Polycystic Kidney Disease (PKD)

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Polycystic Kidney Disease (PKD)

Definition

Polycystic kidney disease (PKD) is a hereditary disorder characterized by the development of numerous fluid-filled cysts in both kidneys, leading to progressive enlargement, loss of renal function, and eventually end-stage renal disease (ESRD).
Two main forms exist:

  • Autosomal Dominant PKD (ADPKD) – most common, adult onset

  • Autosomal Recessive PKD (ARPKD) – rare, severe, often presents in infancy or childhood




Epidemiology

  • ADPKD

    • Incidence: ~1 in 1,000 (most common inherited cause of CKD)

    • Accounts for 5–10% of ESRD cases

  • ARPKD

    • Incidence: ~1 in 20,000

    • Severe infantile/childhood onset → mortality up to 40%

  • Affects both sexes equally.

  • ~140,000 patients diagnosed in the US.

Etiology & Genetics

  • ADPKD

    • Autosomal dominant inheritance (complete penetrance, variable expressivity)

    • Mutations:

      • PKD1 (chromosome 16) → polycystin-1 (~85% cases, more severe)

      • PKD2 (chromosome 4) → polycystin-2 (~15% cases, milder, later onset)

    • Positive family history is common.

  • ARPKD

    • Autosomal recessive inheritance

    • Mutation in PKHD1 (chromosome 6) → defective fibrocystin (polyductin)

    • Involves both kidneys and hepatobiliary system.

Pathophysiology

  • ADPKD

    • Two-hit hypothesis: inherited mutation + acquired mutation in renal tubule cells → cyst formation.

    • Defective polycystin-1 and -2 disrupt ciliary signaling, Ca²⁺ regulation, and tubular architecture.

    • Leads to progressive cyst expansion, renal ischemia, RAAS activation, hypertension, and kidney destruction.

  • ARPKD

    • Mutated fibrocystin → cystic dilatation of collecting ducts and bile ducts.

    • Associated with congenital hepatic fibrosis.

Clinical Features

ADPKD (usually adulthood, >30y)

  • Renal: flank/abdominal pain, hematuria, polyuria, recurrent UTIs, nephrolithiasis, CKD signs (uremia, fluid overload)

  • Extrarenal:

    • Hepatic cysts (most common extrarenal feature)

    • Pancreatic and splenic cysts

    • Colonic diverticulosis, abdominal hernias

  • Cardiovascular: hypertension, LV hypertrophy, mitral valve prolapse, pericardial effusion, aneurysms (coronary, aortic)

  • Neurological: intracranial berry aneurysms (~8%), risk of SAH

  • Other: bronchiectasis, ovarian/seminal vesicle cysts

ARPKD (infancy/childhood)

  • Severe cases: oligohydramnios → Potter sequence, pulmonary hypoplasia, craniofacial anomalies, talipes equinovarus

  • Enlarged kidneys, hepatomegaly, protruding abdomen

  • Early-onset hypertension, often resistant

  • CKD signs: hematuria, proteinuria, oliguria

  • Extrarenal: congenital hepatic fibrosis → portal hypertension, cholangitis, progressive liver failure

Diagnosis

  • Imaging

    • Ultrasound (first-line, especially in at-risk relatives)

      autosomal dominant polycystic kidney disease

      Liver involvement in polycystic kidney disease
       

      • ARPKD: bilateral enlarged echogenic kidneys, poor corticomedullary differentiation, hepatic fibrosis

    • ADPKD: multiple bilateral cysts, enlarged kidneys, hepatic/pancreatic cysts

    • MRI/CT: used if US is equivocal, or to measure total kidney volume (prognostic marker).


  • Genetic Testing

    • ADPKD: PKD1/PKD2 sequencing

    • ARPKD: PKHD1 analysis (gold standard)

  • Laboratory

    • ↑ creatinine/BUN (CKD progression), proteinuria, hematuria

    • CRP ↑ in cyst infection

  • Additional evaluations in ADPKD

    • MR angiography (intracranial aneurysms if high risk)

    • Echocardiography (valve disease, LVH, effusion)

    • Annual BP monitoring from age 5 if family history present

Differential Diagnosis

  • Acquired cystic kidney disease (CKD/dialysis patients)

  • Multicystic dysplastic kidney

  • Medullary sponge kidney

  • Autosomal dominant tubulointerstitial kidney disease (ADTKD)

  • Nephronophthisis

  • Von Hippel-Lindau disease

Treatment & Management

  • General measures

    • Nephrology follow-up

    • Blood pressure control (ACE inhibitors or ARBs preferred)

    • Low-sodium, moderate-protein diet, weight management

    • High fluid intake (may slow cyst growth and prevent stones)

    • Early treatment of UTIs

    • Avoid nephrotoxins (NSAIDs, aminoglycosides, vasopressin agonists)

  • Disease-modifying therapy

    • Tolvaptan (vasopressin V2-receptor antagonist)

      • Slows cyst growth and CKD progression in ADPKD with eGFR ≥25 mL/min/1.73m² and risk of rapid decline

      • Monitor liver function (risk of hepatotoxicity)

      • Not effective in ARPKD

  • Management of complications

    • Hematuria/cyst hemorrhage → supportive, rest, fluids

    • Cyst infection → prolonged IV antibiotics (fluoroquinolones), drainage if refractory

    • Nephrolithiasis → standard management + prevention (hydration, citrate)

    • Hepatic cysts → aspiration/sclerotherapy or surgery if symptomatic

    • SAH/aneurysm → neurosurgical management

    • Portal hypertension (ARPKD) → supportive or surgical

  • Renal Replacement Therapy

    • Dialysis when ESRD develops

    • Kidney transplantation = only curative option

    • Combined liver-kidney transplant may be required in ARPKD with severe hepatic fibrosis

Prognosis

  • ADPKD: most patients progress to ESRD by age 50–70, earlier with PKD1 mutations.

  • ARPKD: severe neonatal cases carry poor prognosis due to pulmonary hypoplasia; survivors develop CKD and liver disease.

✅ Summary Pearl:

  • ADPKD = common, adult-onset, kidney + liver cysts, aneurysm risk.

  • ARPKD = rare, childhood-onset, kidney + liver fibrosis, respiratory complications.

  • Only curative treatment: kidney transplantatio

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