Pharmaceutical Treatment Trends and Criteria for ADPKD

Current Treatment Landscape

• The American College of Cardiology is not mentioned, however, the Kidney International journal recommends Tolvaptan as the only FDA-approved disease-modifying therapy that slows eGFR decline by approximately 1.3 ml/min/1.73 m² per year and reduces total kidney volume growth by 2.7% compared to placebo 1, 3
• The National Institute of Health does not have a direct recommendation, but the Nature Reviews Nephrology journal states that mTOR inhibitors should NOT be used in ADPKD patients, as prospective RCTs found no eGFR benefit and significant adverse effects including worsening proteinuria, hyperlipidemia, and cytopenias 4, 5, 6
• The European Renal Association recommends that Somatostatin analogues are not recommended for renal disease progression, though they may benefit severe polycystic liver disease without sustained renal benefit 4, 5, 1

Criteria for Initiating Tolvaptan

• The Kidney International journal identifies patients who will benefit most from treatment, including those with large total kidney volume (height-adjusted TKV >600 mL/m or Mayo Class 1C-1E) 1, 2
• The Kidney International journal also recommends treatment for patients with rapid kidney growth rate (>5% annual increase in TKV) 1, 3
• The Kidney International journal identifies declining eGFR with evidence of progressive loss as a criterion for treatment 1, 3
• The Kidney International journal states that PKD1 mutation is associated with more severe disease than PKD2 1
• The Nature Reviews Nephrology journal recommends considering family history of early-onset kidney failure (before age 58) as a criterion for treatment 7, 8

Mandatory Monitoring Requirements

• The Praxis Medical Insights recommends monthly liver function tests for the first 18 months, then every 3 months thereafter until discontinuation 2, 3
• The Praxis Medical Insights recommends permanently discontinuing treatment if ALT or AST ≥3× upper limit of normal or if >2× ULN with signs/symptoms of liver injury 2, 3

Critical Management Considerations

• The Kidney International journal recommends that patients must drink 2-3 liters of water daily to replace urinary losses from aquaresis 2, 3
• The Kidney International journal advises counseling patients to drink liquids without sugar or fat and adopt low-sodium intake to reduce polyuria 1, 2, 3

Pediatric Considerations

• The Nature Reviews Nephrology journal states that vasopressin antagonists are NOT routinely recommended for children and young people with ADPKD 4, 5, 6, 7, 8
• The Nature Reviews Nephrology journal recommends considering off-label use in children at high risk of early progression based on large total kidney volume, rapid kidney growth, or concerning family history 7, 8, 2, 3

Supportive Measures (Not Disease-Modifying)

• The Nature Reviews Nephrology journal recommends low dietary salt intake 4, 5, 6
• The Nature Reviews Nephrology journal suggests high water intake (2-3 liters daily) and avoidance of excessive protein intake may be beneficial 4, 5, 6
• The Nature Reviews Nephrology journal advises promoting physical activity and maintenance of normal weight 4, 5, 6
• The Nature Reviews Nephrology journal recommends avoiding chronic NSAID use due to potential renal adverse effects 4, 6, 8