Flashcards in Week 4: inherited and cystic renal diseases Deck (10):
Autosomal polycystic kidney disease (ADPKD). What are the genotypes?
-PKD1 on Chrom 16: 90% of disease in white Europeans. product of PKD1 is polycystin 1-invoked in matrix protein interaction
-PKD2 gene on chromosome 4: 10% of ADPKD- polycystin 2 is product
-each child had 50% chance of having the defective gene
How do you diagnose ADPKD?
-suspect in those with affected family members
-gene linkage analysis
-Ultrasonography for cysts: up to 20% of patients with PKD1 will have normal study before age 30
-symptoms begin by 20s and 30s
-most common: flank pain, hematuria (50%), symptoms seen in HTN
-80-100% have inability to concentrate urine
How do cysts form in ADPKD? Pathogenesis.
-cyst fomartions begins in urtero w/ local dilatation of renal tubule-->cell proliferation with time-->epithelial secretory activity that pumps fluid into cyst space
-only a minority of nephrons develop cysts: two hit hypothesis-somatic mutation of normal PKD1 allele in one tubular cell provides second hit
-->monoclonal proliferation leading to cyst formation
-fluid accumulation: transfer of chloride into lumen mediated by basolateral NK2Cl and CFTR in apical side
-abnormal signaling: up regulation of mTOR-->increased cAMP-->increased Cl- through CFTR
Physical exam findings in ADPKD
-enlarged irregular kidneys are palpable
-urine: leukocytes, RBCs,
Extra-renal manifestations of ADPKD
-hepatic cysts >50% of patients
-congenital hepatic fibrosis- rare
-cardiac valvular abnormalities
-other organ cysts
Renal complications of ADPKD in adults.
-hematuria, hmorrhage or both
-acute and chronic pain
Define Alport's syndrome.
-inherited kidney disease with proteinuria, hematuria, and deafness
-x linked dominant, mutations in COL4A5 gene that encodes alpha-chain of type IV collagen
-develop ESRD, treated by hemodialysis or transplant
Pathogenesis of Alport's syndrome.
-6 alpha chains that make type 4 glomerular collagen
-embryo: 1 and 2 chain
-immature state: 3,4,5 and 5,5,6
-mature: 3,4,5 and 1,1,2 and 5,5,6
-in alport's syndrome, don't have normal structural organization because of mutation in alpha 3,4, or 5
diagnosis of Alport's syndrome.
-family hx of nephritis, hematuria,
-persistant hematuria without another nephropathy
-bilateral hearing loss of high pitches
-mutation in COL4A(3,4,5)
-lack of Alport epitope in immunohistochemical
-GBM thickening, thinning, and splitting
-ocular lesions: lenticonus, posterior capsular cataract, retinal flecks
-gradual progression to ESRD in at least 2 family members