Hereditary and Cystic Kidney Disease — Advanced

Correct: Autosomal dominant conditions such as ADPKD are transmitted in a vertical autosomal dominant pattern; each child of an affected parent has a 50% chance of inheriting the pathogenic allele, independent of the parent’s disease severity. Option A is incorrect because 25% is the risk for autosomal recessive inheritance with both parents carriers, not ADPKD. Option C is incorrect because disease severity in the parent does not change the probability of transmission; there is variable expressivity but not altered Mendelian transmission. Option D is incorrect because although penetrance is high for many ADPKD mutations, penetrance is not absolute in all cases and disease expression varies; the correct point is the 50% transmission risk rather than certainty. Option E is incorrect because parental age at diagnosis does not change the Mendelian 50% transmission risk.

Correct: MRI provides high-resolution, reproducible kidney and cyst volume measurements without ionising radiation and is the preferred modality for accurate serial measurement of total kidney volume in ADPKD. Ultrasound is useful for screening but is operator-dependent and not reliable for precise TKV quantification. Non-contrast CT gives good anatomical detail but involves ionising radiation and is less preferred for repeated measurements. Nuclear renography assesses split function rather than morphology or volume. Plain radiograph does not provide kidney volume information.

Correct: Renin–angiotensin system blockade (ACE inhibitor or ARB) is first-line antihypertensive therapy for patients with ADPKD, particularly when there is proteinuria, because it both lowers blood pressure and reduces intraglomerular pressure/proteinuria. Beta-blockers and calcium-channel blockers may be used as add-on agents but are not preferred first-line when RAAS blockade is indicated. Loop diuretics are reserved for volume overload and are not standard initial therapy for hypertension alone. Lifestyle measures are important but insufficient here given persistent clinic hypertension and significant proteinuria.

Correct: Tolvaptan is a selective vasopressin V2 receptor antagonist that reduces cAMP-mediated cyst growth and causes aquaresis (increased free water clearance). A recognized safety concern is idiosyncratic liver injury, so regular liver function testing is required during treatment and treatment should be stopped if significant liver enzyme rises occur. Option A confuses tolvaptan with mTOR inhibitors (e.g., sirolimus), which have a different mechanism and adverse effect profile. Option B incorrectly labels it as an immunosuppressant. Option D is incorrect; ADPKD is not treated with enzyme replacement. Option E incorrectly equates tolvaptan with loop diuretics; its mechanism is via V2 antagonism and it causes aquaresis rather than natriuresis.

Correct: Antibiotics that penetrate cyst fluid well, notably fluoroquinolones (e.g., ciprofloxacin) and trimethoprim-sulfamethoxazole, are preferred empiric choices for suspected infected cysts in ADPKD. Many beta-lactams and aminoglycosides penetrate cysts poorly, making them less suitable as sole empiric therapy. Metronidazole targets anaerobes and is not appropriate as monotherapy for renal cyst infection. Definitive therapy should be guided by cultures and clinical response, and large infected cysts may require percutaneous drainage.

Correct: Somatostatin analogues have been shown to reduce liver cyst growth and liver volume in some patients with symptomatic polycystic liver disease and are an option in selected patients, particularly when conservative measures have failed and before considering major surgery. Option A (immediate liver transplant) is reserved for very severe refractory cases with liver failure or unacceptable quality-of-life impairment and is not first-line. Corticosteroids are not effective for cyst reduction. mTOR inhibitors have had mixed results and are not routinely used as standard therapy for PLD. Option E is incorrect because there are effective medical options for some patients (e.g., somatostatin analogues) and interventional/surgical options for others.

Correct: ARPKD in the neonate commonly presents with pulmonary hypoplasia secondary to oligohydramnios; the immediate priority is respiratory stabilisation and supportive care in a neonatal intensive care setting. Nephrectomy is not an initial intervention and is rare acutely; ACE inhibitors are used later to manage hypertension but are not the immediate priority in a crashing neonate. Dialysis decisions are complex in the neonatal period and depend on overall prognosis and stability; immediate chronic peritoneal dialysis is not the first step in the acute respiratory-compromised infant. High-dose diuretics will not effectively reduce massively enlarged dysplastic kidneys and are not indicated acutely.

Correct: When a pathogenic familial mutation is known, targeted genetic testing of at-risk potential living donors is appropriate and can definitively determine whether the donor carries the family mutation; a donor who is mutation-positive should not donate. Option A is incorrect because family members can donate if they are proven not to carry the pathogenic mutation. Option B is unsafe because ultrasound may be normal in younger mutation carriers and cannot exclude presymptomatic disease reliably for all ages. Option D is inappropriate because WES is not routine for donor assessment and may identify unrelated incidental findings; targeted testing is the recommended focused approach. Option E is unsafe because normal blood pressure does not exclude a pathogenic mutation and future risk for kidney disease.

Correct: In haemodynamically stable patients with gross haematuria from ADPKD, initial management is usually conservative (rest, hydration, analgesia, and observation) because haematuria often results from cyst rupture and will settle. Intervention (angiographic embolisation, surgery or endoscopic procedures) is reserved for ongoing or severe bleeding, haemodynamic instability, or specific lesions identified on imaging. Immediate angiography or nephrectomy is not indicated if the patient is stable. Anticoagulation is contraindicated in active bleeding unless there is a compelling separate indication. ESWL is for renal stones and is not appropriate for presumed cyst-related haematuria without confirmation.

Correct: For suitable candidates, pre-emptive kidney transplantation is the preferred long-term renal replacement therapy because it provides best outcomes and quality of life. Peritoneal dialysis is not universally contraindicated in ADPKD though very large kidneys can limit intraperitoneal volume and require individual assessment; it remains a viable modality for many patients. Haemodialysis is an acceptable RRT but not the only option. Native nephrectomy is not routinely required prior to transplantation and is performed selectively for symptom control or technical reasons. Kidney disease does not recur in the graft from ADPKD; there is no reason to deny listing on the basis of ADPKD alone.