2. • The etiology of kidney disease not always
firmly established
• Genetic causes may be under recognised
• Non glomerular AD
• Progressive IF
• Progression to ESRD
Uromodulin (UMOD)
Renin (REN)
Hepatocyte nuclear GF(HNF1 b)
Mucin 1 (MUC1)
3. • All genes expressed in tubular cells of the
intermediate or distal nephron
• UMOD : TAL
• UMOD/MUC/REN: confined to kidney
• HNF 1B : Extra-renal
4.
5. • KDIGO consensus conference : Terminology
• Genetic cause & inheritance pattern
• Phenotypic confirmity of a disease by 4
different genes
• Differentiate from other AD of tubular origin
• Avoids misnomers
• Simple and easy to use
6. Clinical features
• Family history
• Progressive loss of kidney function
• Bland urinary sediment
• Absent or mild proteinuria
• No severe hypertension : early stages
• Nocturia
• Normal sized kidneys
7. Histology
• IFTA
• Normal glomeruli
• Thickening and lamellation of tubular BM
• Tubular dilatation and microcysts
• IF : negative
• Electron microscopy
8.
9. Gene defect and pathophysiology
UMOD
• Uromodulin
• Mutant uromodulin in the ER of TAL
• Decreased urinary excretion of uromodulin
• Trafficking of NKCC2 to the luminal side affected
• Proximal reabsorption of uric acid
10. MUC1
• Mucin 1
• Highly glycosylated transmembrane protein
expressed throughout the distal nephron
• Luminal epithelial mucobarrier
• Frameshift mutation : mucin fs
11. HNF1B
• Regulate multiple gene kidney ,pancreas , liver
• Regulate the UMOD gene
• Several genes involved in PCKD
REN
• Encodes prepro renin
• Apoptosis of the renin producing cells
12. • Diagnostic criteria for ADTKD
• Family h/s/o AD inheritance
• Compatible histology in one family member
• Demonstration of the mutant gene in affected
individual or atleast one of the family member.
13. Follow up & treatment
• Control of risk factors
• Regular monitoring of renal function
• General CKD guidelines
• ? ACE; losartan : in those with hyperuricemia
• UMOD :
– Allopurinol/ febuxostat
– Low purine diet
14. • Diuretic : cautious
• Liberal water intake
• Low salt not preferred in UMOD and REN
• Avoid NSAID
• EPO and Fludrocortisone in REN
• Kidney transplantation
16. 21/06/2017 – RIF RT
•External iliac artery tortuous but otherwise normal.
•Normal anatomy of ext. iliac vein
•Normal anatomy of internal iliac, and common iliac
arteries and vein
•No evidence of any arterial calcification / narrowing.
•Bladder Normal in appearance and wall thickness.
•Warm Ischemia Time - 3.0 minutes 53 sec.
•Cold Ischemia time 1 hour 47minutes
18. 22/06/2017 - Re-exploration
•Graft kidney bluish and turgid, not bleeding on
pricking with a needle, renal vein thrombosis
present , normal pulsation in renal artery.
•Ureter and pelvis fully packed with thrombus.
Periureteral vessels thrombosed.Ureter looked
non viable.
•Warm Ischemia Time – 5 min minutes.
•Cold Ischemia time ~ 2½ hours
