Fellowship Flannery: Renin and Renal Biomarker Response to Angiotensin II in Patients with Septic Shock

Up to 40-60% of critically ill patients experience acute kidney injury (AKI), most commonly due to septic shock. Angiotensin II is a novel, FDA approved vasopressor used for distributive shock, that may have particular utility in patients with septic shock and AKI. In a subgroup analysis of the trial leading to drug approval, patients with AKI requiring renal replacement therapy had a greater 28-day survival and greater liberation from renal replacement therapy when receiving angiotensin II as compared to placebo. Angiotensin converting enzyme (ACE) has been shown to be altered in septic shock, leading to elevated angiotensin I: angiotensin II ratios, high renin levels, and subsequently, reduced intraglomerular pressure secondary to a relative angiotensin II deficiency. As such, administration of angiotensin II is hypothesized to constrict the efferent arterioles to a greater degree than the afferent system, increase intraglomerular pressure, urine output, and expedite resolution of sepsis-associated kidney injury. We propose characterization of the human response in a suspected high renin phenotype patient population of septic shock receiving angiotensin II as compared to historical controls. Baseline renin, angiotensin II, and angiotensin 1-7 will be measured prior to initiating the drug, followed by collection at 3 hours, 24 hours, 72 hours, and shock resolution. In addition, to test the hypothesis that angiotensin II improves renal function in septic shock, we will also assess serum cystatin C and urine kidney injury molecule-1 response to angiotensin II. This provides pilot data for future work on the renin-angiotensin-aldosterone system in sepsis, as well as mechanistic data in humans regarding a potential therapy for the clinical issue of sepsis-associated acute kidney injury in the setting of shock.