Tolvaptan in ADPKD Patients With Very Low Kidney Function

Area of Science:

• Nephrology
• Pharmacology

Background:

• Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by progressive kidney function decline.
• Tolvaptan has demonstrated efficacy in slowing estimated glomerular filtration rate (eGFR) decline in ADPKD patients in prior trials.
• The effects of tolvaptan in patients with more advanced kidney disease (eGFR 15-24 ml/min/1.73 m² ) remained uninvestigated.

Purpose of the Study:

• To retrospectively investigate the effect of tolvaptan on eGFR decline in ADPKD patients with baseline eGFR between 15 and 29 ml/min/1.73 m².
• To compare the eGFR decline in patients who initiated tolvaptan in an open-label extension (OLE) trial versus those who received placebo in the REPRISE trial.
• To assess the maintenance of tolvaptan's therapeutic effect in patients who continued treatment.

Main Methods:

• A post-hoc analysis of data from the REPRISE trial and its open-label extension (OLE).
• Two patient subsets were analyzed: 1) those with OLE baseline eGFR 15-29 ml/min/1.73 m² who received placebo in REPRISE and then tolvaptan in OLE; 2) those who received tolvaptan in REPRISE and were matched to placebo-treated patients.
• Annualized eGFR slopes were compared between treatment groups (placebo vs. tolvaptan) within each subset.

Main Results:

• Tolvaptan treatment resulted in significantly slower annualized eGFR decline compared to placebo across all analyzed subgroups.
• For subjects with OLE baseline eGFR 15-29 ml/min/1.73 m², the mean annualized eGFR slope was -3.4 ml/min/1.73 m² with tolvaptan versus -5.2 with placebo (difference 1.7, P < 0.001).
• Similar significant benefits were observed for subgroups with baseline eGFR 15-24 and 25-29 ml/min/1.73 m². Treatment effect was maintained in patients continuing tolvaptan.

Conclusions:

• Initiating tolvaptan therapy significantly delays eGFR decline in ADPKD patients with baseline eGFRs of 15-24 and 25-29 ml/min/1.73 m².
• Maintaining tolvaptan therapy preserves its beneficial effect on slowing kidney function decline.
• These findings support the use of tolvaptan in a broader range of ADPKD patients, including those with moderately advanced kidney disease.