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Polycystic Kidney Disease — Viva Questions
Rapid-fire examiner prompts with model answers. Each answer should be delivered in 30-60 seconds.
Definition & Classification
Q. Define ADPKD in one sentence. The commonest inherited kidney disease — an autosomal dominant ciliopathy producing bilateral enlarging renal cysts, hypertension and end-stage kidney disease by the fifth or sixth decade, with characteristic extrarenal (liver, brain, heart) manifestations.
Q. What is its prevalence and its share of ESKD? Prevalence 1 in 400 to 1 in 1000 live births; accounts for 5-10 percent of all ESKD — the 4th or 5th leading cause of ESKD.
Q. Name the genes and their chromosomes. PKD1 on chromosome 16p13.3 (85 percent, severe, polycystin-1); PKD2 on chromosome 4q22.1 (15 percent, milder, polycystin-2). Non-PKD genes (ALG8, ALG9, GANAB, DNAJB11, IFT140) account for ~2 percent.
Q. Distinguish ADPKD from ARPKD. ADPKD — autosomal dominant, PKD1/PKD2, adult onset, massively enlarged kidneys with cysts of all sizes, liver cysts. ARPKD — autosomal recessive, PKHD1 (fibrocystin), neonatal onset with huge echogenic fusiform-dilated kidneys, and congenital hepatic fibrosis.
Pathophysiology
Q. Why is ADPKD called a ciliopathy? Because the defective proteins (polycystin-1/2) normally form a calcium-channel complex in the primary cilium of the tubular epithelial cell, where they sense tubular flow and maintain intracellular calcium.
Q. Explain the two-hit model. Inheritance is dominant, but each cyst is focal because a germline mutation in one allele requires a somatic second hit (mutation, loss of heterozygosity, or epigenetic silencing) on the other, wild-type allele to drive cystogenesis.
Q. Trace the intracellular signalling cascade. Loss of polycystin lowers intracellular calcium; calcium fall raises cyclic AMP (disinhibition of adenylyl cyclase 6, inhibition of PDE1); cAMP activates PKA, MAPK/ERK and mTOR driving proliferation, and CFTR-mediated chloride (and fluid) secretion into the cyst lumen.
Q. How does vasopressin drive cyst growth, and how does tolvaptan work? Vasopressin acts on the V2 receptor to stimulate adenylyl cyclase 6, amplifying cAMP. Tolvaptan antagonises the V2 receptor, lowering cAMP and slowing cyst growth.
Clinical Presentation
Q. What is the earliest manifestation of ADPKD? Hypertension — often present at diagnosis (up to 60 percent) and preceding any fall in GFR by years.
Q. Name the four classic extrarenal manifestations. Polycystic liver disease (commonest, ~80 percent by age 60), intracranial berry aneurysm (~10 percent, SAH risk), mitral valve prolapse (~25 percent), pancreatic cysts and diverticular disease.
Q. Why is hypertension early in ADPKD? RAAS activation and reduced renal perfusion from cyst compression, sympathetic overactivity, and endothelial dysfunction (low nitric oxide).
Diagnosis
Q. Give the Pei unified ultrasound criteria in an at-risk relative. Ages 15-39: three or more cysts (unilateral or bilateral); ages 40-59: two or more cysts in each kidney; age over 60: four or more cysts in each kidney. Mnemonic: 3-2-4.
Q. What is the Mayo imaging classification and what is its use? A prognostic stratification by height-adjusted total kidney volume into typical class 1 (1A slowest to 1E most rapidly enlarging) and atypical class 2. Class 1C-1E defines rapidly progressive disease and is a key trigger for tolvaptan.
Q. When do you request genetic testing? Atypical or mild phenotype, very early onset, no family history, evaluation of a potential living related kidney donor, and reproductive counselling (preimplantation genetic diagnosis).
Q. Who should be screened for an intracranial aneurysm? Selective, not routine: family history of aneurysm or SAH, prior rupture, uncontrolled hypertension, smoker, age over 50, high-risk occupation, or before major surgery. Use MRA.
Complications
Q. A 42-year-old man with ADPKD has a thunderclap headache. Diagnosis and immediate action? Subarachnoid haemorrhage from a ruptured berry aneurysm until proven otherwise. Emergency non-contrast CT; LP for xanthochromia if CT negative; neurosurgical / interventional referral; BP control; endovascular coiling or surgical clipping.
Q. How does a cyst infection present and how do you treat it? Fever, flank pain, a tender kidney, positive blood or urine cultures. Treat with a cyst-penetrating antibiotic — ciprofloxacin 500 mg BD, clindamycin, or chloramphenicol for at least 2 weeks; drain a 3-5 cm or larger infected cyst. Avoid aminoglycosides and beta-lactams alone.
Q. Why is macroscopic haematuria common and how do you manage it? Cyst haemorrhage into the collecting system (~40 percent lifetime risk of an episode). Manage with bed rest, hydration, analgesia (paracetamol ± opioid, AVOID NSAIDs), stop anticoagulants, tranexamic acid for refractory bleeding, and selective renal arterial embolisation if life-threatening.
Management
Q. What is the blood pressure target and first-line drug? Under 110/80 mmHg in adults with eGFR over 30 (HALT-PKD). First-line an ACE inhibitor OR ARB (not both), with a long-acting dihydropyridine calcium-channel blocker second-line.
Q. Give the dose, monitoring and contraindications of tolvaptan. Start 45/15 mg split dose, titrate monthly to 60/30 then 90/30 mg per day. Monitor transaminases monthly for 18 months then 3-monthly; monitor serum sodium and aquaresis. Avoid in pregnancy, hypovolaemia, hypernatraemia, hepatic impairment, and inability to perceive thirst.
Q. Why must you avoid NSAIDs in ADPKD? They accelerate chronic kidney disease, increase bleeding (especially with cyst haemorrhage), and antagonise the antihypertensive effect of ACE inhibitors/ARBs.
Q. What are the options for symptomatic polycystic liver disease? Cyst aspiration-sclerotherapy, laparoscopic fenestration, hepatic resection, selective hepatic artery embolisation, somatostatin analogue (lanreotide/octreotide), liver transplant for massive disease.
Prognosis & Donor Evaluation
Q. What is the median age at ESKD by genotype? PKD1 truncating ~55 years; PKD1 non-truncating ~65 years; PKD2 ~74 years.
Q. How do you evaluate an at-risk relative as a living kidney donor? Use both age-appropriate imaging and genetic testing of the known familial variant. An at-risk relative under 30 needs both; an affected relative must not donate.
Pearls
Q. Thunderclap headache + ADPKD? Subarachnoid haemorrhage — emergency non-contrast CT.
Q. Most common extrarenal manifestation? Liver cysts.
Q. The drug that slows rapidly progressive ADPKD? Tolvaptan — a V2-receptor antagonist; monitor LFTs.