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Pediatric Nephrology

, Volume 31, Issue 5, pp 787–793 | Cite as

Hyperfiltration and uricosuria in adolescents with type 1 diabetes

  • Petter BjornstadEmail author
  • Carlos Roncal
  • Tamara Milagres
  • Laura Pyle
  • Miguel Angel Lanaspa
  • Franziska K. Bishop
  • Janet K. Snell-Bergeon
  • Richard J. Johnson
  • R. Paul Wadwa
  • David M. Maahs
Original Article

Abstract

Background

Urine uric acid (UUA) has been implicated in the pathogenesis of diabetic nephropathy via its effect on tubular cells. We hypothesized that the UUA level would be higher in adolescents with type 1 diabetes (T1D) than in those without T1D. We also hypothesized that UUA and fractional uric acid excretion (FeUA) would be higher in adolescents with T1D and hyperfiltration [estimated glomerular filtration rate (eGFR) ≥141 mL/min/1.73 m2] than in those without hyperfiltration.

Methods

The UUA concentration was determined and FeUA calculated in adolescents with (n = 239) and without T1D (n = 75). The eGFR was calculated using the Zappitelli equation based on serum creatinine and cystatin C concentrations.

Results

Compared to the non-diabetic adolescents enrolled in the study, those with T1D had a higher eGFR (mean ± standard deviation: 120 ± 22 vs. 112 ± 16 mL/min/1.73 m2; p = 0.0006), lower urine pH (6.2 ± 0.8 vs. 6.5 ± 1.0; p = 0.01), and higher UUA (37.7 ± 18.6 vs. 32.8 ± 18.1 mg/dL; p  = 0.049) and FeUA (median [interquartile range]: 6.2 [4.3–8.7] vs. 5.2 [3.6–7.0] %; p = 0.02). Among adolescents with T1D, those with hyperfiltration had higher median FeUA (8.6 [5.2–9.9] vs. 6.0 [4.2–8.3] %; p = 0.02) than those without hyperfiltration.

Conclusions

The adolescents with T1D enrolled in the study had higher eGFR, higher UUA and more acidic urine than the non-diabetic controls, which may have increased their risk of UUA crystallization. Adolescents with T1D and hyperfiltration had higher FeUA than those without hyperfiltration. These hypothesis-generating observations may suggest a potential pathophysiologic association between uricosuria and hyperfiltration.

Keywords

Glomerular filtration rate Hyperfiltration Urine uric acid Fractionated excretion of uric acid Type 1 diabetes Children 

Notes

Acknowledgments

Support for this study was provided by NIDDK grants (T32DK06387, DK075360), JDRF (11-2007-694), and CTSI UL-1 RR025780. The study was performed at the Barbara Davis Center for Childhood Diabetes, Aurora, CO. Dr. Maahs was supported by a grant from NIDDK (DK075360), Dr. Snell-Bergeon by an American Diabetes Association Junior Faculty Award (7-13-CD-10), and Dr. Wadwa by an early career award from the Juvenile Diabetes Research Foundation (11-2007-694).

Author contributions

PB researched, wrote, contributed to discussion, and reviewed/edited the manuscript; LP researched, performed the statistical analyses, contributed to the discussion, reviewed/edited the manuscript; CR researched, contributed to the discussion, reviewed/edited the manuscript; MGL researched, contributed to the discussion, reviewed/edited the manuscript; JKSB researched, contributed to the discussion, reviewed/edited the manuscript; RJJ researched, contributed to the discussion, reviewed/edited the manuscript; RPW researched, contributed to discussion, and reviewed/edited the manuscript; DMM researched, contributed to discussion, and reviewed/edited the manuscript.

Compliance with ethical standards

The study was approved by the Colorado Multiple Institution Review Board, and informed consent and assent (for subjects <18 years) were obtained from all subjects.

Conflict of interest disclosure

Drs. Bjornstad, Roncal, Pyle Lanaspa, Snell-Bergeon, Wadwa, and Maahs and Ms. Harra and Bishop have no conflict of interest to disclose. Dr Johnson holds a patent related to lowering uric acid in the treatment of diabetic nephropathy and has shares with XORT therapeutics.

Duality of interest

Drs. Bjornstad, Pyle and Maahs are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

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Copyright information

© IPNA 2015

Authors and Affiliations

  • Petter Bjornstad
    • 1
    • 2
    Email author
  • Carlos Roncal
    • 3
  • Tamara Milagres
    • 3
  • Laura Pyle
    • 1
  • Miguel Angel Lanaspa
    • 3
  • Franziska K. Bishop
    • 2
  • Janet K. Snell-Bergeon
    • 1
    • 2
  • Richard J. Johnson
    • 2
    • 3
  • R. Paul Wadwa
    • 1
    • 2
  • David M. Maahs
    • 1
    • 2
    • 3
  1. 1.Department of PediatricsUniversity of Colorado School of MedicineAuroraUSA
  2. 2.Barbara Davis Center for DiabetesUniversity of Colorado School of MedicineAuroraUSA
  3. 3.Department of Medicine, Division of NephrologyUniversity of Colorado School of MedicineAuroraUSA

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