Polycystic Kidney Disease — Short Answer Questions (NEET-PG / INICET)

SAQ 1 — Define ADPKD, state its inheritance and gene, and give the median age of ESKD by genotype

Definition. Autosomal dominant polycystic kidney disease (ADPKD) is the commonest inherited kidney disease (prevalence 1 in 400-1 in 1000), characterised by bilateral, progressively enlarging renal cysts arising from any nephron segment, with extrarenal cystic and non-cystic manifestations, leading to hypertension and end-stage kidney disease in the majority by the fifth or sixth decade.

Inheritance. Autosomal dominant; de novo mutations in 5-10 percent. Fully penetrant (essentially 100 percent by age 70 with modern imaging), variable expressivity.

Gene and median age at ESKD.

PKD1 accounts for ~85 percent and PKD2 for ~15 percent of families; non-PKD genes (ALG8, ALG9, GANAB, DNAJB11, IFT140) account for ~2 percent of clinically diagnosed ADPKD.

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SAQ 2 — A 35-year-old woman with PKD1 ADPKD, Mayo class 1D, has an eGFR of 70 mL/min/1.73 sq m that is falling by 4 mL/min/1.73 sq m per year. Discuss the rationale, evidence, dosing and monitoring of tolvaptan

Rationale. Tolvaptan is a selective vasopressin V2-receptor antagonist. Vasopressin drives cAMP generation in the collecting duct; cAMP promotes cyst-cell proliferation and CFTR-mediated chloride (and fluid) secretion. By blocking the V2 receptor, tolvaptan lowers intrarenal cAMP, slowing cyst growth and eGFR decline. The patient above meets criteria for rapidly progressive ADPKD (PKD1 truncating, Mayo 1D, eGFR decline over 2.5-3 mL/min/1.73 sq m/yr, preserved eGFR).

Evidence.

• TEMPO 3:4 (Torres 2012, NEJM, PMID 23121377): tolvaptan vs placebo in early ADPKD (eGFR ≥60) — slowed height-adjusted total kidney volume growth and eGFR decline over 3 years.
• REPRISE (Torres 2017, NEJM, PMID 29105594): tolvaptan in later-stage ADPKD (eGFR 25-65) — slowed eGFR decline; similar safety profile.

Net effect: ~2-3 years' delay in ESKD.

Dosing. Split-dose regimen (once-daily tolvaptan causes a peak aquaresis that is poorly tolerated): start 45/15 mg (morning/evening), titrate monthly by aquaresis and tolerance to 60/30 then 90/30 mg per day. Take with free access to water; advise against dehydration.

Monitoring.

• Transaminases (ALT/AST) monthly for the first 18 months, then 3-monthly — hepatotoxicity (ALT >3× ULN) in ~5 percent; usually reversible, rarely severe.
• Serum sodium (rises with aquaresis-driven volume depletion).
• Volume status / weight / thirst / polyuria (expect 3-6 L/day urine output).
• Contraception (teratogenic — withhold in pregnancy).
• eGFR may transiently rise due to aquaresis; assess trend over months.

Contraindications and cautions. Pregnancy, anuria, hypovolaemia, hypernatraemia, hepatic impairment, inability to perceive thirst. KDIGO 2025 and NICE endorse tolvaptan for rapidly progressive ADPKD under specialist supervision.

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SAQ 3 — Outline the Pei unified ultrasound criteria and the Mayo imaging classification of ADPKD

Pei unified age-adjusted ULTRASOUND criteria for an at-risk first-degree relative (positive predictive value ~100 percent):

• Age 15-39 years: 3 or more renal cysts (unilateral or bilateral).
• Age 40-59 years: 2 or more cysts in each kidney.
• Age ≥60 years: 4 or more cysts in each kidney.

Mnemonic: 3-2-4. Without a family history, the criteria are stricter (10 or more cysts in each kidney, or genetic confirmation).

CT / MRI criteria (higher sensitivity): age 15-40 years, 3 or more cysts (bilateral or unilateral); age over 40 years, 5 or more cysts in each kidney.

Mayo imaging classification (prognosis and treatment triage, based on height-adjusted total kidney volume, htTKV, on MRI/CT):

• Class 1 (typical) — bilateral expanding cysts, sub-classified:
  • 1A — slowest (ESKD unlikely before 70).
  • 1B — intermediate.
  • 1C, 1D, 1E — progressively more rapid; 1C-1E is the trigger for tolvaptan.
• Class 2 (atypical) — bilateral cysts not meeting the typical pattern (asymmetric, segmental, lopsided); consider mimics and non-PKD genes.

MRI is the preferred modality for htTKV measurement; ultrasound suffices for screening.

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SAQ 4 — A 45-year-old man with ADPKD develops fever, right flank pain and a tender right kidney. Discuss the diagnosis and management of an infected renal cyst

Diagnosis. Suspect an infected cyst in any ADPKD patient with fever, flank pain, a tender enlarged kidney, and positive blood or urine cultures. CT or MRI (with contrast, if eGFR permits) shows a cyst with surrounding inflammatory stranding, a thick enhancing wall, gas, or layering debris; FDG-PET/CT or white-cell scintigraphy localises occult infected cysts. Distinguish from acute pyelonephritis, cyst haemorrhage (no fever, no positive culture), and renal cell carcinoma (Bosniak III/IV).

Management.

• Blood and urine cultures before antibiotics; analgesia and antipyretics.
• Cyst-penetrating antibiotic — ciprofloxacin 500 mg PO BD (or 400 mg IV BD); alternatives clindamycin 600 mg IV TDS, chloramphenicol. Continue for at least 2 weeks (often 4-6 weeks for deep infection). Aminoglycosides and beta-lactams alone penetrate cyst fluid poorly and should not be sole therapy.
• Image-guided drainage of an infected cyst 3-5 cm or larger, or that fails to improve on antibiotics.
• Switch to culture-directed therapy once sensitivities are available.
• Treat any predisposing factor (e.g. nephrolithiasis, obstruction).
• Recurrent infection, refractory pain, or massive haemorrhage may warrant nephrectomy (including before transplant to make room).

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SAQ 5 — A 30-year-old pregnant woman with ADPKD is referred for pre-conception counselling. Outline the key issues and management plan

Pre-conception counselling.

• Genetic risk — each child has a 50 percent chance of inheriting the familial PKD1/PKD2 variant; offer prenatal diagnosis or preimplantation genetic testing if desired.
• Maternal renal status — optimise blood pressure and proteinuria before conception; eGFR over 60 and BP under 140/90 without proteinuria are reassuring.
• Drugs — stop ACE inhibitors and ARBs pre-conception (teratogenic — renal dysplasia, oligohydramnios, pulmonary hypoplasia). Switch to labetalol, methyldopa, or nifedipine. Stop tolvaptan (no safety data; aquaresis may compromise placental perfusion). Avoid NSAIDs.
• Hypertension — BP target under 140/90 in pregnancy; monitor closely.
• Pregnancy complications — modestly increased risk of gestational hypertension, pre-eclampsia, and urinary tract infection; large kidneys rarely obstruct labour.
• Contraception — progesterone-only pills or intrauterine device preferred; oestrogen-containing combined pills may worsen hypertension (use cautiously).
• Antenatal care — joint nephrology-obstetric care; serial BP and urinalysis; urine culture each trimester; serial growth scans.
• Aneurysm screening — consider MRA before pregnancy if family history of SAH, to avoid the imaging dilemma in pregnancy.

Intrapartum and postpartum — usual obstetric management; caesarean only for obstetric indications (large kidneys rarely obstruct labour); resume ACEi/ARB postpartum only if not breastfeeding (ACEi/ARB excreted in breast milk; limited safety data).

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SAQ 6 — Outline the cardiovascular and cerebrovascular complications of ADPKD and the strategy for intracranial aneurysm screening

Cardiovascular.

• Hypertension (the commonest and earliest manifestation; ~60 percent at diagnosis).
• Left ventricular hypertrophy from long-standing hypertension.
• Mitral valve prolapse (~25 percent), aortic regurgitation, tricuspid regurgitation.
• Aortic root dilatation and rarely dissection.

Cerebrovascular.

• Intracranial berry aneurysm in ~10 percent of ADPKD patients (vs ~1-2 percent in the general population), with rupture → subarachnoid haemorrhage (case fatality 30-50 percent). Risk factors: family history of aneurysm/SAH, prior rupture, uncontrolled hypertension, age over 50, female sex, smoking.

Screening strategy. Screening is selective, not routine.

• Screen by MRA (time-of-flight, no contrast) or CTA if any of: family history of intracranial aneurysm or SAH; prior aneurysm rupture or known aneurysm; uncontrolled hypertension; smoker; age over 50; high-risk occupation (e.g. pilot); before major elective surgery or transplant work-up; at patient request after counselling.
• Surveillance of a known aneurysm by serial MRA every 2-5 years depending on size and location.
• Intervention for aneurysms over 7 mm, growing, symptomatic, or in high-risk locations — endovascular coiling (preferred for most aneurysms under 10 mm and posterior circulation) or surgical clipping.
• Strict BP control, smoking cessation for all.

Thunderclap headache in any ADPKD patient = subarachnoid haemorrhage until proven otherwise — emergency non-contrast CT; LP for xanthochromia if CT negative.