IL-6 Dysregulation May Affect Risk of Recurrent Pyelonephritis

Background: Recurrence after UTI occurs in upwards of 30% of patients. Recurrent pyelonephritis is associated with significantly higher rates of renal scarring. While certain risk factors may exist to dictate recurrence, our understanding is limited as to why some patients are more susceptible than others. The aim of our study was to look for possible mechanisms by which one is susceptible to recurrent episodes of pyelonephritis. Methods: Urine was collected at time of febrile UTI. Patients had to have fever of ≥38.0°C (could be self-reported) and either >50,000 CFU/ml of a single organism on urine culture or imaging consistent with pyelonephritis. ELISA was run to look at urine interleukin-6 expression. A biobank of control urine of uninfected, asymptomatic children was also analyzed. Results were normalized to urine creatinine and reported as pg/mg and compared by Mann-Whitney U test. Results: Patients are described in the Table. There was significantly higher urine IL-6 expressed in those with febrile UTI compared to controls. Of those with active febrile UTI, those with a history of prior UTI had significantly lower IL-6 compared to those with a first time UTI. Conclusion: While IL-6 is induced in infection, differences in expression occur in those prone to infection which could be causative or reactive to having had a prior UTI. Investigating this finding further could help understand the susceptibility to recurrent febrile UTI as a result of a dampened cytokine response. Funding: NIDDK Support Patient demographics and IL-6 expression. - Patient cohort (n) Median age [IQR] (years) p-value Median IL-6 [IQR] (pg/mg) p-value Controls (33) Febrile UTI (33) 11.96 [8.47, 15.76] 7.919 [5.572, 14.52] 0.0170 0 [0, 0] 70.1 [ 19.8, 314.0] <0.0001 First febrile UTI (16) Recurrent febrile UTI (17) 7.974 [4.875, 15.06] 7.359 [5.572, 13.83 0.6455 168.6 [48.0, 470.2] 26.1 [0.93, 117.1] 0.0135