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The Role of Liver in Determining Serum Colon-Derived Uremic Solutes.

Lin CJ, Liou TC, Pan CF, Wu PC, Sun FJ, Liu HL, Chen HH, Wu CJ - PLoS ONE (2015)

Bottom Line: An animal model was also used to confirm the two toxin levels in a case of liver fibrosis.A stepwise multiple linear regression analysis also showed that T-PCS was significantly associated with stages of liver cirrhosis after adjusting for other confounding factors (B = -2.29, p = 0.012).Moreover, the serum and urine levels of T-PCS and T-IS were significantly lower in rats with liver failure than in those without (p<0.01, p<0.05 and p<0.01, p<0.05, respectively).

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology and Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan; Mackay Junior College of Medicine, Nursing and Management, Taipei, Taiwan; Institute of Biotechnology, National Taipei University of Technology, Taipei, Taiwan.

ABSTRACT
Evidence has shown that indoxyl sulfate (IS) and p-cresyl sulfate (PCS) may be alternative predictors of clinical outcomes in chronic kidney disease (CKD). Both toxins are derived from the gastrointestinal tract and metabolised in the liver. However, it is unclear whether the liver affects the production of IS and PCS. Here, we explore the association between IS and PCS levels in liver cirrhosis and a CKD-based cohort (N = 115). Liver and kidney function was assessed and classified by a Child-Pugh score (child A-C) and a modified version of the Modification of Diet in Renal Disease (MDRD) equation (Stages 1-4), respectively. An animal model was also used to confirm the two toxin levels in a case of liver fibrosis. In patients with early liver cirrhosis (child A), IS and PCS were significantly associated with CKD stages. In contrast, serum IS and PCS did not significantly change in advanced liver cirrhosis (child C). A stepwise multiple linear regression analysis also showed that T-PCS was significantly associated with stages of liver cirrhosis after adjusting for other confounding factors (B = -2.29, p = 0.012). Moreover, the serum and urine levels of T-PCS and T-IS were significantly lower in rats with liver failure than in those without (p<0.01, p<0.05 and p<0.01, p<0.05, respectively). These results indicated that in addition to the kidneys, the liver was an essential and independent organ in determining serum IS and PCS levels. The production rate of IS and PCS was lower in patients with advanced liver cirrhosis.

No MeSH data available.


Related in: MedlinePlus

Urine levels of protein-bound uremic toxins (A) T-IS, (B) T-PCS in an animal model with liver failure (*:p<0.05) (N = 5).
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pone.0134590.g003: Urine levels of protein-bound uremic toxins (A) T-IS, (B) T-PCS in an animal model with liver failure (*:p<0.05) (N = 5).

Mentions: In order to confirm the effect of the liver on serum protein-bound uremic toxins, an animal model with CBD ligation was used for the study. The liver function of the study group increased dramatically as compared to the control group (AST: 81.2 ±11.4 vs. 804.1 ± 215.6)(ALT: 51.5 ± 18.6 vs. 154.7 ± 47.6). There was a significant reduction of serum T-IS (2.5±0.5 vs. 0.3±0.1 mg/L, p<0.01) (N = 5) concentrations before and three weeks after bile duct ligation (Fig 2A). The T-PCS level was extremely low before and after surgery, and it did not demonstrate a statistically significant change (0.05 ± 0.03 vs. 0.03 ± 0.04 mg/L, p = NS) (N = 5) (Fig 2B). The urine levels of T-IS and T-PCS were also markedly decreased in rats with liver failure (55.4 ± 13.1 vs. 12.2 ± 13.5, 16.9 ± 10.1 vs. 4.9 ± 3.2 mg/L, respectively) (p<0.05) (N = 5) (Fig 3).


The Role of Liver in Determining Serum Colon-Derived Uremic Solutes.

Lin CJ, Liou TC, Pan CF, Wu PC, Sun FJ, Liu HL, Chen HH, Wu CJ - PLoS ONE (2015)

Urine levels of protein-bound uremic toxins (A) T-IS, (B) T-PCS in an animal model with liver failure (*:p<0.05) (N = 5).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4530864&req=5

pone.0134590.g003: Urine levels of protein-bound uremic toxins (A) T-IS, (B) T-PCS in an animal model with liver failure (*:p<0.05) (N = 5).
Mentions: In order to confirm the effect of the liver on serum protein-bound uremic toxins, an animal model with CBD ligation was used for the study. The liver function of the study group increased dramatically as compared to the control group (AST: 81.2 ±11.4 vs. 804.1 ± 215.6)(ALT: 51.5 ± 18.6 vs. 154.7 ± 47.6). There was a significant reduction of serum T-IS (2.5±0.5 vs. 0.3±0.1 mg/L, p<0.01) (N = 5) concentrations before and three weeks after bile duct ligation (Fig 2A). The T-PCS level was extremely low before and after surgery, and it did not demonstrate a statistically significant change (0.05 ± 0.03 vs. 0.03 ± 0.04 mg/L, p = NS) (N = 5) (Fig 2B). The urine levels of T-IS and T-PCS were also markedly decreased in rats with liver failure (55.4 ± 13.1 vs. 12.2 ± 13.5, 16.9 ± 10.1 vs. 4.9 ± 3.2 mg/L, respectively) (p<0.05) (N = 5) (Fig 3).

Bottom Line: An animal model was also used to confirm the two toxin levels in a case of liver fibrosis.A stepwise multiple linear regression analysis also showed that T-PCS was significantly associated with stages of liver cirrhosis after adjusting for other confounding factors (B = -2.29, p = 0.012).Moreover, the serum and urine levels of T-PCS and T-IS were significantly lower in rats with liver failure than in those without (p<0.01, p<0.05 and p<0.01, p<0.05, respectively).

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology and Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan; Mackay Junior College of Medicine, Nursing and Management, Taipei, Taiwan; Institute of Biotechnology, National Taipei University of Technology, Taipei, Taiwan.

ABSTRACT
Evidence has shown that indoxyl sulfate (IS) and p-cresyl sulfate (PCS) may be alternative predictors of clinical outcomes in chronic kidney disease (CKD). Both toxins are derived from the gastrointestinal tract and metabolised in the liver. However, it is unclear whether the liver affects the production of IS and PCS. Here, we explore the association between IS and PCS levels in liver cirrhosis and a CKD-based cohort (N = 115). Liver and kidney function was assessed and classified by a Child-Pugh score (child A-C) and a modified version of the Modification of Diet in Renal Disease (MDRD) equation (Stages 1-4), respectively. An animal model was also used to confirm the two toxin levels in a case of liver fibrosis. In patients with early liver cirrhosis (child A), IS and PCS were significantly associated with CKD stages. In contrast, serum IS and PCS did not significantly change in advanced liver cirrhosis (child C). A stepwise multiple linear regression analysis also showed that T-PCS was significantly associated with stages of liver cirrhosis after adjusting for other confounding factors (B = -2.29, p = 0.012). Moreover, the serum and urine levels of T-PCS and T-IS were significantly lower in rats with liver failure than in those without (p<0.01, p<0.05 and p<0.01, p<0.05, respectively). These results indicated that in addition to the kidneys, the liver was an essential and independent organ in determining serum IS and PCS levels. The production rate of IS and PCS was lower in patients with advanced liver cirrhosis.

No MeSH data available.


Related in: MedlinePlus