Objective: To describe the utility of determining plasma cystatin C concentrations in the diagnosis of acute incident kidney injury in septic shock. Patients and methods: Prospective series of 50 patients with septic shock and plasma creatinine levels <2 mg/dL hospitalized in an intensive care unit. Clinical and laboratory follow-ups were conducted, with measurements of cystatin C, urea and plasma creatinine levels from the diagnosis of septic shock to 5 days later. The severity of the septic shock was assessed with the RIFLE scale. Results: Twenty patients (40%) developed acute kidney injury: 8 (16%) were categorized as RIFLE-R, 5 (10%) as RIFLE-I and 7 (14%) as RIFLE-F. All patients categorized as RIFLE-F required extracorporeal renal clearance. Eighteen (36%) patients died, 8 (20%) of whom had developed acute kidney injury in their evolution. There was poor correlation between plasma creatinine and cystatin C levels (r=.501; P=.001), which disappeared upon reaching any degree of renal impairment on the RIFLE scale. Cystatin C levels increased earlier and were better able to identify patients who would develop serious renal function impairment (RIFLE-F) than creatinine and urea levels. The initial cystatin C levels were related to mortality at 30 days (OR=1.16; 95% CI: 03-.85). Conclusions: For patients who developed acute septic kidney injury, the plasma cystatin C levels increased before the classical markers of renal function. Cystatin C also constitutes a severity biomarker that correlates with progression to RIFLE-F, the need for extrarenal clearance and, ultimately, mortality. This precocity could be useful for starting measures that prevent the progression of renal dysfunction. (C) 2014 Elsevier Espana, S.L.U. All rights reserved.