Autosomal dominant polycystic kidney disease is a hereditary condition affecting adults characterised by bilateral, multiple renal cysts with hallmark mutations in PKD1 or PKD2 genes.
Description
ADPKD is a genetic disorder characterised by the development of numerous fluid-filled cysts in the kidneys. It’s one of the most common hereditary kidney diseases, with significant morbidity and mortality, often leading to end-stage renal disease (ESRD).
Pathogenesis
ADPKD is an inherited condition, primarily associated with mutations in two genes: PKD1 (located on chromosome 16) and PKD2 (on chromosome 4). Mutations in these genes result in abnormal proteins polycystin-1 and polycystin-2, respectively, leading to the development and growth of renal cysts.
PKD1 mutations generally cause a more severe phenotype with an earlier onset of ESRD compared to PKD2 mutations.
Epidemiology, Risk Factors & Associations
- Prevalence: ~1 in 400-1,000 live births (1).
- Both males and females are equally affected.
- Mutations in the PKD1 gene are responsible for the majority of cases (approximately 85%), with the remaining linked to PKD2 gene mutations.
- Certain mutations are associated with more severe disease and earlier onset of ESRD.
- Associated with saccular cerebral aneurysms.
Clinical Features
- Hypertension: Common and usually occurs before loss of kidney function.
- Flank pain, haematuria, recurrent urinary tract infections, and kidney stones.
- Renal failure: Occurs typically in the fifth or sixth decade with PKD1 and a decade later with PKD2.
- Extrarenal manifestations include hepatic and pancreatic cysts, intracranial aneurysms, and cardiac valve abnormalities.
Complications
- Chronic kidney disease (CKD) and ESRD: Most significant complications of ADPKD.
- Sacculary (berry) aneurysms: Occur in 8-12% of individuals.
- Cardiovascular complications: Mitral valve prolapse, left ventricular hypertrophy.
- The risk for renal cell carcinoma is not increased in comparison with the general population except in patients on dialysis
- Cyst complications include haemorrhage, pyogenic infection, and, more rarely, rupture.
Pathological Features
Histopathology
- Numerous cysts varying in size from a few millimeters to several centimeters.
- The cysts progressively replace the normal renal parenchyma.
Serology
- Elevation in serum creatinine and blood urea nitrogen (BUN) as kidney function declines.
Genetics
- Autosomal dominant inheritance with high penetrance
- Mutations in the PKD1 or PKD2 genes.
Radiological Features
General Features
- Typically bilateral, affecting both cortical and medullary regions. Rarely, the disease can present asymmetrically, segmentally, or unilaterally.
- Typically enlarged kidneys, filled and replaced by numerous cysts. The presence of more than 10 renal cysts is diagnostic in patients at risk for ADPKD.
- Kidneys can become exceptionally large (> 20 cm), extending into the pelvis.
- Little recognisable renal parenchyma is present at the end stage.
US
- Cysts range from simple (anechoic) to complex (hyperechoic content, thick wall, septations).
- Diagnostic criteria based on ultrasound findings (Pei-Ravine criteria) help determine the likelihood of ADPKD in at-risk individuals or those with a family history.
CT
- Cysts may be simple, with water attenuation (0-20 HU), and imperceptible walls, with no enhancement on contrast-enhanced CT (CECT).
- Complicated cysts, such as hemorrhagic or infected cysts, display different characteristics. Haemorrhagic cysts have hyperdense content (≥ 70 HU), with or without mural calcifications. Infected cysts may have thick, irregular walls, with or without gas, and possible wall enhancement.
MRI
- Simple cysts demonstrate high signal intensity on T2 and low signal intensity on T1 MRI.
- Complicated cysts show high signal intensity on T1 and variable signal intensity on T2 MRI, with no enhancement on contrast-enhanced images.
Grading and Staging
- ADPKD is not typically graded or staged.
- Disease progression can be monitored by measuring total kidney volume (TKV) and estimated glomerular filtration rate (eGFR).
- A TKV of more than 600 ml or a growth rate of more than 5% per year is predictive of a more rapid progression to ESRD.
Differential Diagnosis
- Autosomal recessive polycystic kidney disease (ARPKD): Presents in infancy or childhood.
- Medullary cystic kidney disease: Cysts limited to the medulla.
- Simple renal cysts: Typically unilocular and asymptomatic.
Management
ADPKD requires careful management due to its high risk of leading to ESRD and its associated extrarenal manifestations. The disease is typically managed by a nephrologist, sometimes in conjunction with a geneticist for family planning and genetic counselling purposes. Regular monitoring of renal function, blood pressure, and potentially intracranial imaging for aneurysm detection in those with a family history, are crucial components of management.