ROLE OF CASPOFUNGIN IN RESTORING THE IMPAIRED PHAGOCYTE-DEPENDENT INNATE IMMUNITY IN CHRONIC HAEMODIALYSIS PATIENTS TOWARDS CANDIDA ALBICANS

Phagocyte-dependent cellular immunity in chronic kidney disease patients under haemodialysis treatment is frequently impaired due to the uremic state, resulting in an intrinsic susceptibility to developing invasive fungal infections (IFIs) with high mortality rates. Since synergism between phagocytic cells and antifungal drugs may be crucial for successful therapy, the aim of this study was to evaluate the effects exerted by caspofungin on the functional activities of polymorphonuclear cells (PMNs) in haemodialysed patients (HDs) towards Candida albicans compared to those of PMNs from healthy subjects (HSs). PMNs were separated from venous blood samples of 66 HDs and 30 HSs, as controls, and measurement of phagocytic and intracellular fungicidal activities of HD-PMNs and HS-PMNs was performed in presence of caspofungin at MIC and sub-MIC concentrations. Caspofungin freecontrols were also included. In the drug-free test condition, no significant difference between the phagocytic activity of HD-PMNs and HS-PMNs was detected. On the contrary, a progressive decline in the intracellular killing activity of HD-PMNs against proliferating yeasts was observed. Caspofungin at MIC and sub-MIC levels was able to improve significantly the intracellular fungicidal activity of HD-PMNs against C.albicans, restoring their functionality. Our findings provide evidence that caspofungin exerts a synergistic effect on HD phagocyte cells against C.albicans, being able to strength the depressed intracellular killing PMN activity. These results corroborate the use of caspofungin as effective therapeutic option for IFI treatment in HD patients, in whom even a marginal influence of antifungal drugs on host response may have a relevant effect.