Header

UZH-Logo

Maintenance Infos

Effect of tolvaptan in autosomal dominant polycystic kidney disease by CKD stage: results from the TEMPO 3:4 trial


Torres, V E; Higashihara, E; Devuyst, O; Chapman, A B; Gansevoort, R T; Grantham, J J; Perrone, R D; Ouyang, J; Blais, J D; Czerwiec, F S (2016). Effect of tolvaptan in autosomal dominant polycystic kidney disease by CKD stage: results from the TEMPO 3:4 trial. Clinical Journal of the American Society of Nephrology, 11(5):803-811.

Abstract

Background and objectives The Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes 3:4 study demonstrated a significant beneficial effect of the vasopressin V2 receptor antagonist tolvaptan on rates of kidney growth and eGFR decline in autosomal dominant polycystic kidney disease (ADPKD). This post hoc analysis was performed to reassess the primary and secondary efficacy endpoints by CKD stage at baseline.
Design, setting, participants, & measurements In a phase 3, multicenter, double-blind, placebo-controlled, 3-year trial, 1445 patients with ADPKD (age 18–50 years), with total kidney volume (TKV) ≥750 ml and estimated creatinine clearance ≥60 ml/min, were randomly assigned 2:1 to split-dose tolvaptan (45/15, 60/30, or 90/30 mg daily as tolerated) or placebo. The primary endpoint was annualized rate of TKV change. Secondary endpoints included a composite endpoint of time to multiple composite ADPKD-related events (worsening kidney function, kidney pain, hypertension, and albuminuria) and rate of kidney function decline.
Results Tolvaptan reduced annualized TKV growth by 1.99%, 3.12%, and 2.61% per year (all P<0.001; subgroup–treatment interaction, P=0.17) and eGFR decline by 0.40 in CKD1 (P=0.23), 1.13 in CKD2 (P<0.001) and 1.66 ml/min per 1.73 m2 per year in CKD3 (P<0.001) with a trend for a positive subgroup-treatment interaction (P=0.07) across CKD1, CKD2 and CKD3. ADPKD-related events were less frequent in tolvaptan recipients than in placebo recipients among those with CKD1 (hazard ratio [HR], 0.83; 95% confidence interval [95% CI], 0.70–0.98; P=0.03) and those with CKD 3 (HR, 0.71; 95% CI, 0.57–0.89; P=0.003), but not among those with CKD2 (HR, 1.02; 95% CI, 0.85–1.21; P=0.86). Aquaresis-related adverse events (more frequent in the tolvaptan group) and ADPKD-related adverse events (more frequent in the placebo group) were not associated with CKD stage. Hypernatremia events in tolvaptan-treated patients with CKD3 and plasma aminotransferase elevations in tolvaptan-treated patients across CKD stages 1–3 occurred more frequently than in placebo recipients.
Conclusions This post hoc analysis suggests clinically similar beneficial effects of tolvaptan in ADPKD across CKD stages 1–3.

Abstract

Background and objectives The Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes 3:4 study demonstrated a significant beneficial effect of the vasopressin V2 receptor antagonist tolvaptan on rates of kidney growth and eGFR decline in autosomal dominant polycystic kidney disease (ADPKD). This post hoc analysis was performed to reassess the primary and secondary efficacy endpoints by CKD stage at baseline.
Design, setting, participants, & measurements In a phase 3, multicenter, double-blind, placebo-controlled, 3-year trial, 1445 patients with ADPKD (age 18–50 years), with total kidney volume (TKV) ≥750 ml and estimated creatinine clearance ≥60 ml/min, were randomly assigned 2:1 to split-dose tolvaptan (45/15, 60/30, or 90/30 mg daily as tolerated) or placebo. The primary endpoint was annualized rate of TKV change. Secondary endpoints included a composite endpoint of time to multiple composite ADPKD-related events (worsening kidney function, kidney pain, hypertension, and albuminuria) and rate of kidney function decline.
Results Tolvaptan reduced annualized TKV growth by 1.99%, 3.12%, and 2.61% per year (all P<0.001; subgroup–treatment interaction, P=0.17) and eGFR decline by 0.40 in CKD1 (P=0.23), 1.13 in CKD2 (P<0.001) and 1.66 ml/min per 1.73 m2 per year in CKD3 (P<0.001) with a trend for a positive subgroup-treatment interaction (P=0.07) across CKD1, CKD2 and CKD3. ADPKD-related events were less frequent in tolvaptan recipients than in placebo recipients among those with CKD1 (hazard ratio [HR], 0.83; 95% confidence interval [95% CI], 0.70–0.98; P=0.03) and those with CKD 3 (HR, 0.71; 95% CI, 0.57–0.89; P=0.003), but not among those with CKD2 (HR, 1.02; 95% CI, 0.85–1.21; P=0.86). Aquaresis-related adverse events (more frequent in the tolvaptan group) and ADPKD-related adverse events (more frequent in the placebo group) were not associated with CKD stage. Hypernatremia events in tolvaptan-treated patients with CKD3 and plasma aminotransferase elevations in tolvaptan-treated patients across CKD stages 1–3 occurred more frequently than in placebo recipients.
Conclusions This post hoc analysis suggests clinically similar beneficial effects of tolvaptan in ADPKD across CKD stages 1–3.

Statistics

Citations

16 citations in Web of Science®
12 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

1 download since deposited on 03 Feb 2017
1 download since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2016
Deposited On:03 Feb 2017 11:45
Last Modified:03 Feb 2017 11:45
Publisher:American Society of Nephrology
ISSN:1555-9041
Publisher DOI:https://doi.org/10.2215/CJN.06300615
PubMed ID:26912543

Download

Preview Icon on Download
Content: Published Version
Filetype: PDF - Registered users only
Size: 855kB
View at publisher