Subtle change of cystatin C, with or without acute kidney injury, associated with increased mortality in the intensive care unit

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Recent epidemiologic studies suggest a significant association between small increases in serum creatinine (sCr) and adverse outcomes. The Acute Kidney Injury Network (AKIN) sought to increase the sensitivity of the AKIN criteria for acute kidney injury (AKI) by recommending the use of small changes in sCr for the diagnosis of AKI. Several recent studies have reported that serum cystatin C (cysC) is more accurate than sCr as a surrogate for the glomerular filtration rate. This study was performed to determine whether small increases in cysC (≥0.3 mg/L within 48 hours) are associated with clinical outcomes in critically ill patients.

Materials and Methods:

This was a prospective study of 274 consecutive patients admitted to the intensive care unit. Clinical data, including urine output, sCr, cysC, and outcomes, were collected for up to 3 months. Kaplan-Meier curves were used to determine the 90-day survival rate. Mortality was adjusted according to the Cox proportional hazards model.


Acute kidney injury developed in 84 (30.7%) patients based on the AKIN criteria. Among these patients, 42 (50%) had stage 1; 8 (9.5%), stage 2; and 34 (40.4%), stage 3 disease. Fourteen patients with increased cysC did not have AKI by AKIN criteria. The overall 90-day mortality was 20.8%. When mortality was stratified by group, it was 5.7% for the no-AKI-without-cysC-increment group, 28.6% for the no-AKI-with-increased-cysC group, 33.3% for the AKIN stage 1 group, 62.5% for the AKIN stage 2 group, and 70.6% for the AKIN stage 3 group (P < .001). Kaplan-Meier curves were constructed for each group based on stage and 90-day survival. The Cox analysis showed that patients who met AKIN criteria and patients with increases of cysC without AKI had associated mortality. In addition, patients with increases in cysC without AKI had outcomes similar to the patients with stage 1 AKI.


Small increases of cysC were associated with increased mortality in intensive care unit patients independent of diagnosis of AKI by AKIN criteria.

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