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Urinary biomarkers in obstructive nephropathy
Peter Trnka1, Larissa Ivanova, Michael J Hiatt
1Department of Paediatrics and Child Health, University of Queensland, Brisbane, Australia.
Insights
Urinary biomarkers like TGFβ and L1CAM can help assess kidney function in children with obstructive nephropathy, aiding in the prediction of chronic kidney disease progression.
Area of Science:
- Pediatric Nephrology
- Biomarker Discovery
- Renal Physiology
Background:
- Obstructive nephropathy is a primary cause of chronic kidney disease (CKD) in children.
- Assessing the severity of renal impairment and predicting progression to renal failure in these children is challenging.
Purpose of the Study:
- To evaluate candidate urinary biomarkers for assessing renal impairment in children with posterior urethral valves (PUVs).
- To determine the correlation of these biomarkers with glomerular filtration rate (GFR).
Main Methods:
- A case-control study involving 27 children with PUVs and 20 age-matched controls.
- Measurement of urinary biomarkers, including protein-to-creatinine ratio, aquaporin-2, TGFβ, and L1CAM.
- Correlation analysis with GFR using receiver-operating characteristic (ROC) curves and regression analyses.
Main Results:
- Children with PUVs showed higher urinary protein-to-creatinine ratios and altered excretion of aquaporin-2, TGFβ, and L1CAM compared to controls.
- Urinary TGFβ excretion was inversely correlated with GFR.
- TGFβ, L1CAM, and protein-to-creatinine ratio demonstrated good performance in identifying low GFR.
Conclusions:
- Candidate biomarkers are measurable in whole urine and urine exosomes.
- These biomarkers correlate with GFR in boys with PUVs, offering potential for improved assessment of obstructive nephropathy.
Background And Objectives:
Obstructive nephropathy is a leading cause of CKD in children. The assessment of severity of renal impairment and the prediction of which children will progress to renal failure are, however, challenging.
Design, Setting, Participants, & Measurements:
This case-control study measured the urinary excretion of candidate biomarkers in 27 prevalent case-patients with posterior urethral valves (PUVs) and 20 age-matched controls, correlated their urinary concentration with GFR, and analyzed receiver-operating characteristic (ROC) curve and regression analyses to assess their performance as tests for low GFR.
Results:
The median urinary protein-to-creatinine ratio was higher in children with PUV (45 g/mol; range, 5-361 g/mol) than in controls (7 g/mol; range, 3-43 g/mol) (P<0.01) and correlated inversely with renal function (r = -0.44; P<0.05). In whole urine, excretion of aquaporin-2 was significantly decreased, whereas that of TGFβ and L1 cell adhesion molecule (L1CAM) was significantly increased. Whole-urine TGFβ excretion correlated inversely with GFR (r = -0.53; P<0.05). As tests for low GFR, whole-urine TGFβ, L1CAM, and urinary protein-to-creatinine ratio performed best, with areas under the ROC curves of 0.788, 0.795, and 0.814, respectively. By linear regression analysis, whole-urine TGFβ, L1CAM, and urinary protein-to-creatinine ratio were associated with low GFR in the case-patients.
Conclusions:
Candidate biomarkers of obstructive nephropathy can be readily measured in whole urine and in urine exosomes. In boys with PUV, these biomarkers correlate with GFR.
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