Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder — affecting approximately 12.5 million people globally. Caused by mutations in PKD1 (approximately 75%) or PKD2 (approximately 15%) genes, it causes gradual growth of fluid-filled cysts in both kidneys — progressively replacing functional kidney tissue. Most patients are diagnosed in their 30s-40s when kidney enlargement, hypertension or cysts in other organs prompt investigation. ADPKD is the 4th or 5th most common cause of end-stage kidney disease requiring dialysis or transplantation in high-income countries.

How does ADPKD progress?

ADPKD is typically slowly progressive over decades. Kidneys grow gradually (normal kidneys are approximately 150-250mL; severely affected ADPKD kidneys can reach 5-10 litres per kidney). GFR remains normal until cysts replace >70% of parenchymal volume — typically in the 5th-7th decade. PKD1 patients progress faster (ESKD approximately 55-65 years) than PKD2 patients (ESKD approximately 70-75 years). Rapid progressors (Mayo Class C-E): eGFR decline exceeding -5 mL/min/year — these benefit most from tolvaptan.

What is tolvaptan and how does it work?

Tolvaptan (Jynarque in the US) blocks vasopressin V2 receptors in kidney collecting duct cells — preventing vasopressin-stimulated cAMP production that drives cyst epithelial cell proliferation and fluid secretion into cysts. The TEMPO 3:4 trial (3 years, PKD1 patients): tolvaptan reduced total kidney volume growth by approximately 50% and slowed eGFR decline by approximately 30% compared to placebo. FDA approved tolvaptan for ADPKD in 2018. Major limitation: hepatotoxicity risk (approximately 1% serious liver injury) — requires monthly liver enzyme monitoring. Side effects of vasopressin antagonism: polyuria, polydipsia, nocturia (patients need to drink 3-4 litres/day).

What are the extrarenal manifestations?

ADPKD affects multiple organs: Intracranial aneurysms (ICAs): approximately 8-12% of patients — risk of rupture causing subarachnoid haemorrhage. Screening by MR angiography recommended in those with family history of aneurysm rupture or high-risk occupations. Liver cysts: very common (approximately 80% by age 60); usually asymptomatic but can cause severe pain, infection or mass effect in extreme cases. Pancreatic cysts; seminal vesicle cysts; abdominal wall and inguinal hernias; cardiovascular (hypertension, mitral valve prolapse, dilatation of the aortic root).

How is blood pressure managed in ADPKD?

Hypertension affects approximately 50-70% of ADPKD patients, often beginning before renal impairment is measurable. The renin-angiotensin system (RAS) is pathologically activated by intrarenal cyst compression of normal tubules. ACE inhibitors or ARBs are first-line antihypertensives and may additionally slow cyst growth (HALT-PKD trial — particularly effective combination in younger patients). Target blood pressure: <130/80 mmHg (KDIGO) or <110/75 in young patients with preserved GFR and large kidneys (HALT-PKD: intensive BP control slowed kidney growth in early ADPKD).

Is there a cure for ADPKD?

No cure — management is disease-modifying (slowing progression) and supportive. Tolvaptan is the only approved disease-modifying treatment. Research pipeline: other mTOR inhibitors, tyrosine kinase inhibitors, CDK inhibitors, and gene therapy approaches are in development. Kidney transplantation is curative for ESKD — ADPKD patients have excellent transplant outcomes and do not experience recurrence in the transplanted kidney (as cysts arise from the host's own kidney cells). Native kidney nephrectomy may be required for very large kidneys causing abdominal symptoms or to create space.

Should first-degree relatives be screened?

Yes — ADPKD is autosomal dominant with high penetrance; each first-degree relative of an ADPKD patient has a 50% risk of carrying the mutation. Ultrasound screening detects most ADPKD by age 30 (sensitivity approximately 95%). Genetic testing (PKD1/PKD2 sequencing) can identify mutation before ultrasound changes are apparent — relevant for living kidney donors (who must be excluded if they carry the mutation). There are no universal screening guidelines — practice varies by country. Diagnosis allows early blood pressure control and lifestyle modification.

How does GMJ News cover ADPKD?

GMJ News covers WHO ADPKD data, tolvaptan TEMPO trial evidence, total kidney volume biomarker, intracranial aneurysm screening, blood pressure management and the ADPKD research pipeline. ADPKD is a significant hereditary kidney disease in Georgia — directly relevant to PHIG's nephrology programme and the Georgian Medical Journal.

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Autosomal Dominant Polycystic Kidney Disease

Q: Is there a cure for ADPKD?

No cure — management is disease-modifying (slowing progression) and supportive. Tolvaptan is the only approved disease-modifying treatment. Research pipeline: other mTOR inhibitors, tyrosine kinase inhibitors, CDK inhibitors, and gene therapy approaches are in development. Kidney transplantation is curative for ESKD — ADPKD patients have excellent transplant outcomes and do not experience recurrence in the transplanted kidney (as cysts arise from the host's own kidney cells). Native kidney nephrectomy may be required for very large kidneys causing abdominal symptoms or to create space.

Q: Should first-degree relatives be screened?

Yes — ADPKD is autosomal dominant with high penetrance; each first-degree relative of an ADPKD patient has a 50% risk of carrying the mutation. Ultrasound screening detects most ADPKD by age 30 (sensitivity approximately 95%). Genetic testing (PKD1/PKD2 sequencing) can identify mutation before ultrasound changes are apparent — relevant for living kidney donors (who must be excluded if they carry the mutation). There are no universal screening guidelines — practice varies by country. Diagnosis allows early blood pressure control and lifestyle modification.

Q: How does GMJ News cover ADPKD?

GMJ News covers WHO ADPKD data, tolvaptan TEMPO trial evidence, total kidney volume biomarker, intracranial aneurysm screening, blood pressure management and the ADPKD research pipeline. ADPKD is a significant hereditary kidney disease in Georgia — directly relevant to PHIG's nephrology programme and the Georgian Medical Journal.

GMJ News knowledge hub · last reviewed September 2026 · Georgian Medical Journal

Summary Statistics Glossary GMJ news FAQ Documents Organizations Research

Autosomal dominant polycystic kidney disease (ADPKD) — the most common hereditary kidney disorder — affects approximately 12.5 million people worldwide (1 in 400-1,000 births), caused by mutations in PKD1 (approximately 75%) or PKD2 (approximately 15%) genes encoding polycystin proteins essential for tubular cell proliferation control (WHO). Progressive bilateral renal cyst enlargement leads to end-stage kidney disease in approximately 50% of patients by ages 55-65 (PKD1) or later (PKD2). Tolvaptan (TEMPO 3:4 trial) — the first approved disease-modifying treatment for ADPKD — slows cyst growth and preserves kidney function, though its hepatotoxicity requires monitoring and limits use.

Key messages

12.5 million people — most common hereditary kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) affects approximately 12.5 million people worldwide (1 in 400-1,000 births) — the most common hereditary kidney disease, caused by mutations in PKD1 or PKD2 genes (WHO).

Progressive kidney failure

ADPKD causes progressive bilateral kidney cyst enlargement leading to end-stage kidney disease (ESKD) requiring dialysis or transplantation in approximately 50% of PKD1 patients by age 55-65 years (PKD2 patients progress more slowly).

Tolvaptan — first approved disease-modifying treatment

Tolvaptan (Jynarque/Samsca) — a vasopressin V2 receptor antagonist — is the first approved disease-modifying treatment for ADPKD. The TEMPO 3:4 trial showed tolvaptan significantly slows kidney growth and eGFR decline at the cost of hepatotoxicity risk requiring monitoring.

Total kidney volume — the biomarker

Total kidney volume (TKV) measured by MRI is the primary biomarker of disease progression in ADPKD — used to identify rapidly progressing patients who benefit most from tolvaptan. The Mayo Clinic Imaging Classification guides treatment eligibility.

Extrarenal manifestations

ADPKD affects multiple organs: intracranial aneurysms (in approximately 8-12% — rupture risk); hepatic cysts (very common, usually benign); pancreatic cysts; cardiovascular (hypertension, mitral valve prolapse); seminal vesicle cysts; abdominal wall hernias.

Blood pressure control is critical

Hypertension — affecting approximately 50-70% of ADPKD patients, often before renal impairment develops — accelerates cyst growth and kidney function decline. ACE inhibitors or ARBs are first-line (renin-angiotensin system activation is a pathogenic driver).

Key statistics

~12.5M

people with ADPKD globally

WHO

1 in 400-1,000

live births affected

WHO

~50%

of PKD1 patients reach ESKD by ages 55-65

ERA/KDIGO

8-12%

have intracranial aneurysms (rupture risk)

WHO

2014

year tolvaptan FDA/EMA approval for ADPKD

FDA/EMA

5th

most common cause of ESKD in many HICs

ERA/USRDS

ADPKD kidney function decline by genotype — eGFR trajectory

Source: Published longitudinal ADPKD cohort data. PKD1 truncating mutations have the fastest progression.

Glossary of key terms

PKD1 and PKD2
WHOThe two main ADPKD genes: PKD1 (chromosome 16) — encodes polycystin-1; accounts for approximately 75-80% of ADPKD; faster progression to ESKD. PKD2 (chromosome 4) — encodes polycystin-2; approximately 15% of ADPKD; slower progression (ESKD approximately 10-15 years later than PKD1). Polycystins are involved in mechanosensory signalling in tubular epithelial cells.

Tolvaptan (Jynarque/Samsca)
FDA 2018/EMAA selective vasopressin V2 receptor antagonist — blocks vasopressin-stimulated cAMP production in tubular cells, which drives cyst growth. TEMPO 3:4 trial (3 years): tolvaptan slowed total kidney volume growth by approximately 50% and eGFR decline by approximately 30%. Limitations: hepatotoxicity (1% risk serious liver injury — requires monitoring); aquaretic side effects (polyuria, polydipsia, nocturia); not recommended in advanced CKD (eGFR <25 mL/min).

Total kidney volume (TKV)
KDIGO/ERAThe primary imaging biomarker for ADPKD progression — measured by MRI. Normal kidneys are approximately 150-250mL; severely affected ADPKD kidneys can reach several litres. Mayo Clinic Imaging Classification (MIC) uses age-adjusted TKV to classify patients as A (average risk) to E (rapid progression) — used to guide tolvaptan eligibility.

Intracranial aneurysm (ICA) in ADPKD
WHOApproximately 8-12% of ADPKD patients have intracranial aneurysms (vs approximately 2-3% general population) — most commonly in the anterior communicating and internal carotid arteries. Risk of rupture depends on size, location and family history. Screening MRA is recommended for ADPKD patients with family history of aneurysm rupture or high-risk occupations.

mTOR inhibitors in ADPKD
ResearchmTOR pathway activation promotes cyst growth. mTOR inhibitors (sirolimus, everolimus) reduced cyst growth in animal models but disappointing Phase 3 results — only modest effects on kidney volume and no benefit on eGFR decline. Not currently recommended for ADPKD outside trials.

ARPKD (autosomal recessive PKD)
WHOA distinct, far rarer condition (1 in 20,000) — PKHD1 gene; presents in infancy with severe bilateral kidney enlargement, renal failure and portal hypertension. Distinguished from ADPKD by age of presentation and inheritance pattern.

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Autosomal Dominant Polycystic Kidney Disease

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