Hemoadsorption Combined with Hemodialysis and the “Inflammation Mitigation Hypothesis”

Abstract

ABSTRACT Clinical outcomes are still unsatisfactory in patients undergoing chronic maintenance dialysis. Signs and symptoms of uremic intoxication are often present even in presence of an adequate dialysis delivery. These along with cardiovascular and skeletal complications, have been correlated to the accumulation of inflammatory chemical mediators, beta-2 microglobulin (β2M), parathyroid hormone (PTH) and other middle to large molecular weight toxins that are insufficiently cleared by current dialysis techniques. Such condition determines a vicious loop where a subclinical status of inflammation causes a disruption of the immunological response affecting outcomes by accelerated atherosclerosis, anemia, and frequent infections. The overall picture can be described as a systemic inflammatory syndrome with simultaneous activation of the innate and the adaptive immunity. In such condition, new options and techniques are required to achieve a more effective blood purification and to correct the altered immuno-homeostasis. New efficient and biocompatible sorbents are today available (HA 130 Cartridge, Jafron Medical, Zhuhai, China) and they can be advantageously coupled in series with the hemodialyzer to perform hemoadsorption combined with hemodialysis (HA-HD). This technique has been already studied in at least two randomized trials demonstrating an effective improvement of clinical and biochemical outcomes. We have calculated the kinetics of β2M in a single session, in a series of three consecutive sessions of a week and in a period of three months using different frequencies of application (first month: Three sessions per week; second month: Two sessions per week; third month: One session per week). In the single session the reduction ratio was superior to other techniques such as hemodialysis (HD), high-flux hemodialysis (HFD) or hemodiafiltration (HDF). In the thrice weekly regime, the time average concentration (TAC) of β2M resulted inferior to HD and HDF. In the long period, a lower concentration of β2M was maintained even with a once-a-week regime. Considering the parallel reduction of inflammatory parameters, we could hypothesize that the enhanced removal of uremic toxins and chemical mediators led to a mitigation of the systemic inflammation with a progressive reduction in the generation of β2M. This “inflammation mitigation hypothesis (IMH)” supports the prescription of HA-HD once a week, possibly after a month of thrice weekly regime.