Effect modification by chronic kidney disease on renal outcomes in septic shock patients undergoing high-MAP targeting: a secondary analysis of the OPTPRESS trial

The optimal mean arterial pressure (MAP) target for renal protection in septic shock remains unclear. Although higher MAP targets have been suggested to improve renal outcomes in selected patient subgroups, it is unknown whether baseline chronic kidney disease (CKD) modifies the renal response to MAP targeting strategies. We conducted a post hoc secondary analysis of the OPTPRESS trial, a multicenter randomized controlled trial enrolling patients aged ≥ 65 years with septic shock, comparing high-MAP (80–85 mmHg) versus standard-MAP (65–70 mmHg) targets. The primary outcome was renal replacement therapy-free days (RRT-FD) at 28 days, and the secondary outcome was major adverse kidney events (MAKE) at hospital discharge. Multivariable regression models were used to assess the interaction between MAP targeting strategy and documented history of CKD status. Stratified analysis was subsequently performed within CKD and non-CKD subgroups. Sensitivity analysis using inverse probability of treatment weighting (IPTW) and multiple imputation was conducted. Among 431 patients included in the complete case analysis, 70 had CKD and 361 did not. A statistically significant interaction between MAP targeting strategy and CKD status was observed for RRT-FD (p for interaction = 0.040). In adjusted analyses stratified by CKD status, high-MAP targeting was associated with fewer RRT-FD in patients without CKD (adjusted β, − 3.5 days; 95% CI − 5.94 to − 1.11), whereas no significant association was observed in patients with CKD (adjusted β, + 2.0 days; 95% CI − 4.34 to + 8.35). For MAKE, the direction of effect was consistent with that observed for RRT-FD although statistical significance was not reached in patients without CKD. Sensitivity analysis yielded directionally consistent findings. Documented history of CKD may modify the renal response to high-MAP targeting in elderly patients with septic shock. High-MAP targets were associated with fewer RRT-FD in patients without CKD. Given the exploratory and post hoc nature of this analysis, these findings should be interpreted cautiously and warrant confirmation in prospective studies evaluating individualized MAP targets according to baseline renal function in septic shock.