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. 2021 Mar;25(3):251-260.
doi: 10.1007/s10157-020-01988-4. Epub 2020 Nov 3.

Effect of tolvaptan on renal involvement in patients with autosomal dominant polycystic kidney disease according to different gene mutations

Tomofumi Moriyama  1 , Yosuke Nakayama  1 , Mikiko Soejima  2 , Yunosuke Yokota  1 , Kanji Ota  1 , Sakuya Ito  1 , Goh Kodama  1 , Nao Nakamura  1 , Yuka Kurokawa  1 , Junko Yano  1 , Utako Ueda  1 , Yoshimi Takamiya  1 , Yusuke Kaida  1 , Takuma Hazama  1 , Ryo Shibata  1 , Yoshiro Koda  2 , Kei Fukami  3
Affiliations

Effect of tolvaptan on renal involvement in patients with autosomal dominant polycystic kidney disease according to different gene mutations

Tomofumi Moriyama et al. Clin Exp Nephrol. 2021 Mar.

Abstract

Background: Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder caused by mutations in the polycystic kidney disease (PKD) gene. Although tolvaptan has benefits for renal involvement, the different effects depending on the gene mutation type are unknown. Thus, we explore the different effects of tolvaptan on the annual changes in total kidney volume (%TKV) and estimated glomerular filtration rate (eGFR) according to the gene mutation type in ADPKD patients.

Methods: In total, 135 ADPKD patients were screened, and 22 patients taking tolvaptan for at least a year were retrospectively studied at the Kurume University Hospital. We examined the decline in renal function and %TKV by computed tomography and analyzed the gene mutation. Patients were classified into the following four groups according to gene mutation type: PKD1-truncated, PKD1-non-truncated, PKD2, and mutation not found. Patients were treated with tolvaptan, and the effects of tolvaptan were analyzed according to the gene mutation type.

Results: Patients (age: 52.3 ± 11.2 years) were administered tolvaptan at a dose of 45 or 60 mg. No variation was observed in the annual changes in eGFR (%eGFR) (before: - 10.5% ± 13.9%, after: - 14.4% ± 8.1%, P = 0.139), whereas %TKV was significantly improved after the tolvaptan treatment (before: 14.9% ± 8.0%, after: - 5.4% ± 7.6%, P < 0.001). Unlike %eGFR, tolvaptan treatment significantly improved %TKV, regardless of the type of gene mutation.

Conclusions: A year treatment with tolvaptan significantly improved %TKV in patients with ADPKD, regardless of the gene mutation type.

Keywords: Autosomal dominant polycystic kidney disease; PKD1; PKD2; Renal function; Tolvaptan; Total kidney volume.

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Conflict of interest statement

K. Fukami and T. Moriyama have received personal fees and research grant from Otsuka Pharmaceutical Co., Ltd. outside of the submitted work.

Figures

Fig. 1
Fig. 1
Flowchart of the study. ADPKD autosomal dominant polycystic kidney disease, TKV total kidney volume
Fig. 2
Fig. 2
Effects of tolvaptan on eGFR and change in eGFR and TKV. a eGFR levels at 1 year before and at 1 year after the tolvaptan treatment (n = 22). b Change in eGFR at 1 year before to at 1 year after the tolvaptan treatment (n = 22). c Change in TKV at 1 year before to at 1 year after the tolvaptan treatment (n = 22). eGFR estimated glomerular filtration rate, TKV total kidney volume
Fig. 3
Fig. 3
Effects of tolvaptan on changes in eGFR and TKV according to the type of gene mutation. Change in eGFR from at 1 year before to at 1 year after the tolvaptan treatment in patients with PKD1-T (a), PKD1-NT (b), PKD2 (c), or mutation not found. Change in TKV from at 1 year before to at 1 year after the tolvaptan treatment in patients with PKD1-T (e), PKD1-NT (f), PKD2 (g), or mutation not found. eGFR estimated glomerular filtration rate, TKV total kidney volume, PKD1-T polycystic kidney disease1-truncating gene mutation, PKD-NT polycystic kidney disease-non-truncating gene mutation
Fig. 4
Fig. 4
Dose of tolvaptan at initiation and at 1 year after the tolvaptan treatment
See this image and copyright information in PMC

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