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Association of clinical characteristics with urine uromodulin in children with chronic kidney disease

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Abstract  

Background

Uromodulin is the most abundant protein in the urine of healthy adults, and higher urine concentrations mark better tubular health. Greater kidney size and function are predictors of higher uromodulin levels in adults. Urine uromodulin has not yet been studied in children with chronic kidney disease (CKD). Thus, we sought to determine the relationship between age and kidney function with urine uromodulin levels in children with CKD.

Methods

In the CKD in Children (CKiD) cohort, we utilized multivariable linear regression to evaluate the relationship of age and eGFR with urine uromodulin levels. The primary outcome was uromodulin indexed to urine creatinine (Umod/Cr, mg/g), which was log2-transformed given its skewed distribution.

Results

Among 677 CKiD participants, the median age was 11.8 years (8.2–15.3), the median eGFR was 49 ml/min/1.73 m2 (37–63), the etiology of CKD was glomerular disease in 31%, and the median Umod/Cr level was 0.114 mg/g (0.045–0.226). In the multivariable models, each one-year older age was associated with 0.18 (12%) lower log2(Umod/Cr) and 0.20 (13%) lower log2(Umod/Cr) among those with non-glomerular and glomerular disease, respectively (p < 0.001). However, we did not find a statistically significant association between eGFR and Umod/Cr in either participants with non-glomerular or glomerular disease (p = 0.13 and p = 0.58, respectively).

Conclusions

Among children with CKD, older age is significantly associated with lower Umod/Cr, independent of eGFR. Further studies are needed to comprehensively evaluate age-specific reference ranges for urine uromodulin and to evaluate the longitudinal relationship of uromodulin with both age and eGFR in children with CKD.

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Data availability

The CKiD cohort de-identified participant data and data dictionaries used in our analyses are available through the NIDDK Central Repository upon reasonable request.

Change history

  • 29 April 2023

    The links to the Graphical Abstract and Supplementary Information have been corrected.

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Acknowledgements

Data in this manuscript were collected by the Chronic Kidney Disease in children prospective cohort study (CKiD) 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. The CKiD website is located at https://statepi.jhsph.edu/ckid and a list of CKiD collaborators can be found at https://statepi.jhsph.edu/ckid/site-investigators/.

Funding

The CKiD study is supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and 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, and U24DK066116). The work for this ancillary study was supported by the NIDDK through grant K23 DK129836 (CYB). This work was also supported by American Heart Association Grant # 857722 (CYB).

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Authors and Affiliations

  1. Clinical and Translational Research Accelerator, Yale University, New Haven, CT, USA

    Sophia C. Faulkner, Jason H. Greenberg & Christine Y. Bakhoum

  2. Bloomberg School of Public Health, John Hopkins University, Baltimore, MD, USA

    Matthew B. Matheson

  3. Department of Pediatrics, Section of Pediatric Nephrology, Yale University, New Haven, CT, USA

    Jason H. Greenberg & Christine Y. Bakhoum

  4. Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, La Jolla, CA, USA

    Pranav S. Garimella & Joachim H. Ix

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

    Susan L. Furth

  6. Nephrology Section, Medicine Service, Veterans Affairs San Diego Healthcare System, La Jolla, CA, USA

    Joachim H. Ix

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  1. Sophia C. Faulkner
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  2. Matthew B. Matheson
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  3. Jason H. Greenberg
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  4. Pranav S. Garimella
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  7. Christine Y. Bakhoum
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Correspondence to Christine Y. Bakhoum.

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Faulkner, S.C., Matheson, M.B., Greenberg, J.H. et al. Association of clinical characteristics with urine uromodulin in children with chronic kidney disease. Pediatr Nephrol 38, 3859–3862 (2023). https://doi.org/10.1007/s00467-023-05947-5

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  • DOI: https://doi.org/10.1007/s00467-023-05947-5

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