We appreciate the interest in the "Consensus Document on Autosomal Dominant Polycystic Kidney Disease (ADPKD)".1,2 The problem of the concept of rapid progression is raised, which has not been resolved. KDIGO defines rapid progression as a loss of glomerular filtration rate (GFR) >5 ml/min/1.73 m2/year.3 Based on the results of the REPRISE trial, it does not appear to be an adequate definition to identify those ADPKD patients who may benefit from tolvaptan4; the group of patients under 55 years of age treated with placebo lost GFR at a rate of −4.60 ml/min/1.73 m2 in one year, and yet tolvaptan slowed the loss of GFR by 33%, a result offered by few or none of the chronic kidney disease (CKD) treatments. For instance, at 12 months neither dapagliflozin nor canagliflozin showed a difference in GFR compared to placebo.5,6 Therefore, an alternative definition of rapid progression must be sought and we have proposed one.

As indicated in the letter, REPRISE did not demonstrate benefit during the follow-up period (one year in the context of a disease with a natural history to renal replacement therapy of 58 years on average in Europe and Spain, with a peak between 50 and 65 years)7 in a subgroup characterised by an age greater than 55 years, but also by a slow progression with placebo (−2.34 ml/min/1.73 m2 in one year).4 The author of the letter emphasises the age of the patients. Still, from the pathophysiological point of view, it is not plausible that an effective treatment at 55 years of age ceases to be effective at age 56 years. It is plausible that it is difficult to assess the efficacy after one year of treatment in patients who progress slowly or that it is ineffective in patients who progress more slowly. However, the trajectory of GFR loss in ADPKD is not linear and it is accelerated with age.8 So a patient can become a rapid progressor after the age of 55. Therefore if the safety of tolvaptan has been demonstrated in ADPKD at least up to age of 60, we find no reason to deny the treatment to patients of 55 to 60 years of age, a treatment that has been accepted as effective by the EMA.

We share the concern for the rational use of resources. Accordingly, there is a generic version of tolvaptan. Still, dialysis continues to cost around 45,000/year/patient, and is associated with a considerable loss of quality of life and cardiovascular mortality 10–100 times higher than that of the general population.9