Objective

Children undergoing cardiac surgery are at high risk for acute kidney injury (AKI). Current diagnosis (serum creatinine change, urine output) lack specificity and sensitivity, especially in new-borns and premature infants. Previous study in an animal model of CPB has shown that post –surgery AKI is associated with elevated levels of platelet MVs indicating their predictive potential. MV and miRNA may provide specific and early-detection markers for AKI and a tool to investigate AKI pathogenesis.

Methods

24 children (≤ 17 yrs), undergoing cardiac surgery with CPB without pre-existing inflammatory state, were recruited. Blood and urine samples were collected at 3 different time-points: pre-op, 6 and 24 hrs. Leukocyte, platelets and MV (derivation, conc. and size distribution) were assessed by flow cytometry and NanoSight. Cytokines (IL-6 and IL-8 and MCP1-3) and NGAL assay were done using ELISA assays. MiRNAs were isolated from plasma and analysed by RT-PCR using Applied Biosystems kits.

Results

AKI was diagnosed in 14 patients and was confirmed by urinary NGAL increase at 6 hours after the operation (25±3.45 ng/ml vs 10.44±2.9 ng/ml; p 0.006). Patients with AKI were younger, underwent longer CPB, received higher volumes of red blood cells, and required higher inotrope support. AKI subjects had increased levels of monocyte and B1-integrin MV. That correlated well with IL-8 and MCP-3 levels and monocyte activation. These changes were also reflected in miRNA profile in both groups.

Conclusion

MV and miRNA could potentially serve as early AKI markers in children and their analysis reveals mechanistic parallels with adults.