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.
Sun
Phyllis P
PP
Kidney and Dialysis Research Laboratory, Division of Nephrology, Department of Medicine, Caritas St. Elizabeth's Medical Center, Boston, Massachusetts 02135, USA.
Perianayagam
Mary C
MC
Jaber
Bertrand L
BL
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000032:analysis; D002614:Chelating Agents; D003430:Cross-Sectional Studies; D004731:Endotoxins / Q000097:blood* / Q000378:metabolism; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007422:Intestines / Q000382:microbiology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011073:Polyamines / Q000378:metabolism / Q000627:therapeutic use*; D006435:Renal Dialysis; D000069603:Sevelamer
D000893:Anti-Inflammatory Agents; D002614:Chelating Agents; D004731:Endotoxins; D015850:Interleukin-6; D011073:Polyamines; D002097:C-Reactive Protein; D000069603:Sevelamer