The following is a summary of “Effects of tolvaptan discontinuation in patients with autosomal dominant polycystic kidney disease: a post hoc pooled analysis,” published in the June 2023 issue of Nephrology by Lioudis et al.
Tolvaptan slows kidney function decline in high-risk autosomal dominant polycystic kidney disease (ADPKD) patients. Researchers conducted a pooled analysis to evaluate the effects of discontinuing tolvaptan in ADPKD progression, recognizing that treatment requires a long-term commitment.
They utilized pooled data from two clinical trials of tolvaptan (TEMPO 2:4 [NCT00413777] and TEMPO 3:4 [NCT00428948]), an extension trial (TEMPO 4:4 [NCT01214421]), and an observational study (OVERTURE [NCT01430494]), which enrolled patients from the other tests. Across trials, individual data were linked longitudinally to create analysis cohorts of subjects treated with tolvaptan for >180 days, followed by an observation period of >180 days. For Cohort 1, issues needed ≥2 outcome assessments during the tolvaptan treatment and ≥2 assessments during the follow-up period. Cohort 2 required ≥1 assessment during the tolvaptan treatment and follow-up periods. A piecewise mixed model compared changes in estimated glomerular filtration rate (eGFR) and total kidney volume (TKV) from pre-to-post-treatment periods.
The results showed in Cohort 1 eGFR (n = 20), the annual eGFR change rate (in mL/min/1.73 m2 measured at -3.18 during treatment and -4.33 after treatment, with a non-significant difference (P= 0.16). For Cohort 2 (n =82), the difference between on-treatment (-1.89) and post-treatment (-4.94) conditions was significant (P=0.001). In Cohort 1 (n =11), TKV increased by 5.18% during treatment and 11.69% after treatment (P=0.06); in Cohort 2 (n= 88), the TKV grew by 5.15% during treatment and 8.16% after treatment (P=0.001).
They concluded small sample sizes reveal consistent acceleration in ADPKD progression after tolvaptan discontinuation.
Source: bmcnephrol.biomedcentral.com/articles/10.1186/s12882-023-03247-6
