
| JVP | May be elevated | Fluid overload |
Abdominal Examination - Detailed:
| Step | Technique | Finding in ADPKD |
|---|---|---|
| Inspection | Look for distension | Enlarged kidneys/Liver may cause visible distension |
| Palpation (Superficial) | Light palpation | May feel masses if kidneys very large |
| Palpation (Deep) | Bimanual technique for kidneys | Ballotable bilateral renal masses |
| Liver | Start from RIF | Hepatomegaly if polycystic liver |
| Percussion | Resonant in flanks | Kidneys displace bowel |
| Auscultation | Renal artery bruits | Rare in ADPKD |
Kidney Palpation Technique:
| Step | Action |
|---|---|
| 1 | Place left hand behind patient's flank |
| 2 | Place right hand anteriorly below costal margin |
| 3 | Ask patient to take deep breath |
| 4 | Feel kidney descend between hands (Bimanual palpation) |
| 5 | Assess size, Surface (Nodular in ADPKD), Tenderness |
Key Examination Findings:
| Finding | Significance | Stage |
|---|---|---|
| Bilateral ballotable renal masses | Pathognomonic of ADPKD | Advanced |
| Irregular/Nodular kidney surface | Cysts creating bumpy contour | Moderate-Advanced |
| Hepatomegaly (Nodular) | Polycystic liver disease | Variable |
| Umbilical hernia | Increased abdominal pressure | Common |
| Inguinal hernia | Increased abdominal pressure | Common |
| Signs of portal hypertension | Massive PLD | Rare |
Signs of CKD to Look For:
| Sign | Indicates |
|---|---|
| Pallor | Anaemia |
| Uraemic tinge (Yellow-brown) | Uraemic pigmentation |
| Scratch marks | Uraemic pruritus |
| Pericardial rub | Uraemic pericarditis (Late) |
| Peripheral oedema | Fluid overload |
| Raised JVP | Fluid overload |
| Pulmonary crackles | Pulmonary oedema |
Documentation Checklist
| Component | Record |
|---|---|
| Blood Pressure | Essential - Record accurately |
| Kidney Size | If palpable - Estimate cm below costal margin |
| Liver Size | If palpable |
| Hernias | Umbilical, Inguinal |
| Fluid Status | Dehydrated, Euvolemic, Overloaded |
| Signs of CKD | Present/Absent |
What to Present in Viva/OSCE
"On examination, This patient appears well. Blood pressure is elevated at [X/Y]. On abdominal examination, There are bilateral ballotable renal masses with an irregular surface, Consistent with polycystic kidneys. There is also hepatomegaly. I note an umbilical hernia. There are no signs of advanced CKD. The findings are consistent with ADPKD."
Key Principle
[!NOTE] In ADPKD, investigations serve to: > 1. Confirm diagnosis (Imaging + Family history) > 2. Assess progression (TKV, eGFR) > 3. Identify complications > 4. Determine treatment eligibility (Tolvaptan)
Diagnostic Imaging
Ultrasound (First-Line):
| Age | Diagnostic Criteria (Unified Ravine Criteria for At-Risk Individuals) |
|---|---|
| 15-39 years | ≥3 cysts (Unilateral or bilateral) |
| 40-59 years | ≥2 cysts in each kidney |
| ≥60 years | ≥4 cysts in each kidney |
Sensitivity increases with age. May miss early disease in young at-risk individuals.
Ultrasound Findings:
| Finding | Description | Significance |
|---|---|---|
| Multiple Cysts | Bilateral, Variable size | Diagnostic |
| Enlarged Kidneys | Greater than 12cm, May be massive | Disease progression |
| Irregular Contour | Cysts create bumpy outline | Advanced disease |
| Liver Cysts | Often seen concomitantly | PLD |
| Echogenic Foci | May represent haemorrhage or stone | Complication |
MRI:
| Indication | Details |
|---|---|
| TKV Measurement | Gold standard for Total Kidney Volume |
| Risk Stratification | Mayo Classification (Height-adjusted TKV) |
| Tolvaptan Eligibility | Required for NICE criteria |
| Research | More accurate volume assessment |
MRI Mayo Classification:
| Class | TKV Characteristics | Risk |
|---|---|---|
| 1A | Less than 600 mL/m at 40 yrs | Low |
| 1B | 600-1200 mL/m | Low-Moderate |
| 1C | 1200-2000 mL/m | Moderate |
| 1D | 2000-3000 mL/m | High |
| 1E | Greater than 3000 mL/m | Very High |
CT Scan:
| Indication | Notes |
|---|---|
| Nephrolithiasis | Stone detection |
| Cyst Complication | Haemorrhage, Infection, Rupture |
| Pre-Transplant | Anatomy assessment |
| Contrast | Avoid if possible (CKD). Use for specific indications only. |
Laboratory Investigations
Routine Monitoring:
| Test | Frequency | Findings | Notes |
|---|---|---|---|
| eGFR/Creatinine | 6-12 monthly | Declining over time | Key prognostic marker |
| Urinalysis | 6-12 monthly | Haematuria, Mild proteinuria | Microscopic haematuria common |
| FBC | 6-12 monthly | Polycythaemia (Early), Anaemia (CKD) | EPO production |
| U&Es | 6-12 monthly | Electrolyte disturbance in CKD | |
| LFTs | If on Tolvaptan | Monitor for hepatotoxicity | Monthly for 18 months |
| Lipids | Annually | CVD risk | Associated with CKD |
| Glucose/HbA1c | Annually | Diabetes screening | CVD risk |
Investigations for Complications:
| Indication | Investigation |
|---|---|
| Cyst Infection Suspected | Urine culture, Blood cultures, CRP, CT (For localisation), Consider PET-CT |
| Cyst Haemorrhage | eHaemoglobin, CT (If persistent) |
| Nephrolithiasis | CT KUB (Non-contrast), Urine metabolic screen |
| SAH Suspected | Urgent CT Head (Non-contrast), LP if CT negative |
Genetic Testing
Indications:
| Scenario | Role of Genetic Testing |
|---|---|
| Diagnostic Uncertainty | Atypical imaging, Young patient, No family history |
| Family Planning | PGD (Pre-implantation genetic diagnosis), Prenatal testing |
| Living Donor Evaluation | Exclude ADPKD in potential related donor |
| Prognosis | PKD1 (Worse) vs PKD2 (Better), Truncating vs Non-truncating |
| Clinical Trials | May be required for enrolment |
What Genetic Testing Provides:
| Information | Clinical Use |
|---|---|
| PKD1 vs PKD2 | PKD1 = Earlier ESRD (55-60 vs 70-75) |
| Mutation Type | Truncating = Worse prognosis |
| Confirms Diagnosis | If imaging equivocal |
| Family Counselling | Enables predictive testing in relatives |
Screening for Complications
| Complication | Who to Screen | Modality | Frequency |
|---|---|---|---|
| Intracranial Aneurysm | FH of SAH/Aneurysm, High-risk job, Pre-surgery, Symptoms | MRA | Every 5 years if negative, 6-12 monthly if found |
| Hepatic Cysts | Symptomatic patients, Pre-pregnancy | Ultrasound/MRI | As needed |
| Cardiac Valve Disease | Murmur on examination | Echocardiogram | As needed |
| Aortic Root Dilatation | If concern | Echocardiogram | As needed |
Investigations Summary by Stage
| Stage | Key Investigations |
|---|---|
| Diagnosis | Ultrasound (Ravine criteria), Family history |
| Baseline Assessment | eGFR, TKV (MRI if considering Tolvaptan) |
| Monitoring Progression | eGFR 6-12 monthly, Repeat TKV if on Tolvaptan |
| Complication Workup | As indicated (Infection, Haemorrhage, Stones) |
| Aneurysm Screening | MRA in high-risk patients |
Management Algorithm
Key Principle
[!IMPORTANT] ADPKD is a SYSTEMIC disease requiring LIFELONG management:
- Blood pressure control is the cornerstone
- Disease-modifying therapy (Tolvaptan) for rapid progressors
- Complication management
- Family screening and genetic counselling
- Renal replacement therapy planning
Blood Pressure Control - Detailed
Evidence Base:
- HALT-PKD Trial showed rigorous BP control (Less than 110/75) slowed TKV growth in CKD 1-2
Target:
| Population | BP Target |
|---|---|
| CKD 1-2, Age 18-49 | Less than 110/75 mmHg (If tolerated, HALT-PKD) |
| All Others | Less than 130/80 mmHg |
| Elderly/CKD 4-5 | Less than 140/90 (Avoid hypotension) |
First-Line Agents:
| Agent | Dose | Notes |
|---|---|---|
| ACE Inhibitor (Ramipril, Lisinopril, Perindopril) | Titrate to max tolerated | First-line. RAAS inhibition. Reduces LVH. |
| ARB (Losartan, Candesartan, Irbesartan) | Titrate to max tolerated | If ACEi intolerant. Same benefits. |
Add-On Agents (If ACEi/ARB Not Sufficient):
| Agent | Preference | Notes |
|---|---|---|
| Calcium Channel Blocker (Amlodipine) | Second-line | Good efficacy |
| Thiazide Diuretic | Consider | Avoid if CKD 4-5 (Less effective) |
| Beta-Blocker | If tachycardia/Angina | Cardioprotective |
| Alpha-Blocker | Rarely | If resistant HTN |
AVOID:
- ❌ Dual ACEi + ARB (HALT-PKD showed no benefit and more side effects)
Disease-Modifying Therapy: Tolvaptan - Detailed Protocol
Mechanism: Vasopressin V2 receptor antagonist → Reduces cAMP in cyst epithelium → Slows cyst proliferation and fluid secretion → Slows TKV growth → Slows eGFR decline
Key Trials:
| Trial | Population | Key Finding |
|---|---|---|
| TEMPO 3:4 (2012) | n=1445, CKD 1-3 | Tolvaptan reduced TKV growth by 49%, eGFR decline by 26% over 3 years |
| REPRISE (2017) | n=1370, CKD 3-4 | Benefit extended to later stage CKD (eGFR 25-65) |
NICE TA873 (2023) Indications for Tolvaptan:
| Criterion | Requirement |
|---|---|
| Diagnosis | Confirmed ADPKD |
| CKD Stage | CKD Stage 2 (eGFR 60-89) or CKD Stage 3 (eGFR 30-59) |
| Rapid Progression | Evidence of rapidly progressive disease (Mayo 1C-1E, TKV greater than 750 mL) |
| Hanatotoxicity Risk | Acceptable (No liver disease) |
Dosing Schedule:
| Week | Morning Dose | Afternoon Dose | Total |
|---|---|---|---|
| 1-4 | 45 mg | 15 mg | 60 mg |
| 4-8 | 60 mg | 30 mg | 90 mg |
| 8+ | 90 mg | 30 mg | 120 mg |
Split dosing reduces nocturnal polyuria
Monitoring Protocol:
| Parameter | Frequency | Action if Abnormal |
|---|---|---|
| LFTs (ALT/AST/Bilirubin) | Monthly for 18 months, Then 3-monthly | Stop if ALT greater than 3x ULN or Bilirubin elevated |
| Sodium | Monthly initially | If Greater than 150, Increase water intake |
| Serum Osmolality | If symptomatic | Adjust hydration |
| Body Weight | Each visit | Assess hydration |
| Symptoms | Each visit | Polyuria, Nocturia, Thirst |
Side Effects and Management:
| Side Effect | Incidence | Management |
|---|---|---|
| Polyuria | Very common (Expected) | Warn patient. Adequate hydration. |
| Thirst | Very common | Drink to thirst (3-4 L/day) |
| Nocturia | Common | Take second dose early afternoon |
| Hypernatraemia | Uncommon | Increase water intake |
| Hepatotoxicity | 1-2% | Stop drug immediately. Liver recovers. |
Contraindications:
| Category | Examples |
|---|---|
| Absolute | Liver disease, Inability to perceive thirst, Unable to drink, Volume depletion |
| Relative | Non-adherence, Pregnancy, Breastfeeding |
Lifestyle and Conservative Management
| Intervention | Details | Evidence |
|---|---|---|
| Hydration | 3-4 L/day | Suppresses vasopressin. Reduces cAMP. |
| Salt Restriction | Less than 6g/day | Reduces BP, Fluid retention |
| Avoid Caffeine | Limit intake | May increase cyst growth (Weaker evidence) |
| Smoking Cessation | Essential | Major CVD risk factor |
| Weight Management | BMI 18.5-25 | Reduces metabolic burden |
| Moderate Protein | 0.8-1g/kg/day | Standard for CKD |
| Potassium-Rich Diet | If eGFR adequate | Cardioprotective |
| Avoid NSAIDs | Essential | Nephrotoxic, Reduce eGFR |
Management of Complications - Detailed
Cyst Pain Management:
| Treatment | When to Use | Notes |
|---|---|---|
| Paracetamol | First-line | Safe in CKD |
| Weak Opioids | If severe | Short-term. Monitor constipation. |
| Cyst Aspiration/Sclerotherapy | Large symptomatic cyst | Provides temporary relief |
| Laparoscopic Cyst Deroofing | Multiple large cysts | Surgical option |
| Nephrectomy | Severe pain, Pre-transplant | Last resort |
Cyst Infection Protocol:
| Step | Action |
|---|---|
| 1. Diagnose | Fever, Flank pain, Raised CRP. Blood/Urine cultures. Consider PET-CT if localisation unclear. |
| 2. Antibiotics | Fluoroquinolones (Ciprofloxacin 500mg BD). TMP-SMX alternative. Duration: 4-6 weeks. |
| 3. If No Response | CT-guided aspiration and drainage. Rarely surgery. |
Cyst Haemorrhage:
| Severity | Management |
|---|---|
| Mild | Bed rest, Hydration, Analgesia, Avoid anticoagulants |
| Severe/Prolonged | CT angiography. Rarely embolisation. |
Nephrolithiasis:
| Step | Action |
|---|---|
| Prevention | Hydration, Citrate supplementation (Potassium citrate) |
| Treatment | Urological referral. ESWL/Ureteroscopy. Avoid contrast if CKD. |
Polycystic Liver Disease:
| Severity | Management |
|---|---|
| Asymptomatic | Observation. Avoid oestrogens. |
| Symptomatic (Early Satiety, Distension) | Somatostatin analogues (Lanreotide/Octreotide) |
| Massive PLD | Liver resection/Transplant |
Renal Replacement Therapy
| Modality | Consideration | Notes |
|---|---|---|
| Haemodialysis | Standard. May need bilateral nephrectomy for space/Comfort. | Creates AV fistula early (eGFR less than 20) |
| Peritoneal Dialysis | Possible but limited by large kidneys/Hernias | Increased hernia risk |
| Transplantation | Excellent outcomes. Best option. | May need native nephrectomy (Size/Infection). Pre-emptive transplant ideal. |
Intracranial Aneurysm Screening
| Who to Screen | Modality | Follow-Up |
|---|---|---|
| Family history of SAH/Aneurysm | MRA | Repeat every 5 years if negative, 6-12 monthly if found |
| High-risk occupation (Pilot, Surgeon) | MRA | As above |
| Pre-major surgery (Esp. Cardiac) | MRA | If found, Neurosurgical opinion |
| Symptoms (Headache, Neuro signs) | Urgent MRA | Immediate referral if aneurysm |
| Patient request (Anxiety) | Consider MRA | Discuss pros/Cons |
Overview
| Category | Key Complications |
|---|---|
| Renal | Hypertension, Pain, Cyst infection, Cyst haemorrhage, Stones, CKD/ESRD |
| Hepatic | Polycystic liver disease (PLD), Massive hepatomegaly |
| Neurological | Intracranial aneurysm, Subarachnoid haemorrhage |
| Cardiac | Valve disease (MVP), LVH, Aortic root dilatation |
| Gastrointestinal | Colonic diverticula, Hernias |
Renal Complications - Detailed
Hypertension:
| Aspect | Details |
|---|---|
| Prevalence | 60-80% (Often before GFR decline) |
| Mechanism | RAAS activation, Cyst compression, Intrarenal ischaemia |
| Significance | Accelerates CKD progression, CVD risk |
| Target | Less than 130/80 (Consider less than 110/75 in young) |
| Treatment | ACEi/ARB first-line |
| Prevention | Early diagnosis and treatment |
Cyst Pain:
| Type | Cause | Management |
|---|---|---|
| Chronic Dull | Kidney enlargement | Paracetamol, Avoid NSAIDs |
| Acute Severe | Haemorrhage/Rupture | Bed rest, Analgesia, Conservative |
| Colicky | Nephrolithiasis | Stone management |
| Infective | Cyst infection | Fluoroquinolones |
| Refractory | Persistent | Cyst aspiration, Deroofing, Nephrectomy |
Cyst Infection:
| Aspect | Details |
|---|---|
| Prevalence | 30-50% lifetime |
| Organisms | Gram-negative (E. coli) |
| Diagnosis | Fever, Flank pain, Raised CRP. PET-CT if localisation unclear. |
| Treatment | Fluoroquinolones 4-6 weeks (Penetrate cysts) |
| If Refractory | CT-guided drainage |
| Prevention | Prompt UTI treatment, Good hydration |
Cyst Haemorrhage:
| Aspect | Details |
|---|---|
| Prevalence | 30-50% lifetime |
| Cause | Cyst rupture, Trauma |
| Presentation | Sudden flank pain, Gross haematuria |
| Management | Conservative (Bed rest, Hydration, Analgesia) |
| Duration | Usually self-limiting (2-7 days) |
| Severe Cases | Rarely embolisation |
Nephrolithiasis:
| Aspect | Details |
|---|---|
| Prevalence | 20-30% |
| Stone Types | Uric acid (Most common), Calcium oxalate |
| Risk Factors | Urinary stasis, Low pH, Low citrate |
| Prevention | Hydration, Citrate supplementation |
| Treatment | Urological (ESWL, Ureteroscopy) |
CKD and ESRD:
| Aspect | Details |
|---|---|
| Prevalence | Greater than 50% will develop ESRD |
| Timing | PKD1: 55-60 yrs, PKD2: 70-75 yrs |
| Management | Standard CKD care, RRT planning, Transplant listing |
Extrarenal Complications - Detailed
Polycystic Liver Disease (PLD):
| Aspect | Details |
|---|---|
| Prevalence | Greater than 80% by age 60 |
| Risk Factors | Female, Multiple pregnancies, Oestrogen |
| Usually | Asymptomatic |
| Severe Cases | Massive hepatomegaly, Early satiety, Dyspnoea |
| Treatment | Avoid oestrogens, Somatostatin analogues, Liver resection/Transplant |
Intracranial Aneurysms:
| Aspect | Details |
|---|---|
| Prevalence | 5-10% (20% if FH of SAH) |
| Location | Circle of Willis |
| Risk of Rupture | ~1% (Higher if large, FH) |
| Screening | MRA in high-risk (FH, Symptoms, Pre-surgery) |
| Management | Neurosurgical (Coiling/Clipping if greater than 5-7mm) |
Cardiac Complications:
| Complication | Prevalence | Management |
|---|---|---|
| Mitral Valve Prolapse | 25% | Usually asymptomatic, Echo monitoring |
| LVH | Common (HTN) | BP control |
| Aortic Root Dilatation | Variable | Echo monitoring if concern |
Gastrointestinal Complications:
| Complication | Details | Management |
|---|---|---|
| Colonic Diverticula | Increased risk (Especially on dialysis) | Fibre diet, Standard diverticulitis care |
| Hernias | Umbilical, Inguinal (Increased abdominal pressure) | Surgical repair |
Complications Summary Table
| Complication | Incidence | Management |
|---|---|---|
| Hypertension | 60-80% | ACEi/ARB, Lifestyle |
| Cyst Infection | 30-50% | Fluoroquinolones 4-6 weeks |
| Cyst Haemorrhage | 30-50% | Conservative |
| Nephrolithiasis | 20-30% | Hydration, Citrate, Urology |
| CKD/ESRD | Greater than 50% | RRT |
| Intracranial Aneurysm | 5-10% | Screening, Neurosurgery |
| PLD | Greater than 80% | Avoid oestrogens, Somatostatin if severe |
| MVP | 25% | Echo if symptomatic |
| Hernias | Increased | Surgical repair |
Progression to ESRD
| Gene | Median Age to ESRD | Notes |
|---|---|---|
| PKD1 | 55-60 years | Earlier, More severe |
| PKD2 | 70-75 years | Later, Milder |
Predictors of Rapid Progression
| Factor | Notes |
|---|---|
| PKD1 (Truncating Mutation) | Worst prognosis |
| Male Sex | Worse than female |
| Early Hypertension (less than 35 yrs) | Marker of severity |
| Large TKV | Mayo 1C-1E |
| Early Symptoms | Gross haematuria, Pain before 35 |
| Rapid TKV Growth | >5%/year |
Prognosis After RRT
| Modality | Notes |
|---|---|
| Transplantation | Excellent. Better outcomes than dialysis. Similar to other causes. |
| Dialysis | Survival comparable to other CKD aetiologies |
Key Guidelines
| Guideline | Organisation | Year | Key Recommendations |
|---|---|---|---|
| KDIGO ADPKD Guideline | KDIGO | 2015 | Diagnosis, BP targets, Management |
| ERA-EDTA/EKA ADPKD Guideline | European Renal Association | 2022 | Tolvaptan use, Risk stratification |
| NICE TA873 Tolvaptan | NICE | 2023 | Criteria for Tolvaptan in NHS |
| ACR Appropriateness Criteria | ACR | 2020 | Imaging in renal cystic disease |
Landmark Trials - Detailed
HALT-PKD Trial (2014)
| Aspect | Details |
|---|---|
| Design | RCT, n=558, Early ADPKD (eGFR Greater than 60) |
| Intervention | Standard BP (120-130/70-80) vs Rigorous (95-110/60-75); ACEi vs ACEi+ARB |
| Primary Outcome | TKV change |
| Result | Rigorous BP slowed TKV growth (5.6% vs 6.6%/yr). No benefit of dual blockade. |
| Clinical Impact | Supports lower BP target in early ADPKD |
| PMID | 25399733 |
TEMPO 3:4 Trial (2012)
| Aspect | Details |
|---|---|
| Design | RCT, n=1445, ADPKD with eGFR Greater than 60 |
| Intervention | Tolvaptan vs Placebo |
| Primary Outcome | TKV change |
| Result | Tolvaptan reduced TKV growth by 49% (2.8% vs 5.5%/yr) and eGFR decline by 26% |
| Clinical Impact | Established Tolvaptan as disease-modifying therapy |
| PMID | 23121377 |
REPRISE Trial (2017)
| Aspect | Details |
|---|---|
| Design | RCT, n=1370, ADPKD with CKD 3-4 (eGFR 25-65) |
| Intervention | Tolvaptan vs Placebo |
| Primary Outcome | eGFR slope |
| Result | Tolvaptan slowed eGFR decline by 1.27 mL/min/1.73m²/yr |
| Clinical Impact | Extended benefit to later CKD stages |
| PMID | 29105594 |
Evidence Strength Summary
| Intervention | Level | Evidence Source |
|---|---|---|
| ACEi/ARB for HTN | 1A | HALT-PKD, Multiple RCTs |
| Rigorous BP Control (Less than 110/75) | 1B | HALT-PKD |
| Tolvaptan (CKD 2-3) | 1A | TEMPO 3:4 |
| Tolvaptan (CKD 3-4) | 1A | REPRISE |
| Hydration (3-4 L/day) | 2C | Physiological rationale, Observational |
| Aneurysm Screening (High-risk) | 2B | Observational studies |
What is ADPKD?
ADPKD (Autosomal Dominant Polycystic Kidney Disease) is an inherited condition where fluid-filled cysts grow in your kidneys. Over time, these cysts get bigger and more numerous, and the kidneys can become very large - sometimes as big as a rugby ball.
Key Points to Understand
| Fact | Explanation |
|---|---|
| Inherited | It runs in families. If a parent has it, Each child has a 50% chance. |
| Cysts = Fluid-filled pockets | Like blisters on your kidney |
| Both kidneys affected | Usually both, Though one may be worse |
| Slow progression | Gets worse over decades, Not suddenly |
| Not cancer | The cysts are benign, Not cancerous |
Why Does it Happen?
It's caused by a gene change (mutation) that you inherit from a parent. If one of your parents has ADPKD, you have a 50% chance of inheriting it. In about 10% of cases, it appears "out of the blue" with no family history (New mutation).
The Two Genes:
- PKD1 (85% of cases) – Tends to cause earlier kidney problems (Around 55-60 years)
- PKD2 (15% of cases) – Usually milder, With later kidney problems (Around 70-75 years)
What are the Symptoms?
Many people have no symptoms for years. Common symptoms include:
| Symptom | What it Feels Like |
|---|---|
| High blood pressure | Often the first sign. May feel nothing but is detectable on measurement. |
| Flank or back pain | Aching or sharp pain in your sides/Back |
| Blood in urine | Pink, Red, or brown urine. Usually from cyst bleeding. |
| Kidney infections | Fever, Pain, Feeling unwell |
| Feeling full quickly | If kidneys are very large |
What Other Problems Can it Cause?
ADPKD can affect other parts of your body too:
| Problem | How Common | What Does it Mean? |
|---|---|---|
| Liver cysts | Very common (Greater than 80%) | Usually cause no problems. Rarely become large. |
| Brain aneurysms | 5-10% | Small bulges in blood vessels. Usually monitored. |
| Heart valve problems | 25% | Usually minor. Rarely need treatment. |
| Hernias | Increased | More common due to big kidneys |
Will My Kidneys Fail?
Eventually, many people with ADPKD will need dialysis or a kidney transplant. This typically happens:
- Around age 55-60 for PKD1 gene
- Around age 70-75 for PKD2 gene
BUT: This is NOT inevitable for everyone. Many things can slow progression.
What I Can Do to Help My Kidneys
| Action | Why it Helps |
|---|---|
| Drink plenty of water (3-4 litres/day) | Helps slow cyst growth |
| Control blood pressure | Very important – Takes pressure off kidneys |
| Reduce salt | Helps blood pressure and fluid |
| Don't smoke | Protects heart and blood vessels |
| Stay active and healthy weight | Overall health |
| Avoid ibuprofen (NSAIDs) | These can damage kidneys |
What Treatment is Available?
| Treatment | What it Does |
|---|---|
| Blood pressure tablets (ACE inhibitors/ARBs) | Controls BP, Protects kidneys |
| Lots of water | Slows cyst growth |
| Tolvaptan | New medicine that slows cyst growth (For selected patients) |
| Pain relief | For cyst pain (Avoid ibuprofen) |
| Antibiotics | If cyst infection |
| Dialysis/Transplant | When kidneys fail |
What is Tolvaptan?
Tolvaptan is a relatively new medication that can slow down cyst growth and kidney decline. It's not for everyone - you need to be assessed to see if it's suitable.
| Question | Answer |
|---|---|
| How does it work? | Blocks a hormone signal that makes cysts grow |
| Who can take it? | People with fast-growing cysts and moderate kidney problems |
| Side effects? | Makes you pee a lot (You need to drink 3-4 litres/day). Need regular blood tests. |
| Does it cure ADPKD? | No, But slows it down |
Should My Family be Tested?
Yes. First-degree relatives (Children, Siblings, Parents) should be offered screening.
| Who | When to Screen | How |
|---|---|---|
| Children of someone with ADPKD | From age 18-20 (Or younger if symptoms) | Ultrasound scan + Blood pressure |
| Siblings | If not already screened | Ultrasound scan |
| If considering pregnancy | Before conceiving if possible | May want genetic counselling |
When to Worry / See a Doctor Urgently
[!CAUTION] See a doctor urgently if you have:
- Severe sudden headache ("Worst headache ever") – Could be a brain bleed
- High fever with flank pain – Could be cyst infection
- Heavy blood in urine with clots
- Very high blood pressure (Greater than 180/110)
- Feeling very unwell
Frequently Asked Questions (FAQs)
| Question | Answer |
|---|---|
| Can I still work? | Yes. Most people live normal lives. Avoid very high-risk jobs (Pilot) if you have aneurysm risk. |
| Can I exercise? | Yes. Moderate exercise is good. Avoid very high-contact sports (Risk of cyst bleeding). |
| Can I have children? | Yes. Pregnancy is usually safe. Discuss with your doctor. Consider genetic counselling. |
| Will my children get it? | 50% chance for each child if you have ADPKD. |
| Can I drink alcohol? | In moderation, Yes. Don't overdo it. |
| Can I take painkillers? | Paracetamol is safe. Avoid ibuprofen/Naproxen (NSAIDs). |
| Will I need a transplant? | Not everyone. Depends on your gene, Progression, And treatment. |
| Is there anything I can do? | Yes! BP control, Hydration, Healthy lifestyle, And possibly Tolvaptan. |
Psychological Impact and Support
Living with ADPKD can be challenging:
| Challenge | Support |
|---|---|
| Anxiety about the future | Speak to your doctor about counselling |
| Genetic guilt (Passing to children) | Genetic counselling can help |
| Pain and fatigue | Pain management, Pacing |
| Impact on work/Life | Occupational health support |
Support Resources:
- PKD Charity (UK): www.pkdcharity.org.uk
- Kidney Care UK: www.kidneycareuk.org
- PKD Foundation (US): www.pkdcure.org
Primary Guidelines
-
Chapman AB, et al. KDIGO Cyst Controversy Conference on ADPKD. Kidney Int. 2015;88(1):17-27. PMID: 25786098
-
Gansevoort RT, et al. Recommendations for the use of tolvaptan in ADPKD: EKA/ERA-EDTA position statement. Nephrol Dial Transplant. 2022;37(12):2303-2316. PMID: 36054816
-
NICE Technology Appraisal TA873. Tolvaptan for treating ADPKD. NICE. 2023.
Landmark Trials
-
Torres VE, et al. Tolvaptan in patients with ADPKD (TEMPO 3:4). N Engl J Med. 2012;367(25):2407-2418. PMID: 23121377
-
Torres VE, et al. Tolvaptan in later-stage ADPKD (REPRISE). N Engl J Med. 2017;377(20):1930-1942. PMID: 29105594
-
Schrier RW, et al. Blood pressure in early ADPKD (HALT-PKD). N Engl J Med. 2014;371(24):2255-2266. PMID: 25399733
Genetics and Pathophysiology
-
Harris PC, Torres VE. Genetic mechanisms and signaling pathways in ADPKD. J Clin Invest. 2014;124(6):2315-2324. PMID: 24892705
-
Cornec-Le Gall E, et al. PKD1 and PKD2 mutations in ADPKD. J Am Soc Nephrol. 2013;24(6):1006-1013. PMID: 23431072
Additional References
-
Irazabal MV, et al. Mayo Classification (HtTKV) for ADPKD. J Am Soc Nephrol. 2015;26(1):160-172. PMID: 25060052
-
Perrone RD, et al. Total kidney volume is a prognostic biomarker in ADPKD. Clin J Am Soc Nephrol. 2017;12(12):2059-2067. PMID: 29074820
-
Chebib FT, Torres VE. ADPKD: Core curriculum 2016. Am J Kidney Dis. 2016;67(5):792-810. PMID: 26786631
-
Pei Y, et al. Unified criteria for diagnosis of ADPKD. J Am Soc Nephrol. 2009;20(1):205-212. PMID: 18945943
-
Ong ACM, Harris PC. A polycystin-centric view of cyst formation and disease. Nat Rev Nephrol. 2015;11(7):395-405. PMID: 25826034
-
Müller RU, Bhutani V. Extrarenal manifestations of ADPKD. Curr Opin Nephrol Hypertens. 2020;29(2):243-249. PMID: 31834119
-
Soroka S, et al. Intracranial aneurysms in ADPKD. Kidney Int. 2013;84(5):903-916. PMID: 23783241
High-Yield Facts for Exams
| Category | Key Point |
|---|---|
| Definition | Most common inherited cause of ESRD |
| Inheritance | Autosomal dominant, 50% risk to offspring |
| Genes | PKD1 (85%) and PKD2 (15%) |
| ESRD | PKD1: 55-60 yrs, PKD2: 70-75 yrs |
| Mechanism | Two-hit hypothesis, cAMP-driven cyst growth |
| First-Line Treatment | ACEi/ARB for hypertension |
| Disease-Modifying | Tolvaptan (V2R antagonist) |
| Most Common Extrarenal | Hepatic cysts (Greater than 80%) |
| Key Complication | Intracranial aneurysm (5-10%) |
| Diagnostic Gold Standard | Ultrasound (Ravine criteria) |
Common Exam Questions
Short Answer Questions:
-
Genetics Question: "A 30-year-old woman has ADPKD. What is her child's risk of inheriting the condition?"
- Answer: 50% (Autosomal dominant inheritance).
-
Diagnostic Criteria: "How many cysts are required for diagnosis in a 45-year-old at-risk individual?"
- Answer: ≥2 cysts in each kidney (Ravine criteria for 40-59 years).
-
Disease-Modifying Therapy: "What medication slows cyst growth in ADPKD and what is its mechanism?"
- Answer: Tolvaptan – Vasopressin V2 receptor antagonist. Reduces cAMP in cyst epithelial cells.
-
Screening Question: "Which patients with ADPKD should be screened for intracranial aneurysms?"
- Answer: Those with family history of SAH/Aneurysm, High-risk occupations (Pilot, Surgeon), Pre-major surgery, Or symptoms.
-
Blood Pressure Target: "What is the blood pressure target in early ADPKD?"
- Answer: Less than 130/80 mmHg (HALT-PKD). Consider less than 110/75 in young patients with preserved function.
MCQ-Style Questions:
-
First Sign: "What is often the first clinical sign of ADPKD?"
- A) Flank pain
- B) Gross haematuria
- C) Hypertension ✓
- D) Palpable kidneys
- E) Elevated creatinine
-
Best Initial Investigation: "A 25-year-old with family history of ADPKD asks about screening. What is the most appropriate initial investigation?"
- A) CT abdomen
- B) Renal biopsy
- C) Ultrasound kidneys ✓
- D) MRI kidneys
- E) Genetic testing
-
Tolvaptan Monitoring: "Which test is ESSENTIAL to monitor regularly in patients on Tolvaptan?"
- A) Blood pressure
- B) Liver function tests ✓
- C) Renal function
- D) Potassium
- E) Full blood count
OSCE Stations
Station 1: Explaining ADPKD Diagnosis
| Component | Expected Points |
|---|---|
| What it is | Inherited condition causing kidney cysts |
| How inherited | From parent, 50% chance to children |
| What happens | Cysts grow, Kidneys enlarge, May need dialysis/Transplant |
| Treatment | BP control, Hydration, Possibly Tolvaptan |
| Family screening | Offer to first-degree relatives |
Station 2: Counselling for Tolvaptan
| Component | Key Points |
|---|---|
| What Tolvaptan does | Slows cyst growth by blocking vasopressin |
| Who can take it | Fast progressors (Mayo 1C-1E) with CKD 2-3 |
| Side effects | Polyuria (Excessive urination), Thirst |
| Monitoring | Monthly liver blood tests for 18 months |
| Contraindications | Liver disease, Can't drink enough water |
Station 3: Abdominal Examination
| Step | Expected Finding |
|---|---|
| Inspection | May see abdominal distension |
| Palpation | Bilateral ballotable renal masses (Pathognomonic) |
| Liver | May be enlarged (PLD) |
| Hernias | Check for umbilical/Inguinal |
| BP | Check blood pressure (Often elevated) |
Viva Points
Opening Statement:
"Autosomal dominant polycystic kidney disease is the most common inherited cause of end-stage renal disease, caused by mutations in PKD1 (85%) or PKD2 (15%) genes encoding polycystins. It is characterised by progressive bilateral renal cyst development leading to ESRD typically by age 55-60 for PKD1 and 70-75 for PKD2."
Key Facts Table:
| Fact | Detail |
|---|---|
| Prevalence | 1:400-1:1000 |
| Inheritance | Autosomal dominant, 50% risk |
| Pathophysiology | Two-hit hypothesis |
| Most Common Extrarenal | Hepatic cysts (Greater than 80%) |
| Key Complication | Intracranial aneurysms (5-10%) |
| Key Treatment | ACEi/ARB, Tolvaptan |
| Key Trials | HALT-PKD, TEMPO 3:4, REPRISE |
Evidence to Cite:
- "HALT-PKD showed rigorous BP control slowed TKV growth"
- "TEMPO 3:4 showed Tolvaptan reduced TKV growth by 49% and eGFR decline by 26%"
- "REPRISE extended benefit to later CKD stages"
Common Mistakes
What Fails Candidates:
| Mistake | Why It's Wrong |
|---|---|
| ❌ Not knowing PKD1 vs PKD2 differences | PKD1 earlier ESRD (55-60 vs 70-75) |
| ❌ Forgetting extrarenal manifestations | Liver cysts, Brain aneurysms |
| ❌ Not mentioning Tolvaptan | Disease-modifying therapy |
| ❌ Missing aneurysm screening indications | FH of SAH, High-risk job |
| ❌ Confusing ADPKD with ARPKD | ARPKD is childhood, Recessive |
| ❌ Not knowing Ravine criteria | Age-specific cyst counts |
Dangerous Errors:
- ⚠️ Missing SAH presentation (Sudden severe headache)
- ⚠️ Not monitoring liver function on Tolvaptan (Hepatotoxicity 1-2%)
- ⚠️ Using NSAIDs in ADPKD (Nephrotoxic)
Examiner Follow-Up Questions
| Question | Model Answer |
|---|---|
| "What is the two-hit hypothesis?" | Germline mutation (1st hit) + Somatic mutation (2nd hit) = Cyst formation. Explains focal nature. |
| "How does Tolvaptan work?" | V2R antagonist → Blocks vasopressin → Reduces cAMP → Slows cyst proliferation and secretion |
| "Why ACEi/ARB first-line?" | Blocks RAAS, Reduces BP, May slow progression, Protects heart |
| "When to screen for aneurysms?" | FH of SAH, FH of ICA, High-risk occupation, Pre-surgery, Symptoms |
| "What is Mayo Classification?" | Risk stratification using height-adjusted TKV. 1A-1E. 1C-1E = Fast progressors. |
Differential Diagnosis
| If Asked... | Answer |
|---|---|
| "What else causes bilateral renal cysts?" | ARPKD (Childhood), Acquired cystic disease, Von Hippel-Lindau, Tuberous sclerosis |
| "How to differentiate ADPKD from simple cysts?" | ADPKD: Multiple, Bilateral, Family history. Simple cysts: Usually one or two, No family history. |
| "What causes polycystic liver?" | ADPKD (Most common), ADPLD (Isolated PLD) |
Last Reviewed: 2025-12-25 | 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 and current guidelines.