Urinary Proteome Analysis in Patients With Stable SFU Grade 4 Ureteropelvic Junction Obstruction Differs From Normal

Objective To evaluate and analyze the urinary proteome in infants with stable grade 4 ureteropelvic junction obstruction (UPJO) and compare to age-matched normal controls. Methods Bladder urine specimens were obtained from 21 healthy infants with normal maternal/fetal ultrasound and 25 infants with grade 4 unilateral UPJO. All patients had >40% ipsilateral individual kidney function by renal scanning and the anteroposterior (AP) diameter of the hydronephrotic kidney ranged from 1.6-3.9 cms at presentation. Over a 5-year follow-up period, the disease progressed in 7 infants (28%), resolved in 4 (16%), and remains stable in the majority (56%). The urinary specimens were prepared using standard methods and subjected to LC/MS/MS analysis. The normalized data were annotated utilizing the Ingenuity Pathways Analysis (IPA; www.Ingenuity.com ) knowledge platform. Results In the stable UPJO group, the urinary proteomes obtained in infancy differed significantly from the age-matched controls. Analysis revealed important differences in a number of biologic functions including inflammation, apoptosis, tubular injury and fibrosis, and reactive oxygen species response. Conclusion The urinary proteomes from the bladder in patients with stable grade 4 UPJO (by imaging criteria) are significantly different at birth and during the first year of life and seem to indicate the presence of an ongoing active renal response to UPJO. The imminent discovery of surrogate urinary biomarkers may result in reconsideration of the watchful waiting strategy during this critical period of renal maturation and development in infancy.