title: Mechanism underlying the low prevalence of pediatric calcium oxalate urolithiasis.
abstract: OBJECTIVE
  Urinary macromolecules in children show stronger inhibition of Ca oxalate crystal growth, aggregation and adhesion than in adults. To investigate the mechanism of Ca oxalate urolithiasis we evaluated the differences in inhibitory activity against oxalate induced renal cell injury between adults and children.
  
  
  METHODS
  Urine samples were collected from healthy men and their sons. The protective effects of urinary macromolecules against oxalate induced injury to Madin-Darby canine kidney cells (ATCC) were examined by lactate dehydrogenase assay and immunostaining. Variations in the relative abundance of proteins involved in stone formation, such as osteopontin and calgranulin B, were analyzed.
  
  
  RESULTS
  The urine of children had significantly higher urinary macromolecule and glycosaminoglycan concentrations than that of adults (p <0.01). Urinary macromolecules inhibited oxalate induced Madin-Darby canine kidney cell injury in a concentration dependent manner and stronger activity was observed in children (p <0.05). TUNEL staining and 8-OHdG immunostaining indicated stronger inhibition of apoptosis and oxidative stress in Madin-Darby canine kidney cells pretreated with pediatric urinary macromolecules (p <0.01). Osteopontin and calgranulin B expression correlated positively (p = 0.03). These proteins showed greater down-regulation in children (p <0.01). Osteopontin expression also correlated positively with lactate dehydrogenase release (p = 0.03).
  
  
  CONCLUSIONS
  A reason for the low prevalence of pediatric urolithiasis is that pediatric urinary macromolecules have stronger inhibitory effects against oxalate induced renal cell injury and oxidative stress induced apoptosis. Furthermore, results suggest that osteopontin and calgranulin B expression is down-regulated in children due to this inhibitory effect and, thus, stone nidus formation is controlled.
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Chikahiro
authors.initials: C
authors.lastname: Momohara
authors.forename: Masao
authors.initials: M
authors.lastname: Tsujihata
authors.forename: Iwao
authors.initials: I
authors.lastname: Yoshioka
authors.forename: Akira
authors.initials: A
authors.lastname: Tsujimura
authors.forename: Norio
authors.initials: N
authors.lastname: Nonomura
authors.forename: Akihiko
authors.initials: A
authors.lastname: Okuyama
mesh_terms: D000328:Adult; D002129:Calcium Oxalate; D040502:Calgranulin B / Q000096:biosynthesis; D002648:Child; D015536:Down-Regulation; D006801:Humans; D046911:Macromolecular Substances / Q000652:urine; D008297:Male; D008875:Middle Aged; D053495:Osteopontin / Q000096:biosynthesis; D018384:Oxidative Stress; D015995:Prevalence; D014545:Urinary Calculi; D052878:Urolithiasis / Q000453:epidemiology / Q000503:physiopathology*
chemical_list: D040502:Calgranulin B; D046911:Macromolecular Substances; D053495:Osteopontin; D002129:Calcium Oxalate