Removal of uremic toxins by renal replacement therapies: a review of current progress and future perspectives

Suguru Yamamoto,Junichiro James Kazama,Takuya Wakamatsu,Ichiei Narita,Yoshimitsu Takahashi,Shin Goto,Yoshikatsu Kaneko

doi:10.1186/s41100-016-0056-9

Suguru Yamamoto, Junichiro James Kazama + Show 5 more

Open Access

https://doi.org/10.1186/s41100-016-0056-9

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Abstract

Accumulation of uremic toxins induces various uremia-related complications in patients with chronic kidney disease, particularly those undergoing dialysis treatment. Direct interactions of uremic toxins with organ tissues are thought to be a major pathophysiological mechanism for disease; for example, indoxyl sulfate reacts directly with macrophages and accelerates atherosclerosis. The removal of sufficient volume of uremic toxins will prevent uremia-related complications in dialysis patients. Hemodialysis with the use of a high-flux dialysis membrane, long or frequent treatment, and increased blood/dialysate flow has improved removal of water-soluble small molecular weight uremic toxins. Middle molecular weight molecules are removed more effectively with hemodialysis using a high-flux membrane, hemodiafiltration and hemofiltration, and a direct hemoperfusion method using β2-microglobulin adsorption column, which is useful in reducing serum β2-microglobulin levels as well as improving dialysis-related amyloidosis-induced clinical symptoms. With improvements in dialysis therapies, removal of low and middle molecular weight water-soluble molecules has improved; however, conventional dialysis treatment is limited in its ability to remove protein-bound uremic toxins (PBUTs). Recent findings suggest that adsorption treatments using oral charcoal adsorbent, mixed matrix membrane hollow fiber, and additive charcoal in the dialysate, in addition to conventional dialysis treatment, may effectively remove a substantial amount of PBUTs. Further improvement of renal replacement therapy, including dialysis and additional therapeutic strategies, is needed for better clearance of small and middle molecular weight molecules and PBUTs, which will lead to improved survival and quality of life for dialysis-dependent chronic kidney disease patients.

Highlights

Patients with chronic kidney disease (CKD), those undergoing dialysis treatment, develop various systemic complications, such as cardiovascular disease, mineral and bone disorders, and infectious disease
Recent findings showed that serum level of trimethylamine-N-oxide (TMAO), molecular weight 75, is increased in hemodialysis patients [7], and clinical research demonstrated an association between serum level of TMAO and cardiovascular disease [8]
indoxyl sulfate (IS) reduced macrophage cholesterol efflux and decreased ATP-binding cassette transporters G1 expression [28]. These results indicate that direct interactions of IS with macrophages may be a major cause of atherosclerosis acceleration in patients with CKD (Fig. 1)

Summary

Background

Patients with chronic kidney disease (CKD), those undergoing dialysis treatment, develop various systemic complications, such as cardiovascular disease, mineral and bone disorders, and infectious disease. Uremic toxins with a small molecular weight are removed with conventional dialysis treatment. Previous clinical studies showed that single-pool Kt/V urea up to 1.8 correlated with improved survival in Japanese hemodialysis patients [10] while high dose hemodialysis with Kt/V urea 1.71 did not show significant benefit for mortality as compared to standard dose of dialysis with Kt/V urea 1.32 [11]. According to those clinical studies, Japanese Society of Dialysis Therapy (JSDT) recommends to keep Kt/V urea more than 1.2 for hemodialysis patients for the better survival [12].

Quantitative analysis of the toxin in biological fluids is possible

Findings

Conclusions