ADPKD (AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE)

·         AD

·         Most common hereditary human kidney disease.

·         Adults (onset- 4^th – 5^th decade)

·         Mutations in-

o   PKD-1 (16p13)- polycystin-1 (ADPKD-1) [transmembrane glycoprotein receptor]

o   PKD-2 (4q21)- polycystin-2 (ADPKD-2) [nonselective cation channel]

• Pathogenesis-

·         Pathology

o   Kidneys are enlarged & have cortical & medullary cysts

·         Features-

o   Abdominal discomfort & pain, due to:-

§  Mass effect of enlarged kidneys

§  Cyst rupture/ Hemorrhage into cyst

o   Hematuria- (gross/microscopic)

§  Cyst rupture into collecting system

§  Uric acid/calcium oxalate stones

o   Nephrolithiasis- 20% cases

o   Urinary tract infection

o   Infection of kidney/liver cyst-

§  Most common due to Gram –ve bacteria

§  Blood cultures +ve, but urine culture may be –ve (because the infected cysts usually do not communicate with collecting system)

o   Hypertension

§  Common & usually precedes renal dysfunction.

o   Progressive renal dysfunction with ESRD after 10-20 yrs

§  Risk factors

·         Younger age at diagnosis

·         Black race

·         Males

·         ADPKD-1

·         Hypertension

o   Extra-renal manifestations

§  Intracranial aneurysms (usually of anterior cerebral circulation)

·         ↑ risk of rupture

§  Aortic root/annulus dilatation (Aortic Regurgitation)

§  Mitral valve prolapse

§  Hepatic cysts (40%)-

·         May bleed/rupture/become infected

·         Though incidence in Male = Female , but Females have larger cysts

§  Colonic diverticulae

·         Diagnosis-

o   Renal USG- ‘Enlarged kidneys with multiple bilateral macrocysts’

§  100% sensitivity in subjects > 30 yrs.

o   CT scan or T2-weighted MRI- most sensitive in subjects < 30 yrs.

o   Linkage analysis & mutational screening

o   Criteria for diagnosis-

§  In young subjects- ≥2 cysts in one kidney & ≥1 cyst in contralateral kidney

§  In older subjects >60 yrs- ≥4 cysts in kidney

§  Presence of positive family history

·         Treatment-

o   Mainly supportive

§  Control hypertension [aim- ≤ 130/85 mm Hg as per JNC VII guidelines]

§  Inhibit rennin-angiotensin system

§  Lipid-soluble antibiotics (e.g.trimethoprim-sulfamethoxazole, quinolone antibiotics) preferred for infected kidney & liver cysts