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We performed a case-control study in children diagnosed by the first episode of upper urinary tract infection with or without vesicoureteral reflux to evaluate the association of functional polymorphism of interleukin-8 (-251AT and +2767AG), and its receptor CXCR1 (+2607GC).Genomic DNA was obtained from 265 children with a clinical and laboratory diagnosis of urinary tract infection who were recruited in northeast Italy. The children were subdivided as 173 who were dimercapto-succinic acid scan positive with positive static renal scintigraphy in acute conditions, consistent with the diagnosis of acute pyelonephritis, and 92 who were dimercapto-succinic acid scan negative. Genetic analysis for the same polymorphisms was also extended to a control population of 106 umbilical cord DNA samples.Statistical analysis of genotype data showed that 1) the tested populations were in Hardy-Weinberg equilibrium, 2) there were significant differences between the dimercapto-succinic acid scan positive and negative groups (p=0.049), and the dimercapto-succinic acid scan positive group vs controls (p=0.032) in terms of interleukin-8 -251AT polymorphism frequency, 3) there was also a significant difference in the distribution of IL-8 -251AT and +2767AG polymorphisms between dimercapto-succinic acid scan positive and negative children in the subgroup without vesicoureteral reflux (p=0.03 and 0.02, respectively) and 4) no significant differences were found in the frequency of the distribution of CXCR1 +2607GC polymorphism in all groups.These data suggest that the gene for the proinflammatory chemokine interleukin-8 is involved in susceptibility to acute pyelonephritis during upper urinary tract infection in children with or without vesicoureteral reflux.

Urinary excretion of the most widely studied renal stone promoting (calcium, oxalate, uric acid and phosphate) and inhibiting (citrate, magnesium, pyrophosphate and glycosaminoglycans) factors, as well as the Tamm-Horsfall mucoprotein, was evaluated in 14 children with idiopathic calcium nephrolithiasis, 6 children with renal stone disease secondary to excretory malformations and 19 normal controls.No statistically significant differences in urinary excretion of promoting and inhibiting factors were found in children with idiopathic calcium nephrolithiasis but the relationship between promoting and inhibiting factors was changed as shown by an abnormal ratio of oxalate/citrate X glycosaminoglycans. This finding suggests that there is an imbalance between promoting and inhibiting factors in children with idiopathic calcium nephrolithiasis, and it is not detected by assay of each single substance.