Table 2.

Multivariable Fine and Gray subdistribution hazard regression of sustained AKI

CharacteristicsHazard Ratio95% CIP Value
Age0.990.98 to 1.020.89
Men1.100.69 to 1.750.69
Race (nonwhite versus white)0.680.29 to 1.600.38
Hypertension1.570.97 to 2.550.07
Baseline PPI exposure (before follow-up time of 2.5 mo)a0.820.40 to 1.670.58
Baseline PPI exposure (after follow-up time of 2.5 mo)a2.851.34 to 6.080.007
Nephrotoxic chemotherapy exposure1.520.95 to 2.440.08
Immune checkpoint inhibitors class
 CTLA4 versus PD11.851.05 to 3.270.21
 PDL1 versus PD11.380.43 to 4.45
 Combined versus PD11.170.26 to 5.23
Baseline eGFR group
 60–90 versus ≥90 ml/min per 1.73 m20.880.51 to 1.530.52
 <60 versus ≥90 ml/min per 1.73 m20.650.31 to1.36
  • In this multivariable model, baseline demographics (age, race, sex), immune checkpoint inhibitor group, and baseline eGFR were selected a priori for inclusion. Additionally, baseline variables with a P value <0.1 in the univariable model (Table 1) were included. Medication exposure was defined by inclusion in the active medication list at the time that immune checkpoint inhibitor therapy began. PD1 inhibitors were used as the reference group for the immune checkpoint inhibitors class comparison in this model because they were associated with the lowest risk of sustained AKI. Normal eGFR ≥90 ml/min per 1.73 m2 was chosen as reference for eGFR groups. Time to first sustained AKI event (n=82) was the outcome. 95% CI, 95% confidence interval, PPI, proton pump inhibitor, CTLA4, cytotoxic T lymphocyte–associated antigen 4; PD1, Programmed cell death protein 1; PDL1, programmed death ligand 1; Combined, ipilimumab (CTLA4) and nivolumab (PD1).

  • a Interaction of PPI and follow-up time P value =0.01. Derived from the main effect of PPI and the interaction effect between PPI and follow-up time.