Transfer of Low-Molecular Weight Single-Stranded DNA through the Membrane of a High-Flux Dialyzer

Abstract

Purpose Microbial contamination is often present in dialysate used for hemodialysis. Small single-stranded bacterial DNA sequences are capable of activating human inflammatory pathways, through mechanisms that include the Toll-like-receptor 9, and dialysis patients frequently show severe inflammation. Since these molecules have been found in dialysate and in patients’ bloodstreams, we studied the potential of low-molecular weight DNA sequences, of the same structure as found in bacteria, to cross from the dialyzer circuit to the blood circuit of a dialysis filter. Methods The mass transfer of DNA fragments across a high-flux dialyzer was evaluated with an in vitro dialysis model, in both conventional dialysis and pure convection mode. Measurement of DNA was performed by HPLC. Results In dialysis mode, these mass transfer coefficients were calculated for different single-stranded DNA chain lengths: 5-bases = 28.5%, 9-bases = 20.5%, 20-bases = 9.4%, 35-bases = 2.4%, 50-bases and 100-bases, no transfer detected. In convection mode, these sieving coefficients were calculated: 5-bases = 1.0, 9-bases = 1.0, 20-bases = 0.68, 35-bases = 0.40, 50-bases = 0.17, 100-bases, no convective transfer detected. The physical size of DNA molecules could be the major factor that influences their movement through dialyzer pores. Conclusions This study establishes that significant transfer across the dialyzer may occur with singlestranded DNA in the size range of 20-bases or less. These findings need to be confirmed with an in vitro whole blood model and with clinical investigations. Previous studies have described the clinical benefits of achieving high-purity dialysate. Precautions are warranted to minimize the presence of these DNA compounds in fluids utilized for hemodialysis treatment.