Autosomal dominant polycystic kidney disease

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Pathogenic variants, most often in PKD1 or PKD2, disrupt tubular ciliary signalling and permit progressive cyst expansion. Enlarged kidneys compress functioning tissue and activate pathways that promote hypertension and fibrosis. Liver cysts are common; intracranial aneurysm, cardiac-valve abnormalities, abdominal wall hernia and diverticular disease are recognised extrarenal associations of varying clinical importance.

Imaging must be interpreted against age and prior probability. In someone with an affected first-degree relative, validated ultrasound criteria can confirm or sometimes exclude disease. Without a family history, bilateral cysts require consideration of acquired cystic disease, other genetic syndromes and phenocopies. Genomic testing is particularly helpful for equivocal imaging, young potential donors, atypical disease and reproductive planning.

The major disease-modifying decision is whether a suitable adult has evidence of rapid progression and can safely manage tolvaptan. The aquaretic burden affects work, sleep and access to water; hepatotoxicity monitoring is mandatory. Shared decision-making should address absolute likely benefit, daily-life burden, pregnancy, interactions and when treatment will be withheld or stopped.

Key points

ADPKD is a systemic inherited disorder causing progressive bilateral kidney cysts, hypertension, pain, haematuria, infection, stones and variable kidney failure.
Diagnosis uses age- and family-history-sensitive imaging criteria or genomic testing; simple cysts become common with age and are not equivalent to ADPKD.
Ask about intracranial aneurysm or subarachnoid haemorrhage, sudden death, kidney failure, liver cyst burden and relatives at potential reproductive risk.
Control blood pressure early and track eGFR slope, albuminuria and complications as standard kidney protection.
Risk assessment for rapid progression may use serial eGFR, height-adjusted total kidney volume, Mayo imaging class, genotype and clinical events through a specialist clinic.
NICE recommends tolvaptan for a defined adult CKD and rapid-progression population; current UKKA advice expands practical assessment but does not replace the appraisal or SmPC.
Tolvaptan causes aquaresis and carries important liver-injury risk, requiring pre-treatment testing, monthly liver tests for 18 months and three-monthly tests thereafter.
Intracranial aneurysm screening is selective and based on family history, previous aneurysm, high-risk occupation or major elective surgery and patient preference, not automatic for everyone.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Inherited pathogenic variant

A heterozygous disease-causing variant affecting polycystin biology is commonly inherited in an autosomal-dominant pattern, producing wide severity differences within and between families.

De novo or unrecognised familial disease

De novo variants, small families, early deaths or previously unrecognised mild disease can explain a compatible phenotype despite no recognised family history.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Disordered tubular signalling
Pathogenic variants, most often in PKD1 or PKD2, disrupt tubular ciliary signalling and permit progressive cyst expansion.
2
Progressive cyst expansion
Cysts enlarge throughout both kidneys, distorting normal architecture and causing pain, haematuria, infection or stone-promoting urinary stasis.
3
Compression and fibrosis
Expanding cysts compress vessels and functioning nephrons, activating inflammatory and fibrotic pathways that gradually reduce glomerular filtration.
4
Extrarenal manifestations
The disorder also causes liver cysts and is associated with intracranial aneurysm, cardiac-valve abnormalities, abdominal-wall hernia and diverticular disease.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Early hypertension

Hypertension may precede reduced eGFR and is an important modifiable driver of cardiovascular and renal risk.

Cyst haemorrhage

Abrupt flank pain with visible haematuria can follow intracystic bleeding, but persistence requires exclusion of stones, obstruction and malignancy.

Cyst infectionRed flag

Fever, inflammatory markers and focal renal or hepatic tenderness may occur even when routine urine culture is negative.

Aneurysmal haemorrhageRed flag

Thunderclap headache, meningism, collapse or focal deficit is a neurological emergency requiring the standard subarachnoid-haemorrhage pathway.

Tolvaptan toxicityRed flag

Inability to replace water losses, hypernatraemia symptoms or fatigue, anorexia, dark urine and jaundice require prompt treatment review.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Renal ultrasoundFirst step
Why
Assess bilateral cyst distribution, kidney size and alternative structural disease.
Interpretation and limitations
Apply validated age-specific criteria only in the population for which they were derived; isolated cysts in older adults have low specificity.
02
MRI total kidney volume
Why
Refine prognostic classification and rapid-progression assessment in typical morphology.
Interpretation and limitations
Height-adjusted volume and Mayo class can stratify typical disease; atypical cyst distribution requires different interpretation.
03
Serial eGFR and urine ACR
Why
Measure functional trajectory and identify additional glomerular risk.
Interpretation and limitations
Use multiple values over years where available; unusually heavy proteinuria or abrupt decline suggests a superimposed diagnosis.
04
PKD gene panel
Why
Resolve uncertain or atypical diagnosis and enable family decisions.
Interpretation and limitations
Pathogenic variants support molecular diagnosis, but negative or uncertain results require specialist phenotypic review and do not always exclude ADPKD.
05
Targeted intracranial vascular imaging
Why
Screen selected people whose aneurysm risk or consequences justify testing.
Interpretation and limitations
Use MR angiography or the local neurovascular pathway after counselling; incidental findings and repeat intervals need specialist planning.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Multiple simple renal cysts

Simple cysts increase with age but usually lack the age-sensitive bilateral burden, family pattern, renal enlargement and extrarenal features supporting ADPKD.

Acquired cystic kidney disease

Longstanding advanced kidney failure or dialysis can produce multiple cysts in small or atrophic kidneys, rather than cysts preceding decline in enlarged kidneys.

Other inherited cystic syndromes

Childhood presentation, syndromic skin or neurological findings, congenital liver disease or a recessive pedigree should prompt broader genetic assessment.

Hydronephrosis or cystic mass

Collecting-system continuity, obstruction symptoms or an enhancing complex lesion suggests dilatation or tumour rather than numerous independent simple cysts.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01DiagnoseConfirm cystic disease accuratelyFirst stepBilateral renal cysts or an affected relative raises possible ADPKD.

1Document family history, age, kidney function, blood pressure, cyst distribution and extrarenal features.
2Apply validated imaging criteria when appropriate; seek specialist radiology or genetic input for atypical morphology, absent family history or potential donation.
3Offer genetics-led cascade and reproductive counselling after confirmation, allowing at-risk adults to choose testing with informed consent.

02StratifyEstimate progression and treatment eligibilityADPKD is established in an adult with functioning kidneys.

1Calculate eGFR slope from reliable measurements and review early hypertension, urological events, genotype and family kidney-failure age.
2Use MRI total kidney volume or Mayo classification when morphology and age make it informative.
3Assess NICE tolvaptan eligibility and contraindications in a dedicated renal clinic, discussing benefit, aquaresis and monitoring feasibility.

03RespondManage cyst complicationPain, fever, haematuria or acute kidney dysfunction develops.

1Assess haemodynamic state, sepsis, urine, renal function and obstruction while considering stone, cyst haemorrhage and infection.
2Choose imaging and antimicrobial strategy with renal or microbiology advice because cyst penetration and source control matter.
3EscalationEscalate persistent bleeding, uncertain mass, obstruction or refractory pain to the appropriate urology, interventional radiology or specialist team.

04MonitorUse tolvaptan safelyA specialist initiates tolvaptan for eligible rapidly progressive ADPKD.

1Confirm baseline liver tests, hydration access, interaction review, pregnancy safeguards and understanding of expected polyuria.
2Check liver function monthly for 18 months and every three months thereafter, with kidney function reviewed on the specialist schedule.
3Withhold during acute illness or impaired water access and act promptly on possible liver injury using the live SmPC stopping rules.

Key medicines and prescribing safety2 treatments · regimens, roles and cautions

Vasopressin V2-receptor antagonism slows cyst growth and decline in renal function in selected rapidly progressive ADPKD.

Tolvaptan

Initiate and titrate only in a specialist ADPKD service for adults meeting current NICE criteria; use split dosing, interaction adjustment and stopping decisions exactly as specified by the live UKKA pathway and SmPC.

Mandatory liver tests are required before treatment, monthly for 18 months and three-monthly thereafter. Counsel about thirst, polyuria, nocturia, dehydration, hypernatraemia, CYP3A interactions, pregnancy and withholding during acute illness.

Treats the common early hypertension and provides standard proteinuric CKD protection when indicated.

ACE inhibitor or angiotensin-receptor blocker

Select one agent from the local CKD formulary and titrate to the agreed blood-pressure target with renal function and potassium monitoring.

Do not combine classes. Reassess during hypovolaemia, especially when aquaretic treatment is used, and follow pregnancy contraindications and sick-day advice.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Progressive kidney failure

Cyst expansion and interstitial fibrosis progressively remove functional nephron mass, with eGFR slope and total kidney volume helping specialist risk assessment.

Cyst bleeding and infection

Haemorrhage can cause acute pain and haematuria, while infected cysts may produce sustained fever and require specialist imaging and antimicrobial planning.

Hypertension and cardiovascular disease

Renal ischaemia and renin activation promote early hypertension, which accelerates kidney decline and adds substantial cardiovascular risk.

Stone disease

Distorted anatomy and urinary biochemical factors increase calculus formation, causing colic, haematuria, infection or obstruction episodes.

Extrarenal cysts and aneurysm

Liver cyst burden may cause pain or mass effects, while a susceptible intracranial aneurysm can rupture and cause subarachnoid haemorrhage.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Measure blood pressure, creatinine, eGFR and ACR longitudinally and document urological events that may distort short-term function.
Ask at each review about pain, visible haematuria, infection, stones, abdominal fullness and neurological red flags.
For tolvaptan, maintain the mandated liver-test calendar and document daily-life tolerability, hydration and sick-day understanding.
Review kidney-failure risk and replacement options early, including transplantation and the suitability of potential related donors.
Revisit aneurysm-screening indications when family history, occupation, planned major surgery or patient preference changes.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Family history may be absent

De novo variants, small families, early deaths and unrecognised disease can obscure dominant inheritance.

Volume predicts risk, not diagnosis alone

Total kidney volume is most useful when typical morphology and appropriate age permit validated prognostic classification.

Aquaresis is expected pharmacology

Polyuria does not itself mean toxicity, but inability to drink or emerging hypernatraemia makes treatment unsafe.

Heavy proteinuria is atypical

Marked nephrosis should trigger assessment for a superimposed glomerular lesion rather than being attributed automatically to cyst burden.

Aneurysm screening is preference-sensitive

Potential benefit must be balanced against incidental findings, anxiety and downstream intervention in an individual risk context.

11Common pitfallsFrequent interpretation and management errors.

01
Diagnosing ADPKD from a few simple cysts without considering age and family probability.
02
Using one eGFR change during infection or obstruction to label rapid genetic progression.
03
Starting tolvaptan without mandatory liver-monitoring capacity and a dehydration plan.
04
Continuing tolvaptan when oral water replacement is impossible during acute illness.
05
Screening every patient repeatedly for intracranial aneurysm without individual counselling.
06
Assuming fever and flank pain is an ordinary lower UTI despite possible cyst infection.