Appearance of circulating DNA during hemodialysis.

The appearance of circulating DNA during hemodialysis was investigated by use of a modified counterimmunoelectrophoresis assay capable of detecting as little as 0.02 to 0.05 microng of native DNA per milliliter of plasma. It was found that free DNA was regularly released during procedure in widely varying amounts which ranged as high as 5 microng/ml. Both the amount of plasma DNA and its rate of appearance increased progressively throughout the procedure and had no temporal correlation with the transitory early leukopenia that was previously described. Circulation in vitro of fresh blood through a dialysis coil also resulted in the appearance of plasma DNA suggesting that passage of blood through the coil itself can account, at least in part, for circulating DNA, presumably by release from leukocytes. Neither the presence (nor reversal) of the uremic state per se nor removal of inhibitors of the assay during hemodialysis are able to account for the findings. Whether free circulating DNA is of clinical importance is, as yet, unknown. A hypothesis is proposed linking chronic exposure to circulating intracellular materials, including DNA, to the accelerated atherosclerosis recently described as a late complication of hemodialysis. Currently, hemodialysis is the only clinical state known to be characterized by the presence of circulating DNA over long periods of time. Since this phenomenon is iatrogenically induced, further exploration of possible pathogenetic implications seems particularly important.