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

From the Guidelines

Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) should focus on slowing disease progression with tolvaptan, a vasopressin V2 receptor antagonist, as the cornerstone medication, initiated at 45mg in the morning and 15mg in the afternoon, with potential titration to 90/30mg daily as tolerated, as recommended by the most recent guideline 1. The goal of treatment is to delay the progression of kidney disease and manage complications.

• Tolvaptan has been shown to slow kidney cyst growth by reducing cAMP levels in kidney tubules, with a net difference in eGFR decline of 1.3 ml/min per 1.73 m2 per year and in total kidney volume growth of 2.7% favoring tolvaptan use 1.
• Blood pressure control is essential, with ACE inhibitors or ARBs as first-line agents, such as lisinopril 10-40mg daily or losartan 25-100mg daily, to target BP below 130/80 mmHg, or more aggressively to <120 mm Hg if tolerated in those aged ≥50 years and/or with CKD G3–G5 1.
• Patients should maintain adequate hydration with 2-3 liters of water daily to reduce vasopressin levels and limit caffeine and sodium intake.
• Regular monitoring of kidney function, blood pressure, and screening for complications like intracranial aneurysms (particularly in those with family history) is important.
• For patients progressing to end-stage kidney disease, timely preparation for renal replacement therapy, including transplantation evaluation, is necessary.
• Genetic counseling should be offered to patients of reproductive age. It is also important to note that a healthy lifestyle, including physical activity and maintenance of normal weight, should be promoted in all patients with ADPKD, as recommended by international consensus statement 1.

From the FDA Drug Label

Tolvaptan should not be used to treat ADPKD outside of the FDA-approved risk evaluation and mitigation strategy (REMS) for ADPKD patients Tolvaptan tablets are contraindicated in the following conditions: • Patients with autosomal dominant polycystic kidney disease (ADPKD) outside of FDA-approved REMS

The FDA drug label does not provide information on the treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD). It only mentions that tolvaptan should not be used to treat ADPKD outside of the FDA-approved REMS.

From the Research

Treatment Options for ADPKD

The treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD) involves a combination of lifestyle modifications and pharmacological interventions. Some of the key treatment options include:

• Optimization of lifestyle
• Combined pharmacological treatment with:
  • ACE inhibitors or angiotensin receptor blockers 2
  • Statins (for patients with lipid disorders and cardiovascular disease) 2
  • Tolvaptan (for patients with stage I-III CKD and rapidly progressive ADPKD) 2, 3
• Inhibition of the RAA system to slow progression of ADPKD 2
• Management of renal complications, including cyst infection, nephrolithiasis, haematuria, and chronic pain 4

Pharmacological Interventions

Several pharmacological interventions are being tested for the treatment of ADPKD, including:

• Mammalian target of rapamycin inhibitors 3, 5
• Somatostatin analogues 5
• Vasopressin V2 receptor antagonists 5
• Dual kinase inhibitors 3
• Compounds that target inflammation and histone deacetylases 3
• RNA-targeted therapeutic strategies 3
• Glucosylceramide synthase inhibitors 3

Non-Pharmacological Interventions

Non-pharmacological interventions, such as dietary restriction, may also be beneficial in the treatment of ADPKD 3. Additionally, tissue targeting to renal cysts of small molecules via the folate receptor, and of monoclonal antibodies via the polymeric immunoglobulin receptor, may be a potential way to reduce extra-renal side effects 3.