Effects of Octreotide-Long-Acting Release Added-on Tolvaptan in Patients with Autosomal Dominant Polycystic Kidney Disease: Pilot, Randomized, Placebo-Controlled, Cross-Over Trial

Background Tolvaptan and octreotide-long-acting release (LAR) have renoprotective effects in autosomal dominant polycystic kidney disease (ADPKD) that are partially mediated by amelioration of compensatory glomerular hyperfiltration. We comparedthe effects of tolvaptan and octreotide-LAR combination therapy versus those of tolvaptan monotherapy in patients with ADPKD. Methods This pilot, randomized, placebo-controlled, cross-over trial primarily compared the effects of 1- and 4-week treatments with octreotide-LAR (two 20-mg i.m. injections) or placebo (two i.m. 0.9% saline solution injections) added-ontolvaptan(upto 90 and 30mg/d) onGFR(iohexol plasma clearance) in 19 consentingpatients with ADPKD referred to a clinical research center in Italy. Analyses were intention-to-treat. The local ethical committee approved the study. Results At 4 weeks, GFR significantly decreased by a median (interquartile range) of 3 (-1 to 5) ml/min per 1.73 m(2) with tolvaptan and placebo (P=0.01) and by 7 (3-14) ml/min per 1.73 m(2) with tolvaptan and octreotide-LAR (P=0.03). GFR changes during the two treatment periods differed by 2 ( 25 to 14) ml/min per 1.73 m(2) (P=0.28). At 1 week, GFR significantly decreased by 3 (0-7) ml/min per 1.73 m(2) with tolvaptan and placebo ( P=0.006) and by 10 (-6 to 16) ml/min per 1.73 m(2) with tolvaptan and octreotide-LAR add-on therapy (P<0.001). GFR changes during the two treatment periods significantly differed by 3 ( 0-12) ml/ min per 1.73 m(2) (P50.012). Total kidney volume nonsignificantly changed by 4 ( 248 to 23) ml with tolvaptan and placebo ( P=0.74), whereas it decreased significantly by 41 (25-77) ml with tolvaptan and octreotide-LAR (P50.001). Changes during the two treatment periods differed by 36 (0- 65) ml (P=0.01). Octreotide-LAR also attenuated (P=0.02) the aquaretic effect of tolvaptan. Treatments were well tolerated. Conclusions In patients with ADPKD, octreotide-LAR added-on tolvaptan reduced GFR more effectively than octreotide- LAR and placebo. Octreotide-LAR also reduced total and cystic kidney volumes and attenuated the acquaretic effect of tolvaptan.