Uric acid transporter ABCG2 is increased in the intestine of the 5/6 nephrectomy rat model of chronic kidney disease

• Published in: Clinical and experimental nephrology 2014-02, Vol.18 (1), p.50-55
• Main Authors: Yano, Hirofumi, Tamura, Yoshifuru, Kobayashi, Kana, Tanemoto, Masayuki, Uchida, Shunya
• Format: Article
• Language: English
• Subjects: Animals; ATP Binding Cassette Transporter, Sub-Family G, Member 2; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - metabolism; Disease Models, Animal; Ileum - metabolism; Intestinal Elimination; Liver - enzymology; Male; Medicine; Medicine & Public Health; Nephrectomy; Nephrology; Original Article; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; Renal Elimination; Renal Insufficiency, Chronic - etiology; Renal Insufficiency, Chronic - genetics; Renal Insufficiency, Chronic - metabolism; RNA, Messenger - metabolism; Time Factors; Up-Regulation; Urate Oxidase - metabolism; Uric Acid - blood; Uric Acid - metabolism; Uric Acid - urine; Urology
• ISSN: 1342-1751; 1437-7799
• DOI: 10.1007/s10157-013-0806-8

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.