Long-Term Effects of High-Dose Tolvaptan for Autosomal Dominant Polycystic Kidney Disease Patients

Abstract

Tolvaptan, a vasopressin V2 receptor antagonist, was initially approved in Japan for treatment of autosomal dominant polycystic kidney disease (ADPKD). Recently, a retrospective study showed that the effect of tolvaptan on kidney function could be sustained for a long period. However, the long-term efficacy and safety of high-dose tolvaptan (120 mg/day) in individual cases remain unknown. We report here 2 Japanese ADPKD patients (males, 36 and 29 years old) treated with tolvaptan (120 mg/day) for 9 years, during which time determinations of estimated glomerular filtration rate (eGFR) and total kidney volume (TKV) were performed. In these 2 patients, eGFR prior to therapy was 57.3 and 76.3 mL/min/1.73 m 2 , respectively, and 30.2 and 43.5 mL/min/1.73 m 2 , respectively, after 9 years of tolvaptan treatment, for a relatively constant annual decline of -3.01 and -3.64 mL/min/1.73 m 2 , respectively. As compared to the predicted (calculated) eGFR without tolvaptan treatment, eGFR actually measured was higher Case Rep Nephrol Dial Nakatani et al.: Long-Term Effects of High-Dose Tolvaptan for Autosomal Dominant Polycystic Kidney Disease Patients 10by 15.3 and 12.6 mL/min/1.73 m 2 , respectively, after the 9-year therapy period. In addition, the rate of TKV increase was gradual, 2.4 and 4.7%, respectively, per year during the initial 3-year period, to 6.5 and 12.5%, respectively, per year in the following 6-year period. During the 9 years of treatment, neither patient showed tolvaptan-related adverse events. Our findings suggest that long-term administration of tolvaptan at a high dose is both safe and effective to preserve kidney function, though a gradual increase in TKV was seen in both of the present cases, particularly during the later phase.

Autosomal dominant polycystic kidney disease: A case report

“…Tolvaptan should be given at 45 mg postoperative initially on waking and 15 mg taken 8 h later (i.e. 60 mg.day) [14]. A study also showed that long-term administration of tolvaptan at a high dose is both safe and effective to reserve kidney function, though a gradual increase in total kidney volume was seen, particularly during the later phase [15].…”