BACKGROUND: Uric acid (UA) remains a risk factor of chronic kidney disease (CKD). Therefore, it is important to clarify the mechanism of UA excretion in CKD. The specific mechanisms of extrarenal excretion from the intestine are unknown. We evaluated the expression of the UA transporter in the intestinal tract--the ATP-binding cassette transporter G2 (ABCG2)--in a 5/6 nephrectomy rat model of CKD. METHODS: Male Wistar rats (6 weeks old) were randomly assigned to the 5/6 nephrectomized (Nx) group or the sham-operated control group. Urine and blood samples were collected every 4 weeks. All the rats were killed at 8 weeks to obtain liver, duodenum, jejunum, ileum, and transverse colon tissues. Uricase activity was measured in the liver. Expression of ABCG2 in intestinal mucosa was measured with real time polymerase chain reaction (PCR). RESULTS: The Nx group showed significantly decreased urine UA excretion/body weight and UA clearance compared to the control group at 4 and 8 weeks after nephrectomy. In contrast, serum UA and uricase activity were not significant. The expression of ABCG2 in the ileum of the Nx group showed significantly increased upregulation, while no changes were seen in the intestines of the control group. CONCLUSIONS: The Nx rats exhibited lower excretion of urine UA and over-expression of ABCG2 in the ileum. The fact that serum UA did not increase despite the decrease in UA excretion suggests that an excretory pathway other than the kidney, probably the intestine, may operate in a complementary role that corroborates the increase in ABCG2 expression in the ileum.
BACKGROUND:Uric acid (UA) remains a risk factor of chronic kidney disease (CKD). Therefore, it is important to clarify the mechanism of UA excretion in CKD. The specific mechanisms of extrarenal excretion from the intestine are unknown. We evaluated the expression of the UA transporter in the intestinal tract--the ATP-binding cassette transporter G2 (ABCG2)--in a 5/6 nephrectomy rat model of CKD. METHODS: Male Wistar rats (6 weeks old) were randomly assigned to the 5/6 nephrectomized (Nx) group or the sham-operated control group. Urine and blood samples were collected every 4 weeks. All the rats were killed at 8 weeks to obtain liver, duodenum, jejunum, ileum, and transverse colon tissues. Uricase activity was measured in the liver. Expression of ABCG2 in intestinal mucosa was measured with real time polymerase chain reaction (PCR). RESULTS: The Nx group showed significantly decreased urine UA excretion/body weight and UA clearance compared to the control group at 4 and 8 weeks after nephrectomy. In contrast, serum UA and uricase activity were not significant. The expression of ABCG2 in the ileum of the Nx group showed significantly increased upregulation, while no changes were seen in the intestines of the control group. CONCLUSIONS: The Nxrats exhibited lower excretion of urine UA and over-expression of ABCG2 in the ileum. The fact that serum UA did not increase despite the decrease in UA excretion suggests that an excretory pathway other than the kidney, probably the intestine, may operate in a complementary role that corroborates the increase in ABCG2 expression in the ileum.
Authors: M Maliepaard; G L Scheffer; I F Faneyte; M A van Gastelen; A C Pijnenborg; A H Schinkel; M J van De Vijver; R J Scheper; J H Schellens Journal: Cancer Res Date: 2001-04-15 Impact factor: 12.701
Authors: Linda H Ficociello; Elizabeth T Rosolowsky; Monika A Niewczas; Nicholas J Maselli; Janice M Weinberg; Ann Aschengrau; John H Eckfeldt; Robert C Stanton; Andrzej T Galecki; Alessandro Doria; James H Warram; Andrzej S Krolewski Journal: Diabetes Care Date: 2010-03-23 Impact factor: 17.152
Authors: Owen M Woodward; Anna Köttgen; Josef Coresh; Eric Boerwinkle; William B Guggino; Michael Köttgen Journal: Proc Natl Acad Sci U S A Date: 2009-06-08 Impact factor: 11.205