ADPKD (Polycystic Kidney Disease)

Autosomal Dominant Polycystic Kidney Disease (ADPKD) – Treatment Options

Introduction
Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited renal disorder characterized by progressive formation and enlargement of fluid-filled cysts in both kidneys. Mutations in PKD1 or PKD2 genes lead to altered polycystin proteins, disrupting tubular cell signaling and promoting cyst growth. Clinical features include hypertension, hematuria, flank pain, urinary tract infections, nephrolithiasis, and progressive decline in kidney function, often leading to end-stage renal disease (ESRD). Extrarenal manifestations include hepatic cysts, intracranial aneurysms, and cardiac valve abnormalities. Treatment focuses on slowing disease progression, managing complications, and preserving renal function.

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1. General and Supportive Management

• Blood pressure control:

  • ACE inhibitors (enalapril) or ARBs (losartan) are preferred.

  • Strict control (<130/80 mmHg) slows progression.

• Pain management:

  • NSAIDs avoided due to nephrotoxicity; acetaminophen preferred.

  • Opiates or nerve blocks for refractory pain.

• Hydration:

  • High water intake suppresses vasopressin (AVP), potentially slowing cyst growth.

• Dietary modifications:

  • Low sodium intake (<2 g/day).

  • Avoid excessive caffeine (may promote cyst growth).

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2. Disease-Modifying Therapy

• Tolvaptan (vasopressin V2-receptor antagonist):

  • Only approved disease-modifying drug.

  • Slows cyst growth and decline in GFR in patients at risk of rapid progression.

  • Requires liver function monitoring (risk of hepatotoxicity).

• Somatostatin analogs (e.g., octreotide, lanreotide):

  • Studied for cyst reduction (mainly liver cysts), but not standard therapy.

• mTOR inhibitors (sirolimus, everolimus):

  • Investigational; limited benefit and significant side effects.

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3. Management of Complications

• Hypertension: ACE inhibitors/ARBs as cornerstone therapy.

• Urinary tract infections (UTIs):

  • Prompt antibiotics with cyst-penetrating agents (fluoroquinolones, TMP-SMX).

• Cyst infections:

  • Prolonged antibiotic therapy; drainage if refractory.

• Hematuria and cyst hemorrhage:

  • Conservative management (hydration, rest); rarely embolization.

• Kidney stones:

  • Hydration, stone prevention strategies, and urological interventions as needed.

• Liver cysts:

  • Somatostatin analogs, fenestration, or partial hepatectomy in severe cases.

• Intracranial aneurysms:

  • Screening (MRA/CTA) in high-risk patients; neurosurgical intervention if aneurysm detected.

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4. Advanced Disease and Renal Replacement Therapy

• Dialysis: Hemodialysis or peritoneal dialysis once ESRD develops.

• Kidney transplantation:

  • Definitive treatment for ESRD.

  • Excellent outcomes; native nephrectomy may be required for massively enlarged kidneys.

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5. Monitoring and Long-Term Care

• Renal function: Regular serum creatinine, eGFR, and urinalysis.

• Imaging: MRI or ultrasound to monitor kidney and cyst growth.

• Liver function tests: Especially in patients on tolvaptan.

• Family screening: First-degree relatives should be offered genetic counseling and imaging.

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6. Multidisciplinary Care

• Nephrologists: For disease monitoring, hypertension control, and renal replacement planning.

• Hepatologists: For management of liver cyst disease.

• Neurologists/neurosurgeons: For intracranial aneurysm screening and treatment.

• Urologists/interventional radiologists: For cyst drainage, embolization, and stone management.

• Genetic counselors: For family planning and early detection.