Identification of Urinary CD44 and Prosaposin as Specific Biomarkers of Urinary Tract Infections in Children With Neurogenic Bladders

Forster, Catherine S; Haffey, Wendy D; Bennett, Michael; Greis, Kenneth D; Devarajan, Prasad

One of the main limitations in this work is the lack of a standardized definition of UTI in patients with neurogenic bladders. There is significant variation in the clinical management of bacteriuria in this patient population, as well as the definition of UTI used in research. 3 Therefore, we have chosen a definition that appears in the literature for use in research, but realize that this is still an imperfect definition. To mitigate some of the potential for misclassification bias, we performed an additional review of the patients' charts to ensure that there was no ambiguity around the classification of either infection or colonization. However, the combination of the definition that we used plus clinical acumen is still imperfect, and thus, the lack of a validated way to differentiate UTI from colonization remains a limitation of this work. Other limitations include the limited number of patients used in both arms of this work, and the inability to better match patients with UTI and UTC in the mass spectrometry arm. Furthermore, we did not perform stability studies on the proteins of interest and are unable to determine whether or not prolonged storage could affect these levels. However, as all urine samples used in this work were stored for the same amount of time, we anticipate this likely did not affect our results of the differentially upregulated proteins. A final limitation is the use of urine creatinine for normalization. We used urine creatinine to standardize the proteins for urine concentration, which may not be the ideal method of standardization in this cohort. Given the differences in body habitus and anthropomorphic measurements in this population, the production of serum creatinine is variable, 50 which directly impacts the utility of urine creatinine as a method of normalization. Therefore, the use of urine creatinine may be confounding our results.