From the Guidelines
Tolvaptan (Jynarque) helps with polycystic kidney disease (PKD) by delaying disease progression in adults with autosomal dominant polycystic kidney disease (ADPKD) who are likely to develop end-stage renal disease (ESRD) 1.
Key Mechanism
The medication works as a vasopressin antagonist, which has been shown to reduce ADPKD-related pain and slow the decline in kidney function 1.
Clinical Use
While tolvaptan has been licensed for use in adults, its use in children and adolescents is still being studied, with ongoing trials investigating its safety and efficacy in this population 1.
Important Considerations
It is essential to note that tolvaptan can cause hepatic injury and polyuria, which may affect sleep and daily activities, and thus impact quality of life 1.
Current Recommendations
Currently, vasopressin antagonists like tolvaptan are not recommended for routine use in children with ADPKD, but may be considered off-label in selected cases 1.
The FDA Drug Labels for tolvaptan (PO) do not address this question.
From the Research
Mechanism of Action
- Tolvaptan is an orally active, selective arginine vasopressin V2 receptor antagonist that exhibits dose-proportional pharmacokinetics with a half-life of ~12 hours 2.
- It targets underlying pathogenic mechanisms of autosomal dominant polycystic kidney disease (ADPKD) by delaying the increase in total kidney volume and slowing the decline in renal function 2, 3.
Efficacy
- Tolvaptan has been shown to slow kidney function decline in subjects with ADPKD at risk of rapid progression 3.
- It also reduces kidney pain and slows the growth of total kidney volume (TKV) 2, 4.
- A pooled data analysis of long-term treatment effects of tolvaptan in ADPKD demonstrated that tolvaptan slowed annualized eGFR decline by 1.01 ml/min per 1.73 m2 versus standard of care over 5.5 years 3.
Patient Selection and Outcomes
- Appropriate patient selection is critical to optimize long-term benefits while minimizing adverse effects and hepatotoxic risk factors 2.
- Younger patients with a relatively preserved e-GFR, lower hypertension burden, better familial renal prognosis, and more severe imaging data showed better outcomes with tolvaptan treatment 4.
- Tolvaptan seems to be effective in preventing progression of ADPKD when administered in a timely manner in patients with better familial renal history, shorter hypertension duration, and worse imaging profile 4.
Safety and Adverse Effects
- Tolvaptan has significant adverse effects, including aquaretic effects (polyuria, nocturia, polydipsia) and elevation of aminotransferase enzyme concentrations with the potential for acute liver failure 2.
- The aquaretic adverse effects of tolvaptan did not affect renal function and electrolyte balance in patients with ADPKD 4.