Recommendations Issued for Tolvaptan Use in ADPKD
ERA-EDTA offers guidance on selecting patients for treatment, when to start the drug, dosing strategies, and other aspects of care.
The European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) has published a consensus document containing recommendations for the use of tolvaptan in patients with autosomal dominant polycystic kidney disease (ADPKD).
In May 2015, the European Medicines Agency approved the use of tolvaptan, a vasopressin V2 receptor antagonist, for slowing progression of cyst development and renal insufficiency in adult ADPKD patients with CKD stages 1–3 at initiation of treatment and evidence of rapidly progressing disease. This makes tolvaptan the first pharmaceutical agent approved for slowing disease progression in ADPDK. Tolvaptan was originally approved for the treatment of hyponatremia, and in the United States, it is only approved for that use. The FDA in 2014 asked for additional efficacy and safety data.
The recommendations are based on the consensus of ADPKD experts and methodologists in the ERA-EDTA Working Groups on Inherited Kidney Disorders and European Renal Best Practice. In the consensus document, which was published online in Nephrology Dialysis Transplantation (NDT), the ERA-EDTA suggests that tolvaptan can be prescribed to adult ADPKD patients younger than 50 years with CKD stages 1–3a (an estimated glomerular filtration rate [eGFR] greater than 45 mL/min/1.73 m2) who have demonstrated or who are likely to have rapidly progressing disease.
ERA-EDTA recommends not starting tolvaptan in patients aged 30–40 years with CKD stage 1 (eGFR greater than 90 mL/min/1.73 m2) or patients aged 40–50 years with CKD stages 1 or 2 (eGFR greater than 60 mL/min/1.73 m2).
The organization recommends that rapid disease progression be defined as a confirmed annual eGFR decline of at least 5 mL/min/1.73 m2 in 1 year, and/or at least 2.5 mL/min/1.73 m2 per year over a period of 5 years. It can also be defined as a greater than 5% increase in total kidney volume per year by repeated measurements (preferably 3 or more, each at least 6 months apart and by magnetic resonance imaging).
With regard to dosing, ERA-EDTA suggests that tolvaptan be started with a dose of 45 mg in the morning and 15 mg in the evening, uptitrating the dose to 50/30 and 90/30 when tolerated, and discontinuing tolvaptan when patients approach end-stage renal disease.
In the NDT paper, the organization has proposed a hierarchical decision algorithm to assess whether treatment is warranted.
“Even though consensus documents are inherently weak for producing recommendations for clinical practice, these treatment recommendations may be useful to doctors and patients,” NDT Editor-in-Chief Carmine Zoccali, MD, said in a press release. He added that tolvaptan has a number of limitations and side effects and it probably is only suitable for a minority of patients.