Cystic kidney disease refers to a group of acquired or hereditary disorders characterized by the formation of fluid-filled cysts within the kidneys. These cysts may progressively enlarge, causing structural distortion, loss of normal kidney tissue, impaired kidney function, and eventual kidney failure.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cystic kidney disorder and is a significant cause of end-stage kidney disease worldwide. It is a progressive condition with no definitive cure; however, early diagnosis, control of complications, and appropriate kidney replacement therapy can slow disease progression and improve outcomes.

Epidemiology

Autosomal dominant polycystic kidney disease is among the most common inherited kidney disorders, affecting approximately 1 in 400–1,000 individuals worldwide. It accounts for a significant proportion of patients requiring kidney replacement therapy.

The disease usually manifests in adulthood, although kidney cysts may develop years before symptoms appear. Disease progression varies between individuals and is influenced by genetic factors, blood pressure control, kidney size, and presence of complications.

Risk factors

Risk factors associated with cystic kidney disease include:

• Family history of autosomal dominant polycystic kidney disease

• Inherited mutations affecting kidney cyst formation

• Previous diagnosis of hereditary cystic kidney disease

• Hypertension

• Recurrent urinary tract infections

• Kidney stones

• Male sex and younger age at diagnosis (associated with faster progression in some patients)

• Large kidney volume at diagnosis

Pathophysiology

Cystic kidney disease results from abnormal growth and proliferation of renal tubular epithelial cells, leading to cyst formation.

In autosomal dominant polycystic kidney disease, mutations commonly occur in genes responsible for polycystin proteins, which regulate:

• Tubular cell growth

• Fluid secretion

• Cell differentiation

• Calcium signaling

Progressive enlargement of cysts causes compression and destruction of surrounding kidney tissue. This results in:

• Reduced renal blood flow

• Activation of the renin-angiotensin-aldosterone system

• Hypertension

• Progressive reduction in glomerular filtration rate (GFR)

• Chronic kidney disease and eventual kidney failure

The disease may also affect other organs, particularly the liver and cardiovascular system.

Clinical presentation

Clinical features depend on the stage of disease.

Kidney manifestations

Patients may present with:

• Nocturia

• Polyuria

• Increased urinary frequency due to impaired urine concentration ability

• Hypertension

• Flank or abdominal pain due to:

  • Cyst infection

  • Cyst bleeding

  • Kidney stones

  • Cyst rupture

  • Compression of surrounding structures

• Haematuria

• Progressive kidney dysfunction

• Uremic symptoms in advanced disease

Extra-renal manifestations

Common extra-kidney complications include:

Polycystic liver disease

• Multiple liver cysts

• Abdominal discomfort

• Enlarged liver in severe cases

Intracranial aneurysms

• Increased risk of intracranial aneurysm formation, particularly in patients with:

  • Family history of aneurysmal subarachnoid haemorrhage

  • Previous aneurysm rupture

Cardiovascular complications

• Hypertension

• Valvular heart disease, including mitral valve prolapse

Diagnostic criteria

Diagnosis is based on clinical features, family history, and imaging findings.

Ultrasonographic diagnostic criteria for autosomal dominant polycystic kidney disease

Differential diagnosis

Conditions that should be considered include:

1. Simple renal cysts

2. Acquired cystic kidney disease associated with chronic kidney disease and dialysis

3. Medullary cystic kidney disease

4. Nephronophthisis

5. Renal cystic lesions due to tuberous sclerosis complex

6. Multicystic dysplastic kidney disease

7. Renal cell carcinoma with cystic changes

8. Medullary sponge kidney

Investigations

Recommended investigations include:

Imaging

• Kidney-ureter-bladder (KUB) ultrasonography

• Contrast-enhanced computed tomography (CT) scan (higher sensitivity for detecting cyst burden and complications)

Kidney function assessment

• Serum creatinine

• Estimated glomerular filtration rate (eGFR)

Urine assessment

• Urinalysis

  • Urine biochemistry

  • Urine microscopy

Genetic evaluation

• Genetic testing for individuals considering kidney donation, especially those with a family history of cystic kidney disease

Liver function monitoring

For patients receiving tolvaptan:

• Alanine aminotransferase (ALT)

• Aspartate aminotransferase (AST)

• Bilirubin levels

Management

Management aims to:

• Slow kidney disease progression

• Control complications

• Preserve kidney function

• Manage symptoms

• Provide kidney replacement therapy when required

Non-pharmacological treatment

Recommended measures include:

Adequate fluid intake

• Increase fluid intake to more than 3 litres daily in patients without fluid retention.

• Avoid excessive fluid intake in patients with advanced kidney failure, particularly those with eGFR below 30 mL/min/1.73 m².

Blood pressure control

• Regular monitoring and treatment of hypertension.

• Cardiovascular risk reduction.

Lifestyle measures

• Maintain healthy body weight.

• Reduce dietary salt intake.

• Avoid nephrotoxic medications.

• Prompt treatment of urinary tract infections.

Kidney transplantation

Kidney transplantation should be considered in patients with end-stage kidney disease.

Some patients may require:

• Pre-transplant native nephrectomy due to:

  • Very large kidneys causing space limitation

  • Recurrent infection

  • Persistent bleeding

  • Severe pain

Pharmacological treatment

Disease-modifying therapy

Tolvaptan may be used in selected patients with rapidly progressive autosomal dominant polycystic kidney disease.

Tolvaptan (PO) 45 mg in the morning and 15 mg 8 hours later.

The dose may be increased to:

Tolvaptan (PO) 90 mg in the morning and 30 mg in the afternoon.

The afternoon dose should be taken before 4 pm.

Patients receiving tolvaptan require regular monitoring of liver function tests due to the risk of hepatotoxicity.

Management of complications

Hypertension

Management should follow chronic kidney disease and hypertension treatment guidelines.

Pain management

Treatment depends on the cause:

• Infection should be treated appropriately.

• Kidney stones should be managed according to stone management guidelines.

• Avoid unnecessary nephrotoxic analgesics.

Urinary tract infections

Prompt diagnosis and appropriate antibiotic treatment are required.

Advanced kidney disease

Patients progressing to end-stage kidney disease should be evaluated for:

• Haemodialysis

• Peritoneal dialysis

• Kidney transplantation

Referral

Referral to a nephrologist is recommended for:

• Progressive decline in kidney function

• Chronic kidney disease stage 3–5

• Rapid kidney enlargement

• Recurrent cyst infections

• Suspected intracranial aneurysm

• Preparation for kidney replacement therapy

• Assessment for kidney transplantation

Complications

Potential complications include:

• Chronic kidney disease

• End-stage kidney disease

• Hypertension

• Kidney stones

• Recurrent urinary tract infections

• Cyst infection

• Cyst bleeding

• Haematuria

• Polycystic liver disease

• Intracranial aneurysm rupture

• Cardiovascular complications

• Valvular heart disease

Prognosis

The prognosis varies depending on genetic factors, kidney size, blood pressure control, and complications.

Patients with autosomal dominant polycystic kidney disease may gradually progress to end-stage kidney disease. Early diagnosis, strict blood pressure control, appropriate monitoring, and selected use of disease-modifying therapy can delay disease progression.

Patients requiring kidney replacement therapy can achieve good outcomes with dialysis or kidney transplantation.

Prevention

Preventive strategies include:

• Screening individuals with a strong family history of cystic kidney disease

• Regular monitoring of kidney function

• Early diagnosis and treatment of hypertension

• Avoidance of nephrotoxic drugs

• Adequate hydration where appropriate

• Genetic counseling for affected families

• Careful assessment of potential living kidney donors from affected families