Letter to the Editor
Genetic predisposition to hyperuricaemia in rotavirus gastro-enteritis Keywords: Rotavirus, Hyperuricaemia, Uric acid stone, Urate transporter, ABCG2
We read with great interest the article entitled Uric acid excretion in rotavirus gastro-enteritis by Al-Shibli et al.1 and wish to comment on genetic predisposition to hyperuricaemia in children with rotavirus (RV) gastro-enteritis (GE). In 2005, a previously healthy 13-month-old boy was admitted with acute renal failure owing to bilateral obstruction of the pelvic ureteric junctions by uric acid stones associated with RV-GE. It was assumed that the RV-GE caused transient severe hyperuricaemia with increased excretion in combination with low urinary pH and concentrated urine, resulting in obstructive uric acid stone formation. There have been similar reports in other Japanese children.2 – 5 Studies including Al Shibli et al.’s to investigate the underlying conditions predisposing to uric acid stone formation have demonstrated that children with RV-GE had hyperuricaemia with hyperuricosuria and those with GE caused by other viruses did not.1 – 6 In contrast with the findings in Japan, Al-Shibli and colleagues concluded that in Emirati children with RV-GE, uric acid levels and uric acid excretion were not significantly different from those in patients with other presumed viral causes of GE.1 It is well known that the kidney plays an important role in maintaining serum levels of uric acid and that renal urate excretion is determined by the balance between urate secretion and re-absorption. Renal urate is considered to be mainly re-absorbed by two transporters, urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9). However, recent genome-wide association studies have identified the involvement of another important transporter, ATP-binding cassette transporter, sub-family G, member 2 (ABCG2, also known as BCRP) which is expressed on the apical membrane of several tissues including kidney, liver and intestine. Furthermore, it was shown that one-third of urate excretion in humans depends on the extra-renal pathway such as gut excretion via ABCG2, and that decreased extra-renal urate excretion caused by
ABCG2 dysfunction is a common mechanism of hyperuricaemia in the Japanese population.7 It is postulated that the frequency of dysfunctional ABCG2 in Japanese individuals was .50%.8 It seems reasonable therefore to speculate that the disturbed extra-renal excretion of urate owing to genetically determined dysfunctional ABCG2 predisposes Japanese children with RV-GE to hyperuricaemia with hyperuricosuria leading to uric acid stone formation.
Conflicts of interest None to declare Kazunari Kaneko, Takahisa Kimata and Shoji Tsuji
References 1 Al-Shibli A, Al Tatari H, Al Ameri A, Ghatasheh G, Issah M, Al Attrach I, et al. Uric acid excretion in rotavirus gastroenteritis. Paediatr Int Child Health. 2014;34:19–23. 2 Fujinaga S, Kaneko K, Ohtomo Y, Takada M, Kobayashi K, Tada M, et al. Acute renal failure due to obstructive uric acid stones associated with rotavirus gastroenteritis. Pediatr Nephrol. 2005;20:239–40. 3 Morita T, Ashida A, Fujieda M, Hayashi A, Maeda A, Ohta K, et al. Four cases of postrenal renal failure induced by renal stone associated with rotavirus infection. Clin Nephrol. 2010;73:398–402. 4 Kaneko K, Shimo T, Hirabayashi M, Ito T, Okazaki H, Harada Y. Cause of uric acid stones in rotavirus-associated gastroenteritis. Pediatr Nephrol. 2010;25:2187–8. 5 Morita T, Fujieda M. Acidosis with hyperuricemia and renal tubular damage in viral gastroenteritis. Pediatr Nephrol. 2011;26:2259–60. 6 Kaneko K. Enigma of uric acid stones associated with rotavirusassociated gastroenteritis. Pediatr Nephrol. 2011;26:2261. 7 Ichida K, Matsuo H, Takada T, Nakayama A, Murakami K, Shimizu T, et al. Decreased extra-renal urate excretion is a common cause of hyperuricemia. Nat Commun. 2012;3:764. 8 Matsuo H, Takada T, Ichida K, Nakamura T, Nakayama A, Takada Y, et al. Identification of ABCG2 dysfunction as a major factor contributing to gout. Nucleosides Nucleotides Nucleic Acids. 2011;30:1098–104.
Correspondence to: K Kaneko, Department of Pediatrics, Kansai Medical University, 2-5-1 Shin-machi, Hirakata-shi, Osaka 573 1191, Japan. Fax: þ 81 72 804 2758; email: [email protected]
ß W. S. Maney & Son Ltd, 2015
DOI 10.1179/2046905515Y.0000000003
Paediatrics and International Child Health
2015
VOL .
35
NO .
2
165
Copyright of Paediatrics & International Child Health is the property of Maney Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Genetic predisposition to hyperuricaemia in rotavirus gastro-enteritis Keywords: Rotavirus, Hyperuricaemia, Uric acid stone, Urate transporter, ABCG2
We read with great interest the article entitled Uric acid excretion in rotavirus gastro-enteritis by Al-Shibli et al.1 and wish to comment on genetic predisposition to hyperuricaemia in children with rotavirus (RV) gastro-enteritis (GE). In 2005, a previously healthy 13-month-old boy was admitted with acute renal failure owing to bilateral obstruction of the pelvic ureteric junctions by uric acid stones associated with RV-GE. It was assumed that the RV-GE caused transient severe hyperuricaemia with increased excretion in combination with low urinary pH and concentrated urine, resulting in obstructive uric acid stone formation. There have been similar reports in other Japanese children.2 – 5 Studies including Al Shibli et al.’s to investigate the underlying conditions predisposing to uric acid stone formation have demonstrated that children with RV-GE had hyperuricaemia with hyperuricosuria and those with GE caused by other viruses did not.1 – 6 In contrast with the findings in Japan, Al-Shibli and colleagues concluded that in Emirati children with RV-GE, uric acid levels and uric acid excretion were not significantly different from those in patients with other presumed viral causes of GE.1 It is well known that the kidney plays an important role in maintaining serum levels of uric acid and that renal urate excretion is determined by the balance between urate secretion and re-absorption. Renal urate is considered to be mainly re-absorbed by two transporters, urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9). However, recent genome-wide association studies have identified the involvement of another important transporter, ATP-binding cassette transporter, sub-family G, member 2 (ABCG2, also known as BCRP) which is expressed on the apical membrane of several tissues including kidney, liver and intestine. Furthermore, it was shown that one-third of urate excretion in humans depends on the extra-renal pathway such as gut excretion via ABCG2, and that decreased extra-renal urate excretion caused by
ABCG2 dysfunction is a common mechanism of hyperuricaemia in the Japanese population.7 It is postulated that the frequency of dysfunctional ABCG2 in Japanese individuals was .50%.8 It seems reasonable therefore to speculate that the disturbed extra-renal excretion of urate owing to genetically determined dysfunctional ABCG2 predisposes Japanese children with RV-GE to hyperuricaemia with hyperuricosuria leading to uric acid stone formation.
Conflicts of interest None to declare Kazunari Kaneko, Takahisa Kimata and Shoji Tsuji
References 1 Al-Shibli A, Al Tatari H, Al Ameri A, Ghatasheh G, Issah M, Al Attrach I, et al. Uric acid excretion in rotavirus gastroenteritis. Paediatr Int Child Health. 2014;34:19–23. 2 Fujinaga S, Kaneko K, Ohtomo Y, Takada M, Kobayashi K, Tada M, et al. Acute renal failure due to obstructive uric acid stones associated with rotavirus gastroenteritis. Pediatr Nephrol. 2005;20:239–40. 3 Morita T, Ashida A, Fujieda M, Hayashi A, Maeda A, Ohta K, et al. Four cases of postrenal renal failure induced by renal stone associated with rotavirus infection. Clin Nephrol. 2010;73:398–402. 4 Kaneko K, Shimo T, Hirabayashi M, Ito T, Okazaki H, Harada Y. Cause of uric acid stones in rotavirus-associated gastroenteritis. Pediatr Nephrol. 2010;25:2187–8. 5 Morita T, Fujieda M. Acidosis with hyperuricemia and renal tubular damage in viral gastroenteritis. Pediatr Nephrol. 2011;26:2259–60. 6 Kaneko K. Enigma of uric acid stones associated with rotavirusassociated gastroenteritis. Pediatr Nephrol. 2011;26:2261. 7 Ichida K, Matsuo H, Takada T, Nakayama A, Murakami K, Shimizu T, et al. Decreased extra-renal urate excretion is a common cause of hyperuricemia. Nat Commun. 2012;3:764. 8 Matsuo H, Takada T, Ichida K, Nakamura T, Nakayama A, Takada Y, et al. Identification of ABCG2 dysfunction as a major factor contributing to gout. Nucleosides Nucleotides Nucleic Acids. 2011;30:1098–104.
Correspondence to: K Kaneko, Department of Pediatrics, Kansai Medical University, 2-5-1 Shin-machi, Hirakata-shi, Osaka 573 1191, Japan. Fax: þ 81 72 804 2758; email: [email protected]
ß W. S. Maney & Son Ltd, 2015
DOI 10.1179/2046905515Y.0000000003
Paediatrics and International Child Health
2015
VOL .
35
NO .
2
165
Copyright of Paediatrics & International Child Health is the property of Maney Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
