Hydrocortisone Use for Septic Shock in Patients With CKD.

INTRODUCTION

Patients with chronic kidney disease (CKD) are at higher risk of septic shock and mortality than the general population. Although hydrocortisone is often used as an adjuvant therapy for septic shock in the general population to improve clinical outcomes, its effectiveness in patients with CKD remains understudied.

METHODS

We identified a retrospective cohort of patients within TriNetX US collaborative database diagnosed with nondialysis CKD between November 1, 2010 and October 31, 2025 who also developed septic shock. Outcomes of interest within 90 days included all-cause mortality, major adverse kidney events (MAKE) without persistent kidney dysfunction, major adverse cardiovascular or cerebrovascular events (MACCE), mechanical ventilation, hyperglycemia, reinfections, and delirium. Survival analyses and multivariable Cox proportional hazard models were performed.

RESULTS

One to 1, we propensity-score matched 13,141 CKD patients with sepsis treated with hydrocortisone with 13,141 CKD patients with sepsis not treated with hydrocortisone. Our cohort had a mean age of 70 ± 12 years and was 46% female, 21% African American, and 5% Hispanic. Most patients had hypertension (95%), were diabetic (63%), and had ischemic heart disease (68%). Mean serum creatinine concentration was 2.3 ± 2.7 mg/dl, mean lactate concentration was 3 mmol/l, and 25% of patients required mechanical ventilation. In this propensity-score matched analysis, more patients died in the group given hydrocortisone than in the group not given hydrocortisone (4263 [32.4%] vs. 3654 [27.8%]) with adjusted hazard ratio (HR) 1.31 (95% confidence interval [CI]: 1.25-1.36). Hydrocortisone group had higher risk of MAKE HR 1.08 (95% CI: 1.05-1.12), MACCE HR 1.19 (95% CI: 1.15-1.24), and mechanical ventilation HR 1.34 (95% CI: 1.27-1.41) but lower reinfections HR 0.88 (95% CI: 0.85-0.91) and no differences in hyperglycemia HR 1.04 (95% CI: 1.00-1.07) and delirium HR 1.07 (95% CI: 1.00-1.14).

CONCLUSION

In this large, national, multicenter retrospective cohort of patients with CKD and septic shock, use of hydrocortisone was associated with increased risk of mortality, cardiorenal, and pulmonary outcomes, but reduced risk of reinfections. These findings warrant more research to rigorously evaluate the effects of hydrocortisone use in septic shock for this high-risk population.