Inherited Kidney Disease Flashcards
(47 cards)
what is the cause of ADPD?
mutation in PKD gene 1 and PKD gene 2
where do the cysts in ADPD arise from?
from renal tubular epithelium in both cortex and medulla
what do PKD-1 and PKD-2 code for?
polycystin 1 and 2 proteins
what is the role of polycystin 1 and 2 proteins?
Components of primary cillia= appendages that stick out from cells and receives developmentally important signals – when filtrate flows through nephron cillia bend allowing influx of calcium which activates pathway of cell inhibition of proliferation
what is the pathophysiology of ADPD?
absence of component of primary prevents inhibition of cell proliferation - cells to continue to proliferate abnormally – expresses proteins that allow water to enter lumen of cyst – grow in size
what are the renal clinical features of ADPD?
recued urine concentration ability, renal enlargement, chronic flank pain, hypertension, haematuria (cyst rupture, cystitis, stones), cyst infection, renal failure
what are the extra renal clinical features of ADPD?
o Hepatic cysts – function preserved, result in SOB, pain, ankle swelling
o Intracranial – anterior circulation (Berry aneurysms)
o Cardiac – mitral/aortic valve prolapse
o Collagenous degeneration (aortic root dilation)
o Diverticular
o Hernias
o Ovarian cysts
how is ADPD diagnosed?
- Radiological – US
* Genetic - linkage and mutation analysis
what is the criteria for ADPD?
o Age 18-39, >3 unilateral or bilateral cysts
o Age 40-59, >2 cycts in each kidney
o Age >60, >4 cysts in each kidney
what is the management of ADPD?
Counselling Hypertension control Hydration Tolvaptan Dialysis + Transplant
what are the indications for tolvaptin in ADPD management?
CKD 2 or 3, rapidly progressing, discount agreed
What is the cause of ARKD?
mutation of PKDH1 on chromosome 6
what are the clinical features of ARKD?
- Palpable kidneys
- Hypertension
- Recurrent UTIs
- Slow decline in GFR
what does PKDH1 code for?
fibrocystin
what is the pathophysiology of ARKD?
similar to ADPKD
where do the ducts in ARK arise from?
collecting duct system
what is the cause of Alports Disease?
mutation of COL4A5 (X linked inheritance), also COL4A3, COL4A4
what is the underlying mechanism of alports disease?
Disorder of Type 4 collagen
what is the structure of collagen?
o Sheet like structure composed of tightly packed heterotrimers (made of 3 alpha chains composed of Alpha 3/Alpha 4/Alpha)
what is the consequence of Alports Disease on collagen?
o Mutations mean glycine molecule is replaced with larger molecule – can’t pack tightly
what is the pathophysiology of Alports Disease?
- Missing or non function collagen IV causes GBM to become thin + more porous
- Allows red blood cells to pass (haematuria) – proteins are able to pass through (proteinuria) – GBM undergoes sclerosis – renal failure + hypertension
what are the clinical features of alports?
Haematuria – (microscopic, then macroscopic + proteinuria)
Raised BP
Sensorineural deafness
Anterior lenticonus
what is the histology features of Alports disease?
variable thickened GBM with splitting, basket weave
what is the management of Alports Disease?
no specific treatment
standard aggressive treatment of BP, proteinuria
Dialysis/Transplantation
