Sevelamer Hydrochloride Use and Circulating Endotoxin in Hemodialysis Patients: A Pilot Cross-Sectional Study

Objective

There is a growing interest in the potential anti-inflammatory properties of sevelamer hydrochloride, a commonly used phosphate binder for patients with chronic kidney failure. This study explores the hypothesis that sevelamer hydrochloride binds bacterial endotoxin in the intestinal tract, leading to lower circulating endotoxin levels, and offering a novel anti-inflammatory mechanism.

Methods

We performed a cross-sectional study in medically stable patients with chronic kidney failure undergoing maintenance hemodialysis. Blood samples were collected before 2 consecutive dialysis sessions, and plasma was tested for endotoxin, interleukin-6 and C-reactive protein. Linear regression analyses were used to examine patient-related and dialysis-related factors associated with plasma endotoxin level.

Results

Forty-six patients met our eligibility criteria. Their mean age was 62 years, 41% were diabetic, and 65% reported the use of sevelamer hydrochloride. The mean plasma endotoxin level was significantly lower in patients using sevelamer hydrochloride compared with those who were not (0.23 ± 0.01 vs. 0.30 ± 0.01 EU/mL, P = .001). However, plasma interleukin-6 and C-reactive protein levels were not significantly different between the two groups. According to multivariate analysis, the use of sevelamer hydrochloride was associated with a lower plasma endotoxin level after adjustment for race, gender, age, dialysis vintage, total cholesterol level, and white blood cell count.

Conclusions

This proof-of-concept pilot study demonstrates that the use of sevelamer hydrochloride is associated with a lower plasma endotoxin level, supporting the hypothesis that this agent binds to endotoxin in the intestinal lumen. Although this may be an important mechanism by which sevelamer hydrochloride attenuates systemic inflammation, a clinical trial is required to test this hypothesis.