Autosomal dominant polycystic kidney disease

At a glance

• The commonest inherited kidney disease, affecting about 1 in 1,000 people, and a leading cause of kidney failure in Australia (see Chronic kidney disease).
• Autosomal dominant: each child of an affected parent has a 50% risk. About 10 to 15% have no family history (de novo variant or a mildly affected parent).
• Diagnosis is usually by ultrasound cyst count for age in someone with a family history. Genetic testing helps when imaging is equivocal or a living related donor is being assessed.
• Kidney function stays normal for decades while cysts grow. Total kidney volume rises first, so eGFR is a late marker.
• Tolvaptan is the only disease-modifying drug, for adults at risk of rapid progression. Everyone else gets BP control, water, salt restriction and weight management.
• Extrarenal problems: liver cysts (the commonest), intracranial aneurysms, mitral valve prolapse, hernias, diverticular disease.

Genetics and nomenclature

Gene	Protein	Share of genetically resolved cases	Typical course
PKD1 (chromosome 16)	Polycystin-1	About 75 to 80%	Kidney failure in the mid-50s if truncating, late 60s if non-truncating
PKD2 (chromosome 4)	Polycystin-2	About 15%	Fewer cysts, later hypertension, kidney failure around 80 if at all
GANAB, DNAJB11, IFT140, ALG9 and others	Various	Small	Mild cystic disease; DNAJB11 gives small fibrotic kidneys; often more liver than kidney disease

• KDIGO 2025 introduced gene-based naming: ADPKD-PKD1, ADPKD-PKD2 and so on. Untested people are still called ADPKD.
• Polycystins sit on the primary cilium. Loss of function lowers intracellular calcium and raises cyclic AMP, which drives cyst epithelial proliferation and fluid secretion. Vasopressin raises cAMP through the V2 receptor, which is why tolvaptan and high water intake are used.
• A cyst forms when the second (somatic) allele is lost in a tubular cell: the two-hit model explains why only some nephrons become cysts.
• PKD1/TSC2 contiguous gene deletion gives severe infantile polycystic kidneys with tuberous sclerosis.

Differential diagnosis of cystic kidneys

Condition	Clue
Simple cysts	Common with age; few, no kidney enlargement, no family history
Acquired cystic kidney disease	Long-term dialysis; small kidneys; raised renal cell carcinoma risk
Tuberous sclerosis	Angiomyolipomas, skin and neurological signs
Von Hippel-Lindau	Complex cysts, renal cell carcinoma, phaeochromocytoma, CNS haemangioblastoma
HNF1B disease	Cysts with hypomagnesaemia, early diabetes (MODY 5), genital tract anomalies
ADTKD (UMOD, MUC1)	Small or normal kidneys, bland urine, gout in UMOD
ARPKD	Large echogenic kidneys in infancy, congenital hepatic fibrosis
ADPLD (PRKCSH, SEC63)	Many liver cysts, few or no kidney cysts, normal kidney function

Recognition

• Hypertension is often the first sign, in the 20s and 30s, before eGFR falls. Renin-angiotensin activation from cyst compression drives it.
• Flank or abdominal pain: acute (cyst haemorrhage, infection, stone) or chronic (capsule stretch, mass effect).
• Visible haematuria from cyst rupture, typically settling within a week with rest and fluids.
• Kidney stones in about 20 to 30%: uric acid and calcium oxalate, helped by low urine pH and hypocitraturia.
• Urinary concentrating defect and polyuria early. Proteinuria is usually under 1 g/day; heavier proteinuria needs a search for a second kidney disease.
• Palpable bilateral flank masses, and hepatomegaly from liver cysts.

Investigations

Diagnosis in someone with a family history (KDIGO 2025, Pei criteria)

Age	Ultrasound cysts to diagnose	Ultrasound to exclude
15 to 29	3 or more in total	No cysts (NPV only about 91% if gene unknown)
30 to 39	3 or more in total	No cysts
40 to 59	2 or more in each kidney	Fewer than 2 cysts in total
60 or over	4 or more in each kidney

• MRI at 16 to 40: 10 or more cysts diagnoses ADPKD; fewer than 5 excludes it.
• Genetic testing (targeted sequencing panel) when imaging is equivocal, there's no family history, the presentation is atypical (very early onset, asymmetric disease), or a young relative wants to donate a kidney.
• No family history and incidental cysts: image both kidneys and the liver, and consider the differentials above.
• Pitfall: a normal ultrasound in an at-risk 25-year-old does not exclude ADPKD. For a living donor workup, use MRI or genetics.

Prognosis

• Height-adjusted total kidney volume (htTKV) on MRI or CT, ideally measured by a validated tool or the ellipsoid formula.
• Mayo imaging classification (KDIGO recommendation 1.4.2.1): class 1A to 1E by htTKV for age. 1C to 1E predict rapid progression (expected annual kidney growth over 3%). Only use it in typical (class 1) disease with PKD1 or PKD2.
• PROPKD score (0 to 9): male sex, hypertension before 35, a urological event before 35, and genotype. A score over 6 marks high risk.
• eGFR slope over several years, after excluding other causes of decline (uncontrolled BP, diabetes, AKI, proteinuria of 1 g/day or more).
• Family history of kidney failure before 60 in two or more relatives suggests a severe family genotype.

Management

Everyone

• BP (KDIGO 2025, based on HALT-PKD):
  • Aged 18 to 49 with eGFR over 60 and BP over 130/85: target 110/75 or less on home monitoring, if tolerated.
  • Aged 50 or over: office systolic under 120, if tolerated.
  • ACE inhibitor or ARB first. Never combine them (HALT-PKD study B found no added benefit). For more detail see Hypertension in kidney disease.
• Water intake of at least 2 to 3 L/day spread through the day if eGFR is 30 or more, to suppress vasopressin (weak evidence, grade 2D; PREVENT-ADPKD showed no clear benefit). Drink to thirst below eGFR 30 or with a risk of hyponatraemia.
• Sodium under 2 g/day (about 5 g salt), healthy weight (obesity speeds progression), no smoking, and alcohol within limits.
• Standard CKD care for anaemia, bone disease, lipids and vaccination (see Delaying CKD progression).
• Avoid NSAIDs for chronic pain. Try simple measures and paracetamol first, then refer to pain or urology services. Cyst aspiration, sclerotherapy or nephrectomy are options for refractory pain.

Tolvaptan

	KDIGO 2025	PBS (Australia; restriction checked November 2026)
eGFR to start	25 or more	30 to 89 (CKD stage 2 to 3)
Rapid progression	Mayo class 1C to 1E, or eGFR decline of 3 or more per year	eGFR decline of 5 or more in 1 year, or an average of 2.5 or more per year over 5 years
Prescriber		Nephrologist; authority required
Age	Over 55: shared, individualised decision (no benefit in the REPRISE subgroup over 55)	No age limit
Stopping	Before pregnancy, during breastfeeding, and at kidney replacement therapy. Can continue past 55 or below eGFR 25 once started	eGFR under 15, or kidney transplant

• Mechanism: a vasopressin V2 receptor antagonist that lowers cAMP in collecting duct cysts.
• TEMPO 3:4 (2012): 1,445 adults aged 18 to 50 with TKV of 750 mL or more and creatinine clearance of 60 mL/min or more. Kidney growth halved (2.8% v 5.5% per year) and kidney function declined more slowly.
• REPRISE (2017): 1,370 adults with later disease (eGFR 25 to 65). eGFR fell 1.3 mL/min/1.73 m² less over one year than with placebo. The 190 participants over 55 got no benefit.
• Dosing: start 45 mg on waking and 15 mg 8 hours later, titrating to 90 mg and 30 mg. These doses are far higher than those used for SIADH (see Hyponatraemia and hypernatraemia).
• Aquaresis: urine output of 4 to 6 L/day, thirst and nocturia. It is the commonest reason to stop. Drink to thirst, including overnight; skip doses on sick days.
• Idiosyncratic hepatotoxicity: ALT over 3 times the upper limit in about 5% (v 1% on placebo). Check LFTs at baseline, monthly for 18 months, then 3-monthly.
• Contraindications: liver disease, hypovolaemia, hyponatraemia, inability to sense or respond to thirst, pregnancy and breastfeeding, and strong CYP3A4 inhibitors (clarithromycin, ketoconazole). It also raises urate.
• Creatinine rises a little after starting from a haemodynamic effect. That isn't treatment failure.
• Pitfall: the PBS and KDIGO criteria differ. A 45-year-old with Mayo class 1D and stable eGFR 70 meets KDIGO but not the PBS eGFR-slope criterion.

Treatments that don't slow ADPKD

KDIGO 2025 advises against mTOR inhibitors, statins and metformin given specifically to slow progression (still use statins for cardiovascular risk and metformin for diabetes as usual), and against somatostatin analogues given for that reason alone. SGLT2 inhibitors shouldn't be used to slow ADPKD; DAPA-CKD and EMPA-KIDNEY excluded it.

Kidney failure

• Transplant is the preferred kidney replacement therapy. Native nephrectomy only for specific reasons: no room for the graft, recurrent infection or bleeding, intractable pain, or suspected cancer. Unilateral nephrectomy is preferred.
• Peritoneal dialysis remains possible for most patients despite large kidneys. Very large kidneys or hernias are relative barriers (see Haemodialysis and peritoneal dialysis).
• Screen relatives under 40 with MRI or genetics before living related donation.

Complications

Kidney

• Cyst haemorrhage: pain and visible haematuria without fever. Treat with rest, fluids and analgesia, and hold antiplatelet or anticoagulant drugs if bleeding persists.
• Cyst infection: fever, localised tenderness, raised CRP. Urine culture is often negative because the cyst doesn't drain. Ultrasound and CT often can't pick out the infected cyst; FDG PET-CT is the most useful imaging. Treat with a lipid-soluble antibiotic (fluoroquinolone or trimethoprim-sulfamethoxazole) for 4 to 6 weeks, and drain large cysts that don't respond.
• No clear excess of renal cell carcinoma in ADPKD itself. The risk rises with acquired cystic disease on dialysis.

Extrarenal

• Polycystic liver disease: cysts on MRI in about 85% of those aged 25 to 34 and over 90% of those aged 35 to 46 (CRISP). Usually silent, with normal liver function. Women have larger livers: oestrogen exposure and pregnancies drive growth. Counsel about contraception: avoid oestrogen where liver cysts are significant, progestogens may also contribute, and non-hormonal options suit those with large livers. Don't restrict contraception in adolescents and young adults. Long-acting somatostatin analogues for severe volume symptoms (off-label and not PBS-subsidised for this use in Australia); liver transplant (sometimes combined kidney-liver) for massive disease.
• Intracranial aneurysm: prevalence about 13% in ADPKD, 17% or more with a family history, versus about 3% in the general population. Rupture often occurs at a younger age than in sporadic disease. Teach everyone to recognise thunderclap headache. Screen with non-contrast MRA (or high-resolution CTA) if there's a personal history of SAH or a family history of aneurysm, SAH or unexplained sudden death, and the person is fit for treatment. Also discuss it with de novo ADPKD, an unknown family history or few affected relatives, and an extracerebral vascular phenotype, and screen before pregnancy planning in women at higher risk. Consider it before transplant or major surgery, in high-risk jobs, and on request (see Intracerebral and subarachnoid haemorrhage).
• Cardiac: mitral valve prolapse, aortic root dilatation, and LV hypertrophy from early hypertension. Echo if there's a murmur, uncontrolled hypertension, or a family history of thoracic aortic aneurysm.
• Other: inguinal and abdominal wall hernias, colonic diverticula (with higher perforation risk after transplant), pancreatic and seminal vesicle cysts, and male infertility.

Special populations

• Pregnancy: higher risk of pre-eclampsia and preterm birth, especially with hypertension or eGFR below 60. Stop tolvaptan and ACE inhibitors or ARBs before conception. Offer preconception counselling, including preimplantation genetic testing where the family variant is known. Pregnancy can enlarge liver cysts.
• Children of affected parents: check BP regularly. Presymptomatic imaging of asymptomatic children is a shared decision, because there's no proven treatment under 18 and it has psychological effects. An imaging diagnosis, like a family history, can still be used in life insurance underwriting; a genetic result can't.
• Aboriginal and Torres Strait Islander people: kidney failure is common but mostly diabetic. Still ask about family history of kidney failure.
• Insurance: since 8 October 2026, Australian life insurers can't ask for or use genetic test results when underwriting death, TPD, trauma or income protection cover (Insurance Contracts Act s 33H). They can still use family history, symptoms and an existing diagnosis such as cysts on imaging. Health insurance is community rated.

Pitfalls

• Excluding ADPKD in a young at-risk relative on a normal ultrasound.
• Blaming every eGFR fall on ADPKD. Check for NSAIDs, uncontrolled BP, obstruction from a stone, or a second disease, especially with proteinuria over 1 g/day.
• Treating fever and flank pain as simple pyelonephritis with a short course of a beta-lactam. Cyst infection needs a lipid-soluble agent for weeks.
• Missing hyponatraemia when advising high water intake in advanced CKD or with thiazide use.
• Recommending an oestrogen-containing contraceptive to a woman with large liver cysts.
• Forgetting aneurysm screening in someone with a family history of SAH or sudden death.