Autosomal dominant polycystic kidney disease (APKD)
- Variety of inherited conditions affecting kidney – but adult polycystic kidney disease (APKD) is most common
- Accounts for 8-10% of patients with end stage renal failure
- Autosomal dominant inheritance: chromosome 16 (PKD1 gene in 95% of cases), or C14 PKD2 in 5%.
- Typically presents in adulthood
- Characterised by progressive appearance and enlarging renal cysts – these may bleed, become infected. As cysts enlarge – renal function deteriorates. Patients may present with abdo masses, HTN (>75%), MVP (>25%), chronic renal failure, SAH in 10% due to associated beri aneurysms!!!
- Cysts can also occur in liver, pancreas, spleen, ovaries.
- Ix: USS, CT, renal function by serum creatinine and creatinine clearance. Exclude UTI.
- Mx: control HTN, if infection = Abx, if pain = analgesia, as disease progresses = dialysis, then finally transplant. Genetic counselling is important in >18yo’s.
- Occur with ageing – >12% of popn >50yo will have cyst(s).
- Usually asymptomatic and detected incidentally
- Important to distinguish from multiple cysts of APKD, other cystic diseases and renal cell carcinoma
- On USS = smooth walls and no intracystic debris. If doubt = CT scan.
- Haematuria, sensorineural deafness (overt in 40%), progressive renal impairment with proteinuria and eye/ocular abnormalities in 15%
- Caused by mutation in basement membrane type IV collagen gene (=COL4A5).
- X-linked in 80% (=creating a more severe phenotype in men)
- Ix: renal biopsy = thickening and splitting of glomerular basement membrane on electron microscopy
- End stage renal failure (ie disease requiring dialsysis) develops between 16-35 years of age in virtually all males with X-linked Alport’s syndrome.
- Mx: transplantation can result in a Goodpastures disease-like syndrome caused by the immunological reaction to the unseen type IV collagen from the transplanted kidney
Medullary sponge kidney:
- Dilated medullary collecting ducts and can affect both or just one kidney
- Small calculi can form resulting in haematuria and predispose to UTI/obstruction.
- Ix: Intravenous urogram (IVU) = shows a ‘blush-like’ opacity in medulla corresponding to accumulation of contrast in dilated collecting ducts
- Rare (1/100,000), autosomal dominant
- Tumour like malformations (=hamartomas) develop in CNS (=learning disorders and epilepsy) and also skin lesions including facial angiofibromas and hypomelanotic macules and kidneys can develop angiomyolipomas, cysts and malignancies.
Von Hippel-Lindau syndrome
- Very rare, autosomal dominant
- Tumours affecting kidneys (=renal cell carcinoma), brain (=haemangioblastomas), adrenals (=phaechromocytoma)
- Mutations in VHL gene also seen in patients with sporadic renal cell carcimonas
- X-linked recessive
- Mutations to gene encoding alpha-galactosidase A (=accumulation of intracellular glycosphinolipids) = progressive renal failure, autonomic dysfunction and skin lesions (=’angiokeratomas’ = dark red macules).
- Diagnosis confirmed by reduced urinary alpha-galactosidase A