Sevelamer carbonate reduces inflammation and endotoxemia in an animal model of uremia.
BACKGROUND
Renal failure is associated with activation of inflammatory response, but the mechanisms behind this observation and potential anti-inflammatory strategies are yet to be defined. Endotoxin (ET) translocation from the intestinal lumen can potentially trigger systemic inflammatory response, and ET binding represents a potential anti-inflammatory strategy in renal failure. The aim of this study was to evaluate the ET-binding capacity of sevelamer carbonate in an animal model of renal failure.


METHODS
Rats were 5/6 nephrectomized to induce uremia (U) and sham-operated rats were allocated to receive normal chow (controls) or a diet with 3% sevelamer carbonate added (+SC) for 60 days. Tumor necrosis factor-α (TNF-α) and ET were measured in plasma on days 7, 30 and 60 in all animals.


RESULTS
Renal failure induced an inflammatory response, since TNF-α levels were undetectable in all control animals in contrast to the uremic group (3.18 ± 0.62, 2.58 ± 0.54 and 1.86 ± 0.47 pg/ml, respectively, on days 7, 30 and 60; p < 0.05 at all time points). Similarly, uremic rats presented an increase in ET levels (0.038 ± 0.007 EU/ml) when compared to sham-operated animals (0.008 ± 0.006 EU/ml; p < 0.05). During the study, TNF-α levels in U + SC rats were significantly lower compared with U-control animals (p < 0.05). Similarly, ET levels in U + SC rats were lower when compared with U-control rats (p < 0.005).


CONCLUSIONS
In conclusion, induction of renal failure triggered inflammation and induced endotoxemia in this experimental model of chronic kidney disease, which were reduced by sevelamer treatment. This data suggests that sevelamer carbonate induces an anti-inflammatory effect in parallel to a reduction in ET.
Hauser
Aline B
AB
Center for Health and Biological Sciences, Pontifícia Universidade Católica do Paraná, Rua Imaculada Conceição 1155, Curitiba, Brazil.
Azevedo
Iuly R F
IR
Gonçalves
Simone
S
Stinghen
Andréa
A
Aita
Carlos
C
Pecoits-Filho
Roberto
R
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D019446:Endotoxemia / Q000517:prevention & control*; D007249:Inflammation / Q000150:complications / Q000188:drug therapy*; D007676:Kidney Failure, Chronic / Q000150:complications; D023421:Models, Animal; D011073:Polyamines / Q000627:therapeutic use*; D051381:Rats; D051436:Renal Insufficiency, Chronic / Q000150:complications; D000069603:Sevelamer; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014511:Uremia / Q000188:drug therapy*
D000893:Anti-Inflammatory Agents; D011073:Polyamines; D014409:Tumor Necrosis Factor-alpha; D000069603:Sevelamer