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

Abstract

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent genetic cause of kidney failure. Tolvaptan, a vasopressin 2 receptor antagonist, is the first drug with proven disease-modifying activity. Long-term treatment adherence is crucial, but a considerable fraction of patients discontinue treatment, because of aquaretic side effects.

Methods: Twenty-four-hour urine was collected in 75 patients with ADPKD during up-titration of tolvaptan and, in combination with clinical characteristics, examined to identify factors influencing urine volume. Patient-reported outcomes were analyzed using the Short Form-12 (SF-12) and patient-reported outcomes questionnaires reporting micturition frequency and burden of urine volume.

Results: Initiation of therapy led to a large increase in urine volume followed by only minor further increase during up-dosing. Younger patients and patients with better kidney function experienced a larger relative rise. Twenty-four-hour urine osmolality dropped by about 50% after therapy initiation independently of dose, with a considerable proportion of patients achieving adequate suppression. Sodium and potassium intake turned out to be the only significant modifiable factors for urine volume after multivariate linear regression models, whereas age and weight could be identified as non-modifiable factors. No change in quality of life (QoL) was detected in relation to treatment or urine volume using SF-12 questionnaires, a finding that was further supported by the results of the patient-reported outcomes assessment.

Conclusion: This study provides an in-detail analysis of factors associated with the degree of polyuria on tolvaptan and puts them into the context of QoL. These findings will contribute to optimized patient counseling regarding this treatment option in ADPKD.

Keywords: ADPKD; dose; osmolality; quality of life; tolvaptan; urine volume.

Graphical abstract

Figure 1

Study flow chart. Study flow chart depicting patient flow, exclusion criteria, and subgroup analyses. ADPKD, autosomal dominant polycystic kidney disease

Figure 2

Urine parameters among different Tolvaptan dosing steps. 24-hour urine volume (a), urine osmolality (b) and total daily intake of osmoles (c). Details concerning the statistical tests can be found in Supplementary Table S1.

Figure 3

Dietary intake and non-modifiable factors among different tolvaptan dosing steps. (a) daily protein intake (b) daily sodium intake (c) 24-hour urine volume among genders (d) 24-hour urine volume between 2 age groups (<45 vs. ≥45 years of age) (e) 24-hour urine volume among Mayo classes (f) Spearman correlation of 24-hour urine volume with eGFR. Details concerning the statistical tests can be found in Supplementary Table S1.

Figure 4

Longitudinal assessment of 24-hour urine collection in response to Tolvaptan dosing steps. Longitudinal development of 24-hour urine collection (n = 35) across different tolvaptan dosing steps (a) and per individual patient in relation to osmolality (b). The mean volume is indicated by the red line in (a). The gray color in (b) indicates that no data were available for osmolality.

Figure 5

Quality of life assessed in patients with ADPKD. Using the SF-12 Questionnaire, mental (a) and physical (b) quality of life was assessed for 0 mg (gray) vs. 90/30 mg (blue). A similar analysis was conducted for reported 24-hour urine volume for mental (c) and physical (d) quality of life for 0 mg (gray) vs. 90/30 mg (blue). The size of the dots indicates urine volume increase (%/24h). A normative German sample (available form²¹) is indicated between the green dashed lines.