Real clinical experience after one year of treatment with tolvaptan in patients with autosomal dominant polycystic kidney disease

Javier Naranjo; Francisco Borrego; José Luis Rocha; Mercedes Salgueira; Maria Adoración Martín-Gomez; Cristhian Orellana; Ana Morales; Fernando Vallejo; Pilar Hidalgo; Francisca Rodríguez; Remedios Garófano; Isabel González; Rafael Esteban; Mario Espinosa

doi:10.3389/fmed.2022.987092

Real clinical experience after one year of treatment with tolvaptan in patients with autosomal dominant polycystic kidney disease

Front Med (Lausanne). 2022 Sep 29:9:987092. doi: 10.3389/fmed.2022.987092. eCollection 2022.

Authors

Javier Naranjo¹, Francisco Borrego², José Luis Rocha³, Mercedes Salgueira⁴, Maria Adoración Martín-Gomez^{5

6}, Cristhian Orellana¹, Ana Morales⁷, Fernando Vallejo⁸, Pilar Hidalgo⁹, Francisca Rodríguez¹⁰, Remedios Garófano¹¹, Isabel González¹², Rafael Esteban^{5

13

14}, Mario Espinosa¹⁵

Affiliations

¹ Department of Nephrology, Hospital Universitario Puerta del Mar, Cádiz, Spain.
² Department of Nephrology, Complejo Hospitalario de Jaén, Jaén, Spain.
³ Department of Nephrology, Hospital Universitario Virgen del Rocío, Seville, Spain.
⁴ Department of Nephrology, Hospital Universitario Virgen del Macarena, Seville, Spain.
⁵ Grupo de Estudio de la Enfermedad Poliquística Autosómica Dominante (GEEPAD), Granada, Spain.
⁶ Department of Nephrology, Hospital de Poniente, El Ejido, Spain.
⁷ Department of Nephrology, Hospital Universitario San Cecilio, Granada, Spain.
⁸ Department of Nephrology, Hospital Universitario Puerto Real, Puerto Real, Spain.
⁹ Department of Nephrology, Hospital Regional Universitario de Málaga, Málaga, Spain.
¹⁰ Department of Nephrology, Hospital Costa del Sol, Marbella, Spain.
¹¹ Department of Nephrology, Hospital Universitario Torrecardenas, Almería, Spain.
¹² Department of Nephrology, Hospital Universitario Juan Ramón Jiménez, Huelva, Spain.
¹³ Department of Nephrology, Hospital Universitario Virgen de las Nieves, Granada, Spain.
¹⁴ Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain.
¹⁵ Department of Nephrology, Hospital Universitario Reina Sofia, Córdoba, Spain.

Abstract

Background: Tolvaptan (TV) is the first vasopressin-receptor antagonist approved for the treatment of autosomal dominant polycystic kidney disease (ADPKD). No publications report TV experience in real clinical practice during the first year of treatment.

Methods: A prospective study of an initial cohort of 220 rapidly progressing patients treated with TV for 12 months. The tolerability of TV, the evolution of the estimated glomerular filtration rate (eGFR), analytical parameters, and blood pressure were analyzed.

Results: A total of 163 patients (78.2%) received TV for 1 year. The main causes of treatment withdrawal were the aquaretic effects (11%), eGFR deterioration (5%), and hepatic toxicity (2.3%). eGFR decreased significantly after 1 month of treatment without further changes. The decrease in eGFR in the first month was higher in patients with an initially higher eGFR. The eGFR drop during the first year of treatment with TV was lower than that reported by patients in the 2 years prior to TV treatment (-1.7 ± 7.6 vs. -4.4 ± 4.8 mL/min, p = 0.003). Serum sodium and uric acid concentrations increased, and morning urinary osmolality decreased in the first month, with no further changes. Blood pressure decreased significantly without changes in antihypertensive medication.

Conclusion: TV treatment is well tolerated by most patients. Liver toxicity is very rare and self-limited. TV reduces eGFR in the first month without showing further changes during the first year of treatment. Patients with a higher starting eGFR will suffer a greater initial drop, with a longer recovery. We suggest using the eGFR observed after a month of treatment as the reference for future comparisons and calculating the rate of eGFR decline in patients undergoing TV treatment.

Keywords: glomerular filtration rate (eGFR); hepatic toxicity; polycystic kidney disease (PKD); tolvaptan; urinary osmolality.