Abstract: FR-PO694
Defining the Urine Proteome in Boys with Posterior Urethral Valves
Session Information
- Pediatric Nephrology - 1
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1900 Pediatric Nephrology
Authors
- Wang, Xin, Kidney and Urinary Tract Center, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States
- Zhang, Liwen, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
- Becknell, Brian, Kidney and Urinary Tract Center, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States
- Mcleod, Daryl J., Kidney and Urinary Tract Center, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States
Background
Posterior urethral valves (PUV) occur in 1 in 4000 live male births and are a leading cause of pediatric end-stage kidney disease (ESKD). Among patients with PUV, estimated glomerular filtration rate (eGFR) often remains unchanged until late in the disease process due to adequate renal reserve, limiting proactive intervention opportunities. Distinguishing changes in eGFR due to the natural progression of disease vs. modifiable factors is also challenging. Therefore, measures of chronic kidney disease (CKD) progression that are both timely and specific to PUV are critically needed.
Methods
Boys with PUV (cases) and age- and sex-matched healthy children (controls) were recruited from our multispecialty uronephrology clinic and general pediatric clinics, respectively. Urine was obtained through clean catch, catheterization, or urine bag. Urinary proteins from 20 cases and 20 controls were detected using LC/MS/MS. Differential expression analysis identified proteins that varied between cases and controls, and between cases with normal vs. low eGFR. Functional enrichment analysis was profiled to detect specific biological functions. Correlation analyses examined relationships between these proteins and clinical factors, such as eGFR, creatinine, age, and weight.
Results
We identified conserved urine proteins and biological pathways that are dysregulated in cases compared to controls, along with differences in the urinary proteome between cases with normal versus reduced eGFR. Unique subgroups among cases emerged, each characterized by distinctive urine protein profiles and pathways. Cases with low eGFR accumulate angiogenesis-associated proteins, such as AGT, VCAM1, and CDH5, while exhibiting reduced levels of IGFBP7 and L1CAM. Correlation analyses between eGFR and urinary proteins revealed 31 proteins highly correlated in cases, helping to trace the development of obstruction nephropathy.
Conclusion
These results enhance our understanding of kidney injury in PUV and identify potential urine biomarkers for further investigation. The discovery of these markers and pathways could aid in early diagnosis of obstructive nephropathy, providing healthcare providers with tools for proactive intervention and more precise therapeutic strategies.
Funding
- NIDDK Support