Hyperfiltration and uricosuria in adolescents with type 1 diabetes

Pediatr Nephrol. 2016 May;31(5):787-93. doi: 10.1007/s00467-015-3299-8. Epub 2015 Dec 23.

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 m(2)] 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 m(2); 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: Children; Fractionated excretion of uric acid; Glomerular filtration rate; Hyperfiltration; Type 1 diabetes; Urine uric acid.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Factors
  • Biomarkers / blood
  • Biomarkers / urine
  • Case-Control Studies
  • Child
  • Creatinine / blood
  • Cross-Sectional Studies
  • Cystatin C / blood
  • Diabetes Mellitus, Type 1 / complications*
  • Diabetes Mellitus, Type 1 / diagnosis
  • Diabetic Nephropathies / diagnosis
  • Diabetic Nephropathies / etiology*
  • Diabetic Nephropathies / physiopathology
  • Diabetic Nephropathies / urine
  • Female
  • Glomerular Filtration Rate*
  • Humans
  • Hydrogen-Ion Concentration
  • Kidney / physiopathology*
  • Male
  • Models, Biological
  • Predictive Value of Tests
  • Up-Regulation
  • Uric Acid / urine*
  • Young Adult

Substances

  • Biomarkers
  • CST3 protein, human
  • Cystatin C
  • Uric Acid
  • Creatinine