Table 5.

Subjects with alanine transaminase elevations >2× and >3× upper limit of normal by statin and allopurinol use

Statin/Allopurinol CouseALT ElevationsTEMPO 3:4REPRISE
Tolvaptan n (%)Placebo n (%)Difference in Proportions % (95% CI)Total n (%)Tolvaptan n (%)Placebo n (%)Difference in Proportions % (95% CI)Total n (%)
With statins13468202204202406
>2×ULN11 (8.2)3 (4.4)3.8 (−2.9 to 10.5)14 (6.9)14 (6.9)6 (3.0)3.9 (−0.3 to 8.1)20 (4.9)
>3×ULN6 (4.5)2 (2.9)1.5 (−3.8 to 6.9)8 (4.0)10 (4.9)3 (1.5)3.4 (0.0 to 6.8)13 (3.2)
With statins but not allopurinol11661177160160320
>2×ULN8 (6.9)3 (4.9)2.0 (−5.1 to 9.1)11 (6.2)9 (5.6)5 (3.1)2.5 (−2.0 to 7.0)14 (4.4)
>3×ULN4 (3.4)2 (3.3)0.2 (−5.4 to 5.7)6 (3.4)5 (3.1)2 (1.3)1.9 (−1.3 to 5.1)7 (2.2)
With allopurinol but not statins5118695757114
>2×ULN8 (15.7)2 (11.1)4.6 (−13.0 to 22.2)10 (14.5)4 (7.0)1 (1.8)5.3 (−2.2 to 12.7)5 (4.4)
>3×ULN3 (5.9)2 (11.1)−5.2 (−21.1 to 10.7)5 (7.2)2 (3.5)03.5 (−1.3 to 8.3)2 (1.8)
With neither allopurinol nor statins7763971173420426846
>2×ULN60 (7.7)9 (2.3)5.5 (3.1 to 7.8)69 (5.9)36 (8.6)8 (1.9)6.7 (3.7 to 9.7)44 (5.2)
>3×ULN30 (3.9)1 (0.3)3.6 (2.2 to 5.1)31 (2.6)26 (6.2)5 (1.2)5.0 (2.5 to 7.5)31 (3.7)
  • Data are on the basis of laboratory values and not adverse event reporting as in Tables 3 and 4. ALT, alanine transaminase; TEMPO 3:4, Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes 3:4 trial; REPRISE, Replicating Evidence of Preserved Renal Function: an Investigation of Tolvaptan Safety and Efficacy in ADPKD trial; 95% CI, 95% confidence interval; ULN, upper limit of normal.