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Effect modification by chronic kidney disease on renal outcomes in septic shock patients undergoing high-MAP
Hiraaki Okuzawa1, Akira Endo2, Tomohiro Akutsu1
1Department of Acute Critical Care Medicine, Tsuchiura Kyodo General Hospital, 4-1-1 Otsuno, Tsuchiura, Ibaraki, Japan.
Insights
Higher mean arterial pressure (MAP) targets in septic shock may harm kidney function in patients without chronic kidney disease (CKD). Baseline CKD may alter the renal response to MAP targeting strategies in elderly patients.
Area of Science:
- Critical Care Medicine
- Nephrology
- Clinical Trials
Background:
- The optimal mean arterial pressure (MAP) target for renal protection in septic shock is not well-defined.
- The influence of pre-existing chronic kidney disease (CKD) on renal outcomes with different MAP targets in septic shock remains unknown.
Purpose of the Study:
- To investigate whether baseline CKD status modifies the renal response to high vs. standard MAP targets in elderly patients with septic shock.
- To analyze the impact of MAP targeting strategies on renal replacement therapy-free days (RRT-FD) and major adverse kidney events (MAKE) in septic shock patients with and without CKD.
Main Methods:
- Post hoc analysis of the OPTPRESS randomized controlled trial involving patients aged ≥65 years with septic shock.
- Comparison of high-MAP (80-85 mmHg) versus standard-MAP (65-70 mmHg) targets.
- Assessment of interaction between MAP target and CKD status on RRT-FD and MAKE using multivariable regression and stratified analyses.
Main Results:
- A significant interaction between MAP targeting strategy and CKD status was found for RRT-FD (p=0.040).
- High-MAP targeting was associated with fewer RRT-FD in patients without CKD (adjusted β = -3.5 days).
- No significant association was observed between high-MAP targeting and RRT-FD in patients with CKD.
Conclusions:
- Baseline CKD may influence the renal response to high-MAP targets in elderly septic shock patients.
- High-MAP targets were linked to poorer renal outcomes (fewer RRT-FD) in non-CKD patients.
- Further prospective studies are needed to confirm these findings and explore individualized MAP targets based on renal function.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
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