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Urinary DKK3 as a predictor of CKD stages in reflux nephropathy in children
Ayşe Seda Pinarbaşi1, Neslihan Günay2, İnayet Güntürk3
1Division of Pediatric Nephrology, Department of Pediatrics, Eskişehir Yunus Emre State Hospital, Eskişehir, Turkiye.
Insights
Urinary Dickkopf-3 (uDKK3) shows potential as a biomarker for advanced chronic kidney disease (CKD) in children with reflux nephropathy. Higher uDKK3 levels correlate with more severe CKD, but its role in early stages requires further investigation.
Area of Science:
- Pediatric Nephrology
- Biomarker Discovery
- Chronic Kidney Disease (CKD)
Background:
- Reflux nephropathy is a significant cause of pediatric CKD.
- Early intervention is crucial for slowing CKD progression.
- Urinary Dickkopf-3 (uDKK3) is a potential biomarker for tubulointerstitial fibrosis, with limited pediatric data.
Purpose of the Study:
- To investigate the role of urinary Dickkopf-3 (uDKK3) levels in predicting CKD stage in children with reflux nephropathy.
- To assess the association between uDKK3, estimated glomerular filtration rate (eGFR), and albuminuria.
- To evaluate the diagnostic performance of uDKK3 for CKD severity.
Main Methods:
- Cross-sectional study of 113 children with CKD stages 1-4 and 28 healthy controls.
- Measurement of uDKK3 concentrations via enzyme-linked immunosorbent assay (ELISA).
- Correlation analysis with eGFR and albuminuria; Receiver Operating Characteristic (ROC) curve analysis.
Main Results:
- Significantly higher uDKK3 levels in advanced CKD stages (3-4) compared to early stages (1-2) and controls.
- Strong negative correlation between uDKK3 and eGFR; positive correlation with albuminuria.
- ROC analysis for uDKK3/urinary creatinine ratio (uDKK3/uCr) showed an AUC of 0.77, with 71.1% sensitivity and 71.4% specificity.
Conclusions:
- The uDKK3/uCr ratio may serve as a noninvasive biomarker for assessing pediatric CKD severity in reflux nephropathy.
- uDKK3 utility in identifying early-stage CKD was not clearly demonstrated.
- Further large-scale prospective studies are needed to confirm the clinical applicability and prognostic value of uDKK3 in pediatric CKD.
Background/Aim:
Reflux nephropathy is an important cause of chronic kidney disease (CKD) in children. The search for new biomarkers continues, as early intervention is important to slow the progression of CKD. Urinary Dickkopf-3 (uDKK3), a potential marker of tubulointerstitial fibrosis, has been studied in adults but not extensively in children with CKD. This study was conducted to determine the role of uDKK3 levels in predicting the CKD stage in children with reflux nephropathy.
Materials And Methods:
This cross-sectional study included 113 children with CKD stages 1-4 with reflux nephropathy and 28 healthy controls. uDKK3 concentrations were measured using enzyme-linked immunosorbent assay. The association between uDKK3, the estimated glomerular filtration rate (eGFR), and albuminuria was investigated. Receiver operating characteristic (ROC) curves were used to assess diagnostic performance.
Results:
uDKK3 levels were significantly higher in CKD stages 3 and 4 compared to stages 1 and 2 and the control group. A strong negative correlation was observed between uDKK3 and the eGFR, while a positive correlation was noted with albuminuria. ROC analysis revealed an area under the curve (AUC) of 0.77 for the uDKK3 to urinary Cr (uCr) ratio (uDKK3/uCr), with a sensitivity of 71.1% and a specificity of 71.4% at a cutoff value of 1675.48 pg/mg.
Conclusion:
The correlation between the uDKK3/uCr and CKD severity suggests that uDKK3 may serve as a potential noninvasive biomarker for assessing disease severity. However, its utility for identifying early-stage CKD could not be clearly demonstrated in this cohort. uDKK3 appears to be particularly associated with advanced CKD stages, and further large-scale prospective studies are needed to clarify its clinical applicability and prognostic value in pediatric CKD.
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