Our results indicate that the minor CXCR1 +2608 C allele is associated with significantly increased susceptibility to APN in childhood, while the CXCR2 +1208 T allele confers protection from recurrent APN.
For example, genetic alterations that reduce TLR4 function are associated with ABU, while polymorphisms reducing IRF3 or CXCR1 expression are associated with acute pyelonephritis and an increased risk for renal scarring.
Low levels of TLR4 are associated with asymptomatic bacteriuria while low levels of CXCR1 are associated with increased incidence of acute pyelonephritis.
CXCR1 expression was investigated as a factor predisposing to APN, because low CXCR1 expression has been associated with disease susceptibility in mice and disease-prone children.
The area under the curve (AUC) value from the receiver operating characteristic (ROC) curve of D-dimer (0.621, P = 0.046, 95% CI: 0.499-0.743) for prediction of VUR was higher than other inflammatory markers, but was inferior to CRP in predicting APN.
Multivariate analysis revealed that serum albumin level and CRP were the significant risk factors for the development of uroseptic shock from calculous APN.
Receiver operating curve (ROC) analyses showed good diagnostic profiles of NGAL, PCT, CRP, and WBCs for identifying APN [area under the curve (AUC) 0.893, 0.855, 0.879, and 0.654, respectively].
Patients with APN were significantly more likely to have AA genotype of the ICAM-1 rs5498 (1462 A/G) polymorphism (p = 0.04) than children with lower UTIs and the TLR-4Asp299Gly GG genotype (p = 0.002) and G allele (p = 0.006) than healthy controls.
Genotyping was performed in 479 patients with severe acute pyelonephritis (UTI, n = 146), community-acquired pneumonia (CAP, n = 109), intra-abdominal infections (IAI, n = 119), and primary bacteremia (BSI, n = 105) by restriction fragment length polymorphism of the polymerase chain reaction (PCR) product and compared with 104 healthy volunteers.
For example, genetic alterations that reduce TLR4 function are associated with ABU, while polymorphisms reducing IRF3 or CXCR1 expression are associated with acute pyelonephritis and an increased risk for renal scarring.
By modifying specific aspects of the innate immune response to UTI, genetic variation either exaggerates the severity of acute pyelonephritis to include urosepsis and renal scarring or protects against symptomatic disease by suppressing innate immune signaling, as in asymptomatic bacteriuria (ABU).
Statistical analysis revealed that only IL-8 (rs4073, -251A>T) showed significant differences in genotype and allele frequency between the control and APN or ALN cases.
Low levels of TLR4 are associated with asymptomatic bacteriuria while low levels of CXCR1 are associated with increased incidence of acute pyelonephritis.
The studies suggest that distinct molecular defects can cause the clinical entity of acute pyelonephritis with renal scarring, and suggest that the susceptibility to UTI in certain patient groups may have a genetic basis.