Long-Term Effects of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease: Predictors of Treatment Response and Safety over 6 Years of Continuous Therapy

Long-Term Effects of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease: Predictors of Treatment Response and Safety over 6 Years of Continuous Therapy Mai Yamazaki Department of Urology, Graduate School of Medicine, Juntendo University, Tokyo 113-8431, Japan Haruna Kawano Department of Urology, Graduate School of Medicine, Juntendo University, Tokyo 113-8431, Japan Department of Advanced Informatics for Genetic Diseases, Graduate School of Medicine, Juntendo University, Tokyo 113-8431, Japan Miho Miyoshi Department of Urology, Graduate School of Medicine, Juntendo University, Tokyo 113-8431, Japan Tomoki Kimura Department of Urology, Graduate School of Medicine, Juntendo University, Tokyo 113-8431, Japan http://orcid.org/0009-0004-7434-8015 Keiji Takahashi Department of Urology, Graduate School of Medicine, Juntendo University, Tokyo 113-8431, Japan Satoru Muto Department of Advanced Informatics for Genetic Diseases, Graduate School of Medicine, Juntendo University, Tokyo 113-8431, Japan Department of Urology, Juntendo University Nerima Hospital, Tokyo 177-8521, Japan Shigeo Horie Department of Urology, Graduate School of Medicine, Juntendo University, Tokyo 113-8431, Japan Department of Advanced Informatics for Genetic Diseases, Graduate School of Medicine, Juntendo University, Tokyo 113-8431, Japan

Tolvaptan, an oral vasopressin V2 receptor antagonist, reduces renal volume expansion and loss of renal function in patients with autosomal dominant polycystic kidney disease (ADPKD). Data for predictive factors indicating patients more likely to benefit from long-term tolvaptan are lacking. Data were retrospectively collected from 55 patients on tolvaptan for 6 years. Changes in renal function, progression of renal dysfunction (estimated glomerular filtration rate [eGFR], 1-year change in eGFR [ΔeGFR/year]), and renal volume (total kidney volume [TKV], percentage 1-year change in TKV [ΔTKV%/year]) were evaluated at 3-years pre-tolvaptan, at baseline, and at 6 years. In 76.4% of patients, ΔeGFR/year improved at 6 years. The average 6-year ΔeGFR/year (range) minus baseline ΔeGFR/year: 3.024 (−8.77–20.58 mL/min/1.73 m2). The increase in TKV was reduced for the first 3 years. A higher BMI was associated with less of an improvement in ΔeGFR (p = 0.027), and family history was associated with more of an improvement in ΔeGFR (p = 0.044). Hypernatremia was generally mild; 3 patients had moderate-to-severe hyponatremia due to prolonged, excessive water intake in response to water diuresis—a side effect of tolvaptan. Family history of ADPKD and baseline BMI were contributing factors for ΔeGFR/year improvement on tolvaptan. Hyponatremia should be monitored with long-term tolvaptan administration.
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