Initiating or maintaining tolvaptan therapy significantly delayed estimated glomerular filtration rate (eGFR) decline in patients with baseline eGFR of 15-24 and 25-29 ml/min per 1.73 m2, according to a study published in Kidney International Reports.
Results from the TEMPO 3:4 and REPRISE trials indicated that treatment with tolvaptan was successful in slowing eGFR decline in patients with autosomal dominant polycystic kidney disease (ADPKD); however effects of the agent in patients with eGFR levels of 15-24 ml/min per 1.73 m2 were not investigated. For a post hoc analysis, Vincente Torres, MD, PhD, and colleagues compared eGFR decline as reported in REPRISE with that from an open-label, phase IIIb extension trial (OLE) in patients who received placebo during REPRISE and tolvaptan in OLE with eGFRs of 15-24 and 25-29 ml/min per 1.73 m2, respectively.
“One data subset comprised subjects with OLE baseline eGFR 15 to 29 ml/min per 1.73 m2 who had received placebo in REPRISE and began tolvaptan in OLE,” wrote Dr. Torres and colleagues. “The second comprised subjects who had received tolvaptan in REPRISE and were matched to REPRISE placebo-treated subjects for REPRISE baseline characteristics. Annualized eGFR slopes in REPRISE versus OLE were compared within the REPRISE placebo (i.e., placebo vs. tolvaptan treatment) and tolvaptan (i.e., 2 periods of tolvaptan treatment) subsets.”
The mean annualized eGFR slopes (ml/min per 1.73 m2) during tolvaptan treatment in the OLE trial versus during placebo treatment during REPRISE were -3.4 and -5.2 (a significant treatment effect of 1.72), respectively, among all participants in the overall REPRISE placebo subset. Corresponding slopes for those with baseline eGFRs of 15-24 and 25-29 were -3.6 versus -5.4 and -3.3 versus -4.9, respectively. “These results suggest that initiating tolvaptan therapy can significantly delay eGFR decline compared with no treatment in subjects with eGFR 15 to 24, including those with eGFR 25 to 29,” wrote the study authors. Treatment effect was maintained, with no difference observed between mean annualized eGFR slopes, among participants on tolvaptan during REPRISE who continued tolvaptan in the OLE trial.