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Urinary biomarkers as point-of-care tests for predicting progressive deterioration of kidney function in congenital anomalies of kidney and urinary tract: trefoil family factors (TFFs) as the emerging biomarkers

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Abstract

Background

Children with congenital anomalies of kidney and urinary tract (CAKUT) are at high risk of progressive deterioration of kidney function and further developing stage 5 chronic kidney disease (CKD 5), even after a successful surgery. This prospective study was designed to determine whether urinary biomarkers can predict progressive deterioration of kidney function in children with CAKUT.

Methods

The study included 50 consecutive children, aged < 14 years, who were diagnosed with congenital uropathies (PUV, VUR, and PUJO) and 20 age-matched controls. Examination of four urinary biomarkers, i.e., trefoil family factors (TFF) 1 and 3, neutrophil gelatinase–associated lipocalin (NGAL) and microalbuminuria (MALB) was done at the beginning of follow-up. Kidney function was assessed, at the beginning and after 12-months of follow-up, by technetium-99m diethylene triamine pentaacetic acid (DTPA) and technetium-99m dimercaptosuccinic acid (DMSA) scans. Progressive deterioration in the kidney function was defined as a fall in the GFR from ≥ 60 to < 60 ml/min/1.73 m2 on comparing the baseline and latest DTPA scans; and/or new-onset cortical scar/scars or increase in the size of previous scar/scars on serial DMSA scans. Group 1 and group 2 included children without and with progressive functional deterioration respectively.

Results

The median (IQR) age of children with CAKUT and controls was 3 (1.5–5) and 2.3 (1.2–3.6) years, respectively, and showed no significant difference (p = 0.29). Median concentrations of TFF1, TFF3, NGAL, and microalbumin in patients were 44.5, 176.5, 281.2, and 15.5 mcg/gCr, respectively, and were significantly elevated as compared to controls (p < 0.05). Children belonging to group 2 had significantly higher concentration of biomarkers as compared to those in group 1. TFF3 was found have the highest AUC (0.9198) on ROC curve for predicting progressive functional deterioration.

Conclusion

Urinary TFFs, NGAL, and microalbumin significantly correlate with progressive deterioration of kidney function in children harboring CAKUT. TFF3, with the strongest prediction of functional deterioration, is an emerging peptide showing sufficient potential to be included in the biomarker panel.

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Acknowledgments

The authors are grateful to Prof. Balram Bhargava, Director General, Indian Council of Medical Research for providing support for this project

Funding

The study was funded by the Indian Council for Medical Research (ICMR).

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Authors and Affiliations

  1. Department of Pediatric Surgery, Room No 4002, Fourth Floor, Teaching Block, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India

    Sachit Anand, Minu Bajpai & Alok Kumar

  2. Division of Non-communicable Diseases, Indian Council of Medical Research, New Delhi, India

    Tripti Khanna

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  1. Sachit Anand
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  2. Minu Bajpai
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  4. Alok Kumar
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Contributions

Design of the study: Minu Bajpai. Data collection and analysis: Sachit Anand and Alok Kumar. Drafting of manuscript: Sachit Anand. Interpretation of results: Sachit Anand, Minu Bajpai, and Tripti Khanna. Revision of manuscript: Minu Bajpai and Tripti Khanna. All authors approve the final manuscript and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Minu Bajpai.

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Ethical approval

The protocol of the study was approved by the institutional review board prior to starting the study (Ref. No. IECPG-524/29.08.2019, RT-10/26.09.2019).

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Written informed consent was obtained from parents for participation.

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Anand, S., Bajpai, M., Khanna, T. et al. Urinary biomarkers as point-of-care tests for predicting progressive deterioration of kidney function in congenital anomalies of kidney and urinary tract: trefoil family factors (TFFs) as the emerging biomarkers. Pediatr Nephrol 36, 1465–1472 (2021). https://doi.org/10.1007/s00467-020-04841-8

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  • DOI: https://doi.org/10.1007/s00467-020-04841-8

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