A pilot study of circulating DPP3 and renin to identify high-risk phenotypes and mortality in septic shock

Sepsis and septic shock are life-threatening conditions associated with high mortality and limited treatment options. Rapid identification of patients at risk for worse outcomes and/or targeted therapeutics are needed. Elevated levels of renin and dipeptidyl peptidase 3 (DPP3) individually have been associated with increased risk in septic shock, which may reflect an attenuated Angiotensin II response as DPP3 contributes to the metabolism of Angiotensin II. We applied an approach to distinguish both circulating renin and DPP3 concentrations at their clinically relevant threshold values for risk in septic shock patients of ≥ 180 pg/mL and ≥ 40 ng/mL, respectively. This analysis revealed four clinical phenotypes of patients with low risk (low renin/low DPP3), intermediate risk (high renin/low DPP3 or low renin/high DPP3) and those patients with the highest risk (high renin/high DPP3). We conclude that the subclassification of both circulating renin and DPP3 concentrations may better identify those patients at greater risk and inform more optimal treatment approaches.