Usefulness of urinary calprotectin as a novel marker differentiating functional from structural acute kidney injury in the critical care setting

Abstract

Background: Biomarkers are fundamental tools for differentiating between types of acute kidney injury (AKI) and may thus be crucial in management and prognosis. We report on a recently described biomarker, calprotectin, that appears to be a promising candidate in differentiating hypovolemic/functional AKI from intrinsic/structural AKI, whose acknowledgement may play a role in improving outcomes. We aimed to study the efficacy of urinary calprotectin in differentiating these two forms of AKI. The effect of fluid administration on the subsequent clinical course of AKI, its severity and the outcomes were also studied.

Methodology: Children who presented with conditions predisposing to AKI or with diagnosis of AKI were included. Urine samples for calprotectin analysis were collected and stored at - 20 ºC for analysis at the end of the study. Fluids were administered as per clinical conditions, followed by intravenous furosemide 1 mg/kg, and patients were observed closely for at least 72 h. Children with serum creatinine normalization and clinical improvement were classified as with functional AKI, while those with no response were classified as with structural AKI. Urine calprotectin levels between these two groups were compared. Statistical analysis was performed with SPSS 21.0 software.

Results: Of the 56 children enrolled, 26 were classified as with functional AKI and 30 as with structural AKI. Stage 3 AKI was observed in 48.2% of patients and stage 2 AKI in 33.8%. Mean urine output, creatinine and stage of AKI improved with fluid and furosemide or furosemide alone (OR 6.08, 95% CI 1.65-27.23) (p < 0.01). A positive response to fluid challenge was in favor of functional AKI (OR 6.08, 95% CI 1.65-27.23) (p = 0.008). Presence of edema, sepsis and need for dialysis were hallmarks of structural AKI (p < 0.05). Urine calprotectin/creatinine values were 6 times higher in structural AKI compared to functional AKI. Urine calprotectin/creatinine ratio showed the best sensitivity (63.3%) and specificity (80.7%) at a cut-off value of 1 mcg/mL in differentiating the two types of AKI.

Conclusion: Urinary calprotectin is a promising biomarker that may help differentiating structural from functional AKI in children.

Keywords: Acute kidney injury; Functional AKI; Intrinsic AKI; Urinary calprotectin.