 |
||||
| 2007 JASN IMPACT FACTOR 7.111 | HOME AUTHOR INFO EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP | |||
| CURRENT ISSUE | ARCHIVES | JASN Express | ONLINE SUBMISSION | |
|
||||
| 2007 JASN IMPACT FACTOR 7.111 | HOME AUTHOR INFO EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP | |||
| CURRENT ISSUE | ARCHIVES | JASN Express | ONLINE SUBMISSION | |
CLINICAL SCIENCE |
*Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan; Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan; Department of Cardiovascular Medicine, Tottori University, Yonago, Japan; and Department of Clinical Preventive Medicine, Nagoya University School of Medicine, Nagoya, Japan.
Correspondence to Kimiyoshi Ichida, Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, 3–25–8 Nishishimbashi, Minato-ku, Tokyo 105–8461, Japan. Phone: 81-33433-1111 ext. 3221; Fax: 81-33433-4297;
ABSTRACT. Renal hypouricemia is an inherited and heterogeneous disorder characterized by increased urate clearance (CUA). The authors recently established that urate was reabsorbed via URAT1 on the tubular apical membrane and that mutations in SLC22A12 encoding URAT1 cause renal hypouricemia. This study was undertaken to elucidate and correlate clinical and genetic features of renal hypouricemia. The SLC22A12 gene was sequenced in 32 unrelated idiopathic renal hypouricemia patients, and the relationships of serum urate levels, and CUA/creatinine clearance (Ccr) to SLC22A12 genotype were examined. Uricosuric (probenecid and benzbromarone) and anti-uricosuric drug (pyrazinamide) loading tests were also performed in some patients. Three patients had exercise-induced acute renal failure (9.4%), and four patients had urolithiasis (12.5%). The authors identified eight new mutations and two previously reported mutations that result in loss of function. Thirty patients had SLC22A12 mutations; 24 homozygotes and compound heterozygotes, and 6 heterozygotes. Mutation G774A dominated SLC22A12 mutations (74.1% in 54 alleles). Serum urate levels were significantly lower and CUA/Ccr was significantly higher in heterozygotes compared with healthy subjects; these changes were even more significant in homozygotes and compound heterozygotes. These CUA/Ccr relations demonstrated a gene dosage effect that corresponds with the difference in serum urate levels. In contrast to healthy subjects, the CUA/Ccr of patients with homozygous and compound heterozygous SLC22A12 mutations was unaffected by pyrazinamide, benzbromarone, and probenecid. The findings indicate that SLC22A12 was responsible for most renal hypouricemia and that URAT1 is the primary reabsorptive urate transporter, targeted by pyrazinamide, benzbromarone, and probenecid in vivo. E-mail: ichida@jikei.ac.jp
This article has been cited by other articles:
 |
|
 |
|
  N. Anzai, K. Ichida, P. Jutabha, T. Kimura, E. Babu, C. J. Jin, S. Srivastava, K. Kitamura, I. Hisatome, H. Endou, et al. Plasma Urate Level Is Directly Regulated by a Voltage-driven Urate Efflux Transporter URATv1 (SLC2A9) in Humans J. Biol. Chem., October 3, 2008; 283(40): 26834 - 26838. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T. Le, M. Shafiu, W. Mu, and R. J. Johnson SLC2A9--a fructose transporter identified as a novel uric acid transporter Nephrol. Dial. Transplant., September 1, 2008; 23(9): 2746 - 2749. [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Eraly, V. Vallon, T. Rieg, J. A. Gangoiti, W. R. Wikoff, G. Siuzdak, B. A. Barshop, and S. K. Nigam Multiple organic anion transporters contribute to net renal excretion of uric acid Physiol Genomics, April 1, 2008; 33(2): 180 - 192. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Kikuchi, H. Kusuhara, N. Hattori, I. Kim, K. Shiota, F. J. Gonzalez, and Y. Sugiyama Regulation of Tissue-Specific Expression of the Human and Mouse Urate Transporter 1 Gene by Hepatocyte Nuclear Factor 1 {alpha}/beta and DNA Methylation Mol. Pharmacol., December 1, 2007; 72(6): 1619 - 1625. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J Vazquez-Mellado, V Alvarado-Romano, R Burgos-Vargas, A L Jimenez-Vaca, G Pozo-Molina, and S A Cuevas-Covarrubias Homozygous frameshift mutation in the SLC22A12 gene in a patient with primary gout and high levels of serum uric acid J. Clin. Pathol., August 1, 2007; 60(8): 947 - 948. [Full Text] [PDF]
|
|
|
|
 |
|
 R. Cunningham, M. Brazie, S. Kanumuru, X. E, R. Biswas, F. Wang, D. Steplock, J. B. Wade, N. Anzai, H. Endou, et al. Sodium-Hydrogen Exchanger Regulatory Factor-1 Interacts with Mouse Urate Transporter 1 to Regulate Renal Proximal Tubule Uric Acid Transport J. Am. Soc. Nephrol., May 1, 2007; 18(5): 1419 - 1425. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Hagos, D. Stein, B. Ugele, G. Burckhardt, and A. Bahn Human Renal Organic Anion Transporter 4 Operates as an Asymmetric Urate Transporter J. Am. Soc. Nephrol., February 1, 2007; 18(2): 430 - 439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Vazquez-Mellado, A. L. Jimenez-Vaca, S. Cuevas-Covarrubias, V. Alvarado-Romano, G. Pozo-Molina, and R. Burgos-Vargas Molecular analysis of the SLC22A12 (URAT1) gene in patients with primary gout Rheumatology, February 1, 2007; 46(2): 215 - 219. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Iwanaga, M. Sato, T. Maeda, T. Ogihara, and I. Tamai Concentration-Dependent Mode of Interaction of Angiotensin II Receptor Blockers with Uric Acid Transporter J. Pharmacol. Exp. Ther., January 1, 2007; 320(1): 211 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Yamamoto, H. Yamamoto, K. Ichida, J. Mitome, Y. Tanno, N. Katoh, K. Yokoyama, and T. Hosoya Successful living-related kidney transplantation in hereditary renal hypouricaemia Nephrol. Dial. Transplant., July 1, 2006; 21(7): 2041 - 2041. [Full Text] [PDF]
|
|
|
|
|
|
K. L. Price, Y. Y. Sautin, D. A. Long, L. Zhang, H. Miyazaki, W. Mu, H. Endou, and R. J. Johnson Human Vascular Smooth Muscle Cells Express a Urate Transporter J. Am. Soc. Nephrol., July 1, 2006; 17(7): 1791 - 1795. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Sekine, H. Miyazaki, and H. Endou Molecular physiology of renal organic anion transporters Am J Physiol Renal Physiol, February 1, 2006; 290(2): F251 - F261. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. K. Choi, D. B. Mount, and A. M. Reginato Pathogenesis of Gout Ann Intern Med, October 4, 2005; 143(7): 499 - 516. [Full Text] [PDF]
|
|
|
|
|
|
I. Ishikawa, M. Nakagawa, S. Hayama, S. Yoshida, and T. Date Acute renal failure with severe loin pain and patchy renal ischaemia after anaerobic exercise (ALPE) (exercise-induced acute renal failure) in a father and child with URAT1 mutations beyond the W258X mutation Nephrol. Dial. Transplant., May 1, 2005; 20(5): 1015 - 1015. [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Hediger, R. J Johnson, H. Miyazaki, and H. Endou Molecular Physiology of Urate Transport Physiology, April 1, 2005; 20(2): 125 - 133. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Wakida, D. G. Tuyen, M. Adachi, T. Miyoshi, H. Nonoguchi, T. Oka, O. Ueda, M. Tazawa, S. Kurihara, Y. Yoneta, et al. Mutations in Human Urate Transporter 1 Gene in Presecretory Reabsorption Defect Type of Familial Renal Hypouricemia J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2169 - 2174. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Anzai, H. Miyazaki, R. Noshiro, S. Khamdang, A. Chairoungdua, H.-J. Shin, A. Enomoto, S. Sakamoto, T. Hirata, K. Tomita, et al. The Multivalent PDZ Domain-containing Protein PDZK1 Regulates Transport Activity of Renal Urate-Anion Exchanger URAT1 via Its C Terminus J. Biol. Chem., October 29, 2004; 279(44): 45942 - 45950. [Abstract] [Full Text] [PDF]
|
|
|
HOME
CURRENT ISSUE
ARCHIVES
JASN Express
ONLINE SUBMISSION
AUTHOR INFO
EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP |
Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673
