Autosomal dominant polycystic kidney disease
- Lesion
Inherited defects in polycystin proteins make tubules swell into countless cysts that enlarge the kidneys and destroy them over decades.
What it is
ADPKD is one of the commonest inherited diseases and a significant cause of kidney failure. PKD1 (polycystin-1) causes most cases and more severe disease than PKD2 (polycystin-2). Polycystins in the primary cilium sense urine flow and control calcium entry; their loss raises cyclic AMP and drives cell proliferation and fluid secretion. Cysts start in all nephron segments but form in only a small fraction of nephrons, because a second somatic hit is needed in each. It has also been studied in Colombian families (see the sources).
Structure
- Kidneys may weigh several times normal; the surface is a mass of cysts, with remaining parenchyma between them.
- Cysts are lined by cuboidal or flattened epithelium, sometimes papillary; some contain blood or calcified material.
- Interstitial fibrosis and compression atrophy of the remaining nephrons.
- The liver shows cysts derived from bile ducts; brain arteries can show saccular aneurysms.
Step by step
- Each cell carries one inherited faulty PKD1 or PKD2 allele.
- In a few tubular cells, a second hit inactivates the other allele.
- Without polycystin signalling, the cilium cannot sense flow and intracellular calcium falls.
- Cyclic AMP rises, cells proliferate and secrete chloride and fluid into the lumen.
- The segment balloons and detaches from the nephron as a closed cyst.
- Thousands of enlarging cysts compress the remaining kidney and cause fibrosis and kidney failure.
Clinical notes
- Kidney failure usually develops between the fourth and sixth decades, earlier with PKD1.
- Screening for intracranial aneurysms is considered for patients with a family history of hemorrhage.
- Cyst hemorrhage and infection cause acute pain; stones (often uric acid) are common.
Test yourself
Think of the answer, then tap the question to see it.
Which gene accounts for most ADPKD and the more severe form?
PKD1, which encodes polycystin-1.
Why do cysts form in only some nephrons when every cell carries the mutation?
A second, somatic hit inactivating the normal allele is needed in each cyst-forming cell.
Which extrarenal lesion can cause sudden death in ADPKD?
A ruptured berry aneurysm of the circle of Willis, giving subarachnoid hemorrhage.
Elsewhere in DurgiPedia
- Multicystic dysplastic kidney and polycystic kidney disease
- Mendelian inheritance: autosomal dominant, recessive and X-linked
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Autosomal Dominant Polycystic Kidney Disease (StatPearls (NCBI Bookshelf), 2024); Autosomal dominant polycystic kidney disease in Colombia (BMC nephrology, 2023).
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Representative model, for educational purposes only.