Autosomal Dominant PKD (ADPKD)

Etiology and Pathogenesis

Clinical Manifestations

Renal Manifestations

Cardiac Manifestations

Extra-Renal Manifestations

• Liver cysts derived from biliary epithelia are the most common. This is different than AD polycystic liver disease which does not progress to renal failure. Massive polycystic liver disease occurs almost exclusively in women, especially those with multiple pregnancies.
• Intracranial aneurysms occur 4-5x more commonly in ADPKD than normal. Due to defects in arterial SM cells. FHx of ICA is a risk factor for rupture. Screening might be considered via MR angio for pre-symptomatic ADPKD patients with a history of ICA
• Other vascular abnormalities
  • Diffuse arterial dolichoectasias of the A/P cerebral circulation, predisposing to arterial dissection and stroke
  • MV prolapse (30%)
  • TV prolapse
  • Other valvular insufficiencies
• Colonic diverticulae
• Abdominal wall hernias

Management of ADPKD

There is no widely used specific treatment to prevent cyst growth or renal function decline.

Blood Pressure

• Classic targets are <130/80 mmHg, with an ACE/ARB. Consider SBP target < 120 mmHg as per newest 2021 KDIGO guidelines
• In HALT-PKD (NEJM 2014), a target of 95/60 to 110/75 mmHg slowed kidney growth, reduced albuminuria compared to a conservative target of 120/70 to 130/80 mm Hg, for young patients eGFR > 60 without significant CV morbidities. Once again, this was RASi-based therapy.

Sodium Restriction

Less than 2 grams per day of sodium (<5 grams of NaCl).

Tolvaptan

• Used in high-risk patients (Mayo 1C, 1D, 1E), or young+CKD, or young+large kidneys, or PROPKD > 6.
• Slows increased in TKV, slows decline in eGFR, and reduces kidney pain
• May extend the time until CKD stage 5
• Contraindicated with significant liver disease, hypernatremia, volume depletion, diuretic use, urinary obstruction.

Autosomal Recessive PKD (ARPKD)

Clinical Manifestations

Classic ARPKD

• Generally diagnosed in utero or within the neonatal period
• Greatly enlarged echogenic kidneys are seen in diseased fetuses
• Reduced fetal urine production --> oilgohydramnios + pulmonary hypoplasia (Potter sequence)
• 30% die after birth due to respiratory insufficiency
• 60% die within the first month
• Most patients are born with renal insufficiency and ESRD
• Infants often have a transient improvement in their GFR; death from renal insufficiency at this stage is rare

Older group ARPKD

• Systemic hypertension
• Progressive renal failure more due to fibrosis than to cystic destruction
• Liver manifestations
  • Biliary dysgenesis due to primary ductal plate malformation with periportal fibrosis
    • Congenital hepatic fibrosis (CHF)
    • Dilatation of intrahepatic bile ducts (Caroli disease)
  • Portal HTN

Diagnosis

• Diagnosis can be made in utero after 24 weeks of gestation in severe cases
• Macrocysts are not common at birth
• Parents will not have cysts (autosomal recessive)
• Imaging: US / CT / MRI are all used

Management

• Once again, there is no specific therapy
• Neonatal intensive care
• BP control
• Dialysis as needed
• Kidney transplantation
• Liver transplantation for liver fibrosis complications

References