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Longitudinal kidney injury biomarker trajectories in children with obstructive uropathy

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Abstract

Background

Congenital obstructive uropathy (OU) is a leading cause of pediatric kidney failure, representing a unique mechanism of injury, in part from renal tubular stretch and ischemia. Tubular injury biomarkers have potential to improve OU-specific risk stratification.

Methods

Patients with OU were identified in the Chronic Kidney Disease in Children (CKiD) study. “Cases” were defined as individuals receiving any kidney replacement therapy (KRT), while “controls” were age- and time-on-study matched and KRT free at last study visit. Urine and plasma neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), and liver-type fatty acid-binding protein (L-FABP) levels were measured at enrollment and annually and compared between cases and controls. Urine values were normalized to urine creatinine.

Results

In total, 22 cases and 22 controls were identified, with median (interquartile range) ages of 10.5 (9.0–13.0) and 15.9 (13.9–16.9) years at baseline and outcome, respectively. At enrollment there were no differences noted between cases and controls for any urine (u) or plasma (p) biomarker measured. However, the mean pNGAL and uL-FABP/creatinine increased throughout the study period in cases (15.38 ng/ml per year and 0.20 ng/ml per mg/dl per year, respectively, p = 0.01 for both) but remained stable in controls. This remained constant after controlling for baseline glomerular filtration rate (GFR).

Conclusions

In children with OU, pNGAL and uL-FABP levels increased over the 5 years preceding KRT; independent of baseline GFR. Future studies are necessary to identify optimal cutoff values and to determine if these markers outperform current clinical predictors.

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Acknowledgment

Data in this manuscript were collected by the Chronic Kidney Disease in Children (CKiD) prospective cohort study with clinical coordinating centers (principal investigators) at Children’s Mercy Hospital and the University of Missouri, Kansas City (Bradley Warady, MD), and Children’s Hospital of Philadelphia (Susan Furth, MD, PhD), Central Biochemistry Laboratory (George Schwartz, MD) at the University of Rochester Medical Center, and data coordinating center (Alvaro Muñoz, PhD and Derek Ng, PhD) at the Johns Hopkins Bloomberg School of Public Health.

Funding

The CKiD study is supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases, with additional funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Heart, Lung, and Blood Institute (U01DK66143, U01DK66174, U24DK082194, U24DK066116). The CKiD website is located at https://statepi.jhsph.edu/ckid/.

Author information

Authors and Affiliations

  1. Section of Urology, Nationwide Children’s Hospital, Columbus, OH, 43205, USA

    Daryl J. McLeod & Christina B. Ching

  2. Center for Surgical Outcomes Research, Nationwide Children’s Hospital, Columbus, OH, 43205, USA

    Daryl J. McLeod & Yuri V. Sebastião

  3. Center for Clinical and Translational Research, Nationwide Children’s Hospital, Columbus, OH, 43205, USA

    Christina B. Ching & Brian Becknell

  4. Department of Pediatrics, Section of Nephrology, Yale University School of Medicine, New Haven, CT, 06510, USA

    Jason H. Greenberg

  5. Department of Pediatrics, Division of Nephrology, Perelman School of Medicine at the University of Pennsylvania and the Children’s Hospital of Philadelphia, Philadelphia, PA, 19104, USA

    Susan L. Furth

  6. Department of Pediatrics, Section of Nephrology, Nationwide Children’s Hospital, Columbus, OH, 43205, USA

    Brian Becknell

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  1. Daryl J. McLeod
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Correspondence to Daryl J. McLeod.

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McLeod, D.J., Sebastião, Y.V., Ching, C.B. et al. Longitudinal kidney injury biomarker trajectories in children with obstructive uropathy. Pediatr Nephrol 35, 1907–1914 (2020). https://doi.org/10.1007/s00467-020-04602-7

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  • DOI: https://doi.org/10.1007/s00467-020-04602-7

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