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

Abstract

BackgroundTolvaptan (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.MethodsA 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.ResultsA 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.ConclusionTV 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.

Interaction Between Determinants Governing Urine Volume in Patients With ADPKD on Tolvaptan and its Impact on Quality of Life

“…Previous data showed that tolvaptan therapy did not have a strong impact on QoL in general. 12 , 31 In the present study, therapy was well-tolerated, as measured by the SF-12 questionnaire, with mental and physical scores comparable with the normative German sample. Patients with high-frequency miction did not report to feel urine volume as a burden, similar to results of other studies.…”

Prospective Study on Individualized Dose Adjustment of Tolvaptan Based on Urinary Osmolality in Patients With ADPKD

“…High doses of tolvaptan are associated with increased side effects, leading to a higher dropout rate, 8 especially in patients with early-stage CKD. 21 In previous studies, the observed dropout rates varied as follows: 23% in TEMPO 3:4, 20 22% in a 1-year retrospective cohort from Andalusia, 22 and 56% in a recent 3-year retrospective cohort study from the United Kingdom. 23 The use of the maximum tolvaptan dose could contribute to these undesirable effects.…”

Recent updates in therapeutic approach using tolvaptan for autosomal dominant polycystic kidney disease

“…In the subgroup analysis, the effect of preserving kidney function was prominent in patients with more severe clinical phenotypes, similar to changes in TKV. Although there have been no reports considering ESKD as an outcome, the positive effect of preserving kidney function has been maintained in most studies [22,23]. Extrapolations from the results of the TEMPO 3:4 suggested that [24].…”