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Hyperuricemia is associated with a lower glomerular filtration rate in pediatric sickle cell disease patients

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Abstract

Background

Sickle cell nephropathy (SCN) is a progressive disease that contributes significant morbidity and mortality in sickle cell disease (SCD), yet it remains poorly understood. Hyperuricemia negatively impacts renal function in the non-sickle cell population but is understudied in SCD.

Methods

We performed a cross-sectional analysis of the first 78 pediatric SCD patients enrolled in a cohort study. The mechanism of development of hyperuricemia (defined, serum uric acid (UA) ≥ 5.5 mg/dL) was characterized as a result of either UA overproduction or inefficient renal excretion by the Simkin index and fractional clearance of urate (FCU) equations. Associations between hyperuricemia and albuminuria or estimated glomerular filtration rate (eGFR) were determined by linear regression.

Results

The prevalence of hyperuricemia in this young population (mean age 11.6 ± 3.77 years) was 34.2%. Only 1 hyperuricemic participant overproduced UA by Simkin index, while 62.5% were inefficient renal excretors of UA (FCU < 4%). Hyperuricemia was associated with a significant decrease in average eGFR, −27 ml/min/1.73m2 below normouricemia (mean eGFR 151.6 ± 40.32), p = 0.0122. Notably, the previously accepted association between decline of eGFR with age is significantly modified by hyperuricemia stratification, where hyperuricemia explains 44% of the variance in eGFR by age (R2 = 0.44, p = 0.0004) and is nonsignificant in normouricemia (R2 = 0.07, p = 0.0775).

Conclusion

These findings indicate that hyperuricemia may be associated with early eGFR decline in SCN. This association must be further characterized in prospective cohort studies in SCN, and hyperuricemia must be investigated as a potential therapeutic target for SCN.

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Acknowledgments

This work was supported by the Children’s Hospital Foundation Research Scholar Award Grant to Cristin Kaspar.

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Authors and Affiliations

  1. Pediatrics, Division of Nephrology, Children’s Hospital of Richmond at Virginia Commonwealth University, 1000 E. Broad St Box 980498, Richmond, VA, 23298, USA

    Cristin D. W. Kaspar

  2. University of Vermont Larner College of Medicine, 89 Beaumont Ave, Burlington, VT, 05405, USA

    Isidora Beach

  3. Pediatrics, Division of Hematology-Oncology, Children’s Hospital of Richmond at Virginia Commonwealth University, 1000 E. Broad St Box 980498, Richmond, VA, 23298, USA

    Jennifer Newlin & India Sisler

  4. Pediatrics, Division of Nephrology, University of Alabama Birmingham, 1600 7th Avenue South, Lowder Building Suite 516, Birmingham, AL, 35233, USA

    Daniel Feig

  5. Internal Medicine, Division of Hematology, Virginia Commonwealth University, 730 E. Broad St, Richmond, VA, 23219, USA

    Wally Smith

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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Cristin Kaspar and Isidora Beach. The first draft of the manuscript was written by Cristin Kaspar, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Cristin D. W. Kaspar.

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Kaspar, C.D.W., Beach, I., Newlin, J. et al. Hyperuricemia is associated with a lower glomerular filtration rate in pediatric sickle cell disease patients. Pediatr Nephrol 35, 883–889 (2020). https://doi.org/10.1007/s00467-019-04432-2

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