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C-Terminal Agrin Fragment (CAF) Reflects Renal Function in Patients Suffering from Severe Sepsis or Septic Shock by Michael Drey, Michael Behnes, Robert Kob, Dominic Lepiorz, Stefan Hettwer, Cornelius Bollheimer, Cornel C. Sieber, Thomas Bertsch, Ursula Hoffmann

Background: One of the main causes of acute kidney injury (AKI) in patients treated on an intensive care unit (ICU) is sepsis. The identification of new biomarkers indicating the early development and future course of AKI are of utmost medical interest. The C-terminal agrin fragment (CAF) is measurable in blood serum and might reflect kidney function. Therefore, this study evaluates CAF in patients presenting to an internal ICU with severe sepsis or septic shock. Serum levels of CAF are correlated with biomarkers of kidney function, markers of systemic inflammation, and the presence of AKI and renal replacement therapy (RRT).
Methods: 61 patients suffering from severe sepsis or septic shock were included during the first 24 hours of ICU treatment and blood samples for biomarker measurements, i.e., CAF, creatinine, cystatin C, procalcitonin (PCT), interleukin 6, C reactive protein (CRP), and white blood cells (WBC) were collected on the first day of intensive care treatment. The number of RRT days and the incidence of AKI were documented.
Results: 13% of the patients (8/61) suffered from SIRS/sepsis, 20% (12/61) from severe sepsis, and 67% (41/61) from septic shock. Serum levels of CAF significantly correlated with creatinine (r = 0.623, p < 0.001) and cystatin C (r = 0.578, p < 0.001). Multiple linear regression analyses adjusting CAF for inflammatory parameters (i.e., WBC, CRP, interleukin 6, PCT), age, and gender showed a strong correlation between CAF and creatinine (r = 0.643, p < 0.001). Serum levels of CAF were significantly associated with the need of RRT (area under the curve (AUC) = 0.772, 95% CI: 0.641 - 0.903, p = 0.002) and the incidence of AKI (AUC = 0.721, 95% CI: 591 - 0.850, p = 0.004) as indicated by ROC analysis.
Conclusions: In patients suffering from severe sepsis and septic shock, serum levels of CAF were significantly associated with kidney function and RRT and were not influenced by severe septic conditions.

DOI: 10.7754/Clin.Lab.2014.140724