We read with great interest the article entitled Uric acid excretion in rotavirus gastro-enteritis by Al-Shibli et al.Citation1 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.Citation2–Citation5 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.Citation1–Citation6 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.Citation1
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.Citation7 It is postulated that the frequency of dysfunctional ABCG2 in Japanese individuals was >50%.Citation8 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
References
- Al-Shibli AAl Tatari HAl Ameri AGhatasheh GIssah MAl Attrach I. Uric acid excretion in rotavirus gastro-enteritis. Paediatr Int Child Health. 2014;34:19–23.
- Fujinaga SKaneko KOhtomo YTakada MKobayashi KTada M. Acute renal failure due to obstructive uric acid stones associated with rotavirus gastroenteritis. Pediatr Nephrol. 2005;20:239–40.
- Morita TAshida AFujieda MHayashi AMaeda AOhta K. Four cases of postrenal renal failure induced by renal stone associated with rotavirus infection. Clin Nephrol. 2010;73:398–402.
- Kaneko KShimo THirabayashi MIto TOkazaki HHarada Y. Cause of uric acid stones in rotavirus-associated gastroenteritis. Pediatr Nephrol. 2010;25:2187–8.
- Morita TFujieda M. Acidosis with hyperuricemia and renal tubular damage in viral gastroenteritis. Pediatr Nephrol. 2011;26:2259–60.
- Kaneko K. Enigma of uric acid stones associated with rotavirus-associated gastroenteritis. Pediatr Nephrol. 2011;26:2261.
- Ichida KMatsuo HTakada TNakayama AMurakami KShimizu T. Decreased extra-renal urate excretion is a common cause of hyperuricemia. Nat Commun. 2012;3:764.
- Matsuo HTakada TIchida KNakamura TNakayama ATakada Y. Identification of ABCG2 dysfunction as a major factor contributing to gout. Nucleosides Nucleotides Nucleic Acids. 2011;30:1098–104.