Urinary Aquaporin 2 as a Potential Indicator Predicting Tolvaptan Response in Patients With ADPKD

Shiho Makabe; Shun Manabe; Hiroshi Kataoka; Taro Akihisa; Rie Yoshida; Yusuke Ushio; Masayo Sato; Ken Tsuchiya; Toshio Mochizuki; Kosaku Nitta

doi:10.1016/j.ekir.2021.06.033

Urinary Aquaporin 2 as a Potential Indicator Predicting Tolvaptan Response in Patients With ADPKD

Kidney Int Rep. 2021 Jul 14;6(9):2436-2444. doi: 10.1016/j.ekir.2021.06.033. eCollection 2021 Sep.

Authors

Affiliations

¹ Department of Nephrology, Tokyo Women's Medical University, Tokyo Japan.
² Department of Blood Purification, Tokyo Women's Medical University, Tokyo, Japan.

Abstract

Introduction: Tolvaptan is used to treat autosomal dominant polycystic kidney disease (ADPKD) because it inhibits binding of the antidiuretic hormone vasopressin to the vasopressin V2 receptor (V2R), which suppresses the insertion of preformed water channel aquaporin 2 (AQP2) molecules in the luminal membrane of the collecting duct cells.

Methods: This single-center, prospective observational cohort study investigated whether decreased AQP2 elimination in urine affects the renal prognosis of patients who received tolvaptan. We selected 92 patients with ADPKD who were administered tolvaptan in our hospital. We evaluated correlations between changes in urinary AQP2 (U-AQP2) and clinical parameters and the annual change in total kidney volume (TKV) and estimated glomerular filtration rate (eGFR) as renal prognostic factors using univariable and multivariable multiple regression analyses.

Results: The observation period was 2.4 ± 1.5 years. U-AQP2 per milligram of urinary creatinine (U-AQP2/Cr) decreased from 67.8 ± 50.6 to 20.7 ± 15.1 fmol/mg urinary creatinine after 1 month of tolvaptan treatment. This initial change in U-AQP2/Cr was correlated with high baseline U-AQP2/Cr, low baseline eGFR, and a large initial change in eGFR (baseline to 1 month). The initial change in U-AQP2/Cr (baseline to 1 month) was strongly correlated with the annual change in TKV and eGFR in multivariable analysis.

Conclusion: Initial decrease in U-AQP2/Cr in the first month of treatment reflects the pharmacologic effect of tolvaptan and could be an indicator of renal prognosis during tolvaptan treatment.

Keywords: aquaporin; autosomal dominant polycystic kidney disease; estimated glomerular filtration rate; prognostic factor; tolvaptan; total kidney volume.