Genetic kidney disease Flashcards
(23 cards)
What is a cyst?
A sac like structure containing fluid
Where do cysts in the kidney arise from?
Renal tubules
how do cysts in the kidneys cause problems?
- compressing other structures
- Replacing useful tissue
- Bleeding
- Pain
What is the most common inherited kidney disorder?
Autosomal dominant/adult polycystic kidney disease
What are the gene mutations underlying PKD and what is the distribution of the mutations?
- PKD 1: 85%
* PKD 2: 15%
What are polycystins?
- Located in renal tubular epithelia and in the liver and pancreas ducts
- They are membrane proteins involved in intracellular calcium regulation
What are the renal complications of ADPKD?
- 50% risk of ESRD by age 50 (PKD 1 tends to have a more severe phenotype than PKD 2)
- Cyst accidents: haemorrhage, infection, rupture
What are the non renal complications of ADPKD?
- Hypertension
- Intracranial aneurysm
- Mitral valve prolapse
- Aortic incompetence
- Colonic diverticular disease
- Liver/pancreas cysts
- Hernia
Describe the natural history of adult PKD
- Age 20-30 cysts become visible
- Age 30-40 kidney size increases and eGFR begins to fall
- Age 40-70 end stage kidney disease develops (PKD2 slightly later than PKD1)
Explain the diagnosis of ADPKD
•Ultrasound: ADPKD is associated with cysts at an early age, diagnose if there is a family history and:
- 2+ cysts age 15-30
- 2+ cysts in each kidney 30-59
- 4+ cysts in each kidney age 60+
- if no family history then 10 or more cysts in both kidneys, renal enlargement or liver cysts
•CT or MRI are more sensitive
What is the screening programme for ADPKD?
- If suspected/family history
- Ultrasound at age 21
- If negative should be repeated at age 30
What is the management of ADPKD?
•Supportive
•Blood pressure lowering
•Cysts events managed appropriately:
- infection : antibiotics and drainage if required
- haemorrhage: analgesia, transfusion
•Management of extra-renal associations
•kidney replacement therapy for ESKD
•Tolvaptan: vasopressin V2 receptor antagonist
What are the side effects of tolvaptan?
- Liver toxicity
* Polyuria
What is Von Hippel Lindau?
•Autosomal dominant cystic kidney disease •Multiple benign and malignant tumours - renal cell carcinoma - benign tumours in pancreas - pheochromocytoma
What is tuberous sclerosis?
- Autosomal dominant cystic kidney disease
- Multiple benign tumours in brain, eyes, kidney, heart and skin
- Associated with epilepsy and learning difficulties
- Kidney cysts and angiolyomyolipoma (renal tumour)
What is autosomal recessive polycystic kidney disease?
- Manifests in early childhood
* Hepatic fibrosis and liver failure and renal failure
What is medullary cystic kidney disease
- Autosomal dominant
- Can have normal kidney function
- Small to normal size kidneys
- Can be associated with gout
What is Alport’s syndrome?
- X linked inherited kidney disorder
- Alpha 3, 4 or 5 gene mutation
- Deafness and renal failure
- 90% on dialysis or transplant by 40, 50% by 25
- Sensorineural hearing loss late childhood
- Impaired assembly of collagen
Describe Alport’s syndrome on EM
Abnormally split and laminated glomerular basement membrane
What are the clinical signs of Alport’s syndrome?
•Microscopic haematuria, proteinuria and end stage renal failure
What is Fabry’s disease?
- X linked storage disorder
- Alpha galactosidase A deficiency resulting in accumulation of globotriaosylceramide (Gb3)
- GB3 accumulates in the glomeruli, particularly podocytes causing proteinuria and ESRF
- Also causes neuropathy, cardiac and skin features
How do you diagnose Fabry’s disease?
- Measure alpha gal A activity in leukocytes
* Renal biopsy- inclusion bodies of G3b
What is the management of Fabry’s disease?
Enzyme replacement therapy
