Polycystic Kidney Disease (PKD)

The most common inherited renal disease, and the most common monogenic cause of kidney failure — accounting for roughly 6% of Australians on dialysis or with a transplant. Two distinct genetic forms exist, with very different presentations.

Autosomal dominant (adult) form (ADPKD)

Both kidneys are always affected; mutations in PKD1 or PKD2. Cysts develop over the patient’s lifetime. PKD1 mutations account for around 78% of cases and PKD2 for around 14%; PKD1 disease is more aggressive, with a mean age at kidney failure of ~54 years versus ~74 years for PKD2. ~15% of patients have no identifiable family history (new mutations, or unknown family history). Penetrance approaches 100% by the 7th–8th decade. ADPKD occurs in roughly 1 in 1,000 births; because many cases run a benign course, fewer than half of affected people are ever diagnosed.

Diagnostic imaging criteria (Pei–Ravine unified ultrasound criteria) by age:

Age	USS criteria
15–39	≥3 cysts total
40–59	≥2 cysts in each kidney (>4 total)
60+	≥4 cysts in each kidney (>8 total)

Ultrasound alone is sufficient for diagnosis in a patient with a positive family history; genetic testing is reserved for family planning or genuine diagnostic uncertainty (e.g. no family history, or an equivocal scan).

Screening is not routinely recommended in asymptomatic family members on renal grounds alone, since imaging findings don’t change early management. This has become less clear-cut since tolvaptan became available: earlier identification of at-risk young adults now opens the door to earlier disease-modifying treatment, so screening decisions increasingly involve the person’s own preference as much as a fixed rule. Screening is recommended for intracranial aneurysm specifically (see below) where there’s a relevant family history.

Autosomal recessive (infantile) form

Relatively rare; usually diagnosed at birth or in-utero by enlarged kidneys.

Extra-renal manifestations and associations

ADPKD is a systemic disease, not just a renal one — extra-renal complications drive much of its morbidity:

• Hepatic cysts — the most common extra-renal manifestation; present in up to 94% of patients over 35, more prevalent and more severe in women. Rarely causes liver dysfunction, though occasional cyst infection or haemorrhage occurs.
• Intracranial aneurysm — 8–12% lifetime risk (StatPearls cites up to 5% in young adults, rising to ~20% over age 60), 4–5× the general population risk. If a family history of aneurysm or subarachnoid haemorrhage exists in a first-degree relative, risk is higher still and screening (MRA) is recommended at diagnosis.
• Cardiac valvular disease (mitral/aortic regurgitation or prolapse) in 25–30% of patients.
• Diverticular disease (~40%) and abdominal wall hernias (inguinal, incisional or para-umbilical, ~45%), partly related to increased abdominal girth from enlarged kidneys.
• Depression — reported in up to 60% of patients, related to chronic pain, disease burden and reduced quality of life; worth screening for at review.
• Elevated cardiovascular risk (~50%) from the combination of hypertension, CKD and valvular disease — premature cardiovascular disease is a leading cause of death in ADPKD.

Presentation

Family history of PKD; typically progresses to end-stage renal disease by the 5th–6th decade. Macroscopic haematuria (particularly after contact sports), unexplained back pain, hypertension. Chronic flank, abdominal or back pain affects around 60% of patients before age 40, and is often multifactorial — capsular distension from expanding cysts, mechanical strain from enlarged kidneys (which can weigh 1–3 kg each), or pain unrelated to the kidneys (hernia, reflux, diverticulitis). New acute severe pain instead suggests a cyst rupture, cyst or urinary infection, or renal colic from a stone, and warrants imaging and urine microscopy/culture.

Investigations

Renal ultrasound, UEC, urine ACR, LFTs (PKD can also affect the liver). Genetic testing is not routine — reserve it for family planning or where the diagnosis is unclear (no family history, atypical imaging). The main differential for bilateral renal cysts is simple/complex renal cysts, localised cystic disease, acquired cystic disease of dialysis, and — where a cyst looks atypical — renal malignancy, stratified using the Bosniak classification.

Management

• Refer to nephrology early for formal diagnosis
• Lifestyle: low-salt diet, adequate fluid intake, smoking cessation
• Blood pressure control
• Tolvaptan (a vasopressin V2 receptor antagonist) can be used early in disease (CKD stage 2–3) — demonstrated to slow cyst development/eGFR decline versus placebo. Requires specialist initiation and monitoring for hepatotoxicity (elevated bilirubin/ALT); PBS criteria and current dosing should be checked at the point of prescribing
• Nephrology follow-up for ongoing monitoring and dialysis preparation when needed

Blood pressure targets are tighter than general CKD: 120/70–130/80 mmHg for early-stage disease (eGFR >60), with a lower target of 110/75 acceptable if tolerated without symptomatic hypotension; 120/70–130/80 mmHg also applies in more advanced disease (eGFR 25–60). ACE inhibitors or ARBs are first-line; thiazides or calcium-channel blockers can be added second-line (they are not contraindicated, contrary to older teaching).

Tolvaptan detail: PBS-subsidised criteria require nephrologist initiation, an eGFR of 30–89 mL/min/1.73m² at the time of starting, and evidence of rapidly progressing disease (eGFR decline >5 mL/min/1.73m² over 1 year, or >2.5 mL/min/1.73m²/year over 5 years). Two imaging/genetic tools — the Mayo Clinic Classification and the PROPKD score — can help predict longer-term kidney failure risk and inform which patients are likely to benefit. Dosing is a split-dose regimen, uptitrated from 60 mg/day (45 mg morning/15 mg evening) to 90 mg then 120 mg/day as tolerated. Aquaresis (5–7 L/day urine output) occurs in essentially all patients and is the main reason for discontinuation (~23% in the pivotal trials); idiosyncratic hepatotoxicity occurs in roughly 5%, so LFTs should be checked before starting, monthly for the first 18 months, then three-monthly thereafter. Note that adults with ADPKD were specifically excluded from the major SGLT2-inhibitor CKD outcome trials, so that evidence base doesn’t directly extend to ADPKD.

Chronic pain should be screened for at every review — it’s easily overlooked. Manage with a standard non-cancer chronic pain ladder (paracetamol, then NSAIDs, then adjuvants); NSAID use should be limited to a maximum of five continuous days per episode in CKD stages 1–3 (case-by-case in stages 4–5) to avoid precipitating acute-on-chronic kidney injury, and analgesic dosing should be adjusted for eGFR. A large dominant cyst (>5 cm) causing localised pain may respond well to radiological aspiration. Refer to a pain specialist if refractory.