Development and Validation of a Cystatin C-based Staging of AKI in Critically Ill Patients

Acute kidney injury (AKI) criteria and staging are based on serum creatinine and urine output, but serum cystatin C performs better at estimating glomerular filtration rate (GFR) in critically ill patients. Accordingly, a cystatin C-based AKI staging system was developed and its performance studied in critically ill patients.

AKI stages according to Kidney Disease: Improving Global Outcomes (KDIGO) creatinine criteria were converted to corresponding cystatin C-based stages using 14-day mortality in 9424 critically ill patients from 3 Swedish hospitals followed for 5.6 years (median interquartile range: 2.8-7.2). Model performance was evaluated using Cox regression on long-term mortality adjusted for age, gender, comorbidities, and unit type. An independent cohort (n = 434) was used for validation.

KDIGO stages corresponded to the following: Stage 1: increase in cystatin C 1.40 to 1.59 times baseline within 7 days or ≥ 0.44 mg/l within 48 hours; Stage 2: 1.60 to 2.09 times baseline; and Stage 3: above 2.10 times baseline or ≥ 2.80 mg/l. Cystatin C-based versus creatinine-based staging identified 11% more AKI and 10% more Stage 3. Patients reclassified to AKI by cystatin C from no AKI had a higher risk of death of 1.36 (1.24-1.49), whereas those reclassified vice versa had a lower risk 0.71 (0.56-0.91). These findings were consistent irrespective of infection status for 30-day mortality. In the validation cohort, reclassification to a higher stage by cystatin C was an independent predictor of increased risk of death.

In critically ill patients, cystatin C-based staging identified more AKI than KDIGO criteria, and these patients had increased short- and long-term mortality.