Urinary cystatin C as an early biomarker of acute kidney injury after open and endovascular abdominal aortic aneurysm repair.

BACKGROUND: Acute kidney injury (AKI) after open repair (OR) and endovascular repair (EVAR) of abdominal aortic aneurysm (AAA) is associated with increased mortality and hospital costs. Early detection of AKI is critical to prevent its progression. Recent findings demonstrate that elevated levels of urinary cystatin C (uCysC) may reflect tubular dysfunction. We prospectively evaluated whether uCysC can detect renal dysfunction earlier than serum creatinine (sCr). METHODS: In a prospective study, 126 consecutive patients (mean age ± SD, 69.1 ± 8.66 years) with AAA (EVAR = 87, OR = 39) were enrolled. sCr and uCysC were measured preoperatively (baseline) and at 6, 24, and 48 hr postoperatively. A final measurement was made on day 5. AKI was defined according to Acute Kidney Injury Network criteria. RESULTS: The incidence of AKI was significantly higher (χ(2) test, P < 0.05) in the OR group (n = 13, 33%) than in the EVAR group (n = 15, 17%). The baseline median (interquartile range) value of uCysC was significantly higher (t-test, P < 0.05) in patients of both groups (OR-EVAR) who developed AKI from those who did not (OR/AKI group: 0.06 [0.02-0.12] mg/L, EVAR/AKI group: 0.08 [0.05-0.11] mg/L versus no-AKI subjects: 0.04 [0.02-0.07] mg/L). Subsequent analysis showed that at 6 hr postoperatively, the patients who developed AKI increased their uCysC levels significantly from baseline (OR/AKI group: 0.58 [0.42-0.70] mg/L, EVAR/AKI group: 0.59 [0.30-1.07] mg/L). The median value of uCysC in AKI patients increased at 24 hr (OR/AKI group: 1.37 [0.78-3.40] mg/L, EVAR/AKI group: 2.11 [0.70-2.42] mg/L) and peaked at 48 hr (OR/AKI group: 6.16 [1.74-10.73] mg/L, EVAR/AKI group: 2.57 [1.21-7.40] mg/L), while no increase was observed among those who did not develop AKI at the same time points (0.06 [0.04-0.14] vs. 0.08 [0.04-0.19] mg/L). The diagnostic accuracy of uCysC at 6 hr post-surgery was excellent (area under the curve - receiver-operating characteristic [AUC-ROC] = 0.968), significantly higher than sCr (AUC-ROC = 0.844) and a cutoff value set at 0.30 mg/L can diagnose AKI with a sensitivity of 85.71% and a specificity of 98.97%. CONCLUSIONS: uCysC is superior to sCr in the early diagnosis of AKI following open and endovascular AAA repair.

Measurement of cystatin C in human urine by particle-enhanced turbidimetric immunoassay on an automated biochemistry analyzer.

BACKGROUND: Cystatin C (CysC), is produced by all the nucleated cells of the human body, is freely filtered by the kidney glomerulus and reabsorbed by the tubules. It is widely accepted that no tubular secretion of CysC occurs. Raised urinary levels are believed to indicate tubular damage. METHODS: We report here the validation of a quantitative assay to measure urinary cystatin C (uCysC) using a commercial CysC kit based on a latex particle-enhanced turbidimetric immunoassay (PETIA), on an automated biochemistry analyzer. The clinical relevance of this assay was tested on several kidney disease patients and a reference range was determined using healthy controls. RESULTS: The assay is precise (total CV<4%), and sensitive (limit of quantification=0.06 mg/dL, and limit of detection=0.02 mg/L). Calibration is stable for at least 30 days. The assay showed very good linearity over the studied interval (0.02 to 2.25mg/L). Recovery ranged from 101.62 to 106.49%. The analyte is stable, at 4°C for at least 2 days, and at 20°C for 48 h. The upper reference value was 0.12 mg/L Median uCysC concentration in 30 acute kidney injury patients (1.47 mg/L, interquartile range=0.27-3.87 mg/L) and was significantly higher than that in 25 patients with normal kidney function (0.05, 0.03-0.12; p<0.0001), 30 patients with chronic kidney disease (0.13, 0.05-0.77; p<0.0001) and 15 patients with pre-renal azotemia (0.15, 0.08-0.31; p<0.0001). CONCLUSION: Our data indicate that uCysC can be processed on automated biochemistry analyzers and its measurement could easily be added to a standard panel to screen kidney diseases.