What is the treatment for Autosomal Dominant (AD) Polycystic Kidney Disease (PKD)?

From the Guidelines

The treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) should focus on managing symptoms and slowing disease progression with the use of tolvaptan, a vasopressin-2 receptor antagonist, as the cornerstone of treatment in people with ADPKD at risk of rapid kidney disease progression, as recommended by the KDIGO 2025 clinical practice guideline 1.

Key Components of Treatment

• Tolvaptan should be initiated with a daily dose of 45 mg upon waking, and of 15 mg 8 hours later, and titrated gradually by the treating physician to permit adequate treatment 1.
• Patients should maintain adequate hydration (2-3 liters daily) and follow a low-sodium diet (less than 2,300 mg daily) to reduce polyuria and slow disease progression 1.
• Regular monitoring of kidney function, blood pressure, and cyst growth is essential to adjust treatment and prevent complications 1.
• Pain management may include acetaminophen or, if necessary, opioids for severe pain, and patients should avoid nephrotoxic medications like NSAIDs 1.

Lifestyle Modifications

• A healthy lifestyle including physical activity and maintenance of normal weight should be promoted in all patients with ADPKD to slow disease progression 1.
• Patients should limit caffeine and alcohol consumption to reduce the risk of complications 1.

Monitoring and Follow-up

• Regular liver function monitoring is necessary due to the potential hepatotoxicity of tolvaptan 1.
• Patients should have a "sick-day plan" and be advised to skip doses of tolvaptan in situations in which they are at risk of volume depletion 1.
• Genetic counseling is recommended for family planning, and patients should be referred for combined kidney-liver transplantation if an indication is present for liver transplantation and the kidney function is severely impaired 1.

From the Research

Treatment Overview

The treatment for Autosomal Dominant (AD) Polycystic Kidney Disease (PKD) involves a combination of lifestyle modifications and pharmacological interventions.

• Optimization of lifestyle, including blood pressure control, exercise, low-salt diet, and high volume water intake, is recommended 2.
• Pharmacological treatment may include:
  • ACE inhibitors or angiotensin receptor blockers to slow the progression of ADPKD 3, 4.
  • Statins for patients with lipid disorders and cardiovascular disease 3.
  • Tolvaptan for patients with stage I-III CKD and rapidly progressive ADPKD 3, 5, 6.

Pharmacological Treatment

• Tolvaptan is the only FDA-approved drug for the treatment of ADPKD, and it has been shown to slow cyst progression 5, 6.
• However, tolvaptan is moderately effective and may have significant side effects, leading to high patient dropout rates 5, 6.
• Other potential therapeutic strategies are being investigated, including mammalian target of rapamycin and dual kinase inhibitors, compounds that target inflammation and histone deacetylases, RNA-targeted therapeutic strategies, and glucosylceramide synthase inhibitors 6.

Barriers to Treatment Adherence

• Patient beliefs and confusion due to unclear recommendations may be barriers to adherence to prescribed therapies 2.
• Variability between what patients understand about their disease and treatments and what they believe their doctors have told them may also affect adherence 2.
• Patients may be motivated and willing to incorporate lifestyle modifications into their daily routines, but may require specific recommendations and guidance from their healthcare providers 2.