title: Hyperfiltration and uricosuria in adolescents with type 1 diabetes.
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.
authors.affiliation: Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA. Petter.Bjornstad@childrenscolorado.org.|Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO, USA. Petter.Bjornstad@childrenscolorado.org.
authors.forename: Petter
authors.initials: P
authors.lastname: Bjornstad
authors.affiliation: Department of Medicine, Division of Nephrology, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Roncal
authors.affiliation: Department of Medicine, Division of Nephrology, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: Tamara
authors.initials: T
authors.lastname: Milagres
authors.affiliation: Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Pyle
authors.affiliation: Department of Medicine, Division of Nephrology, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Lanaspa
authors.affiliation: Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: Franziska K
authors.initials: FK
authors.lastname: Bishop
authors.affiliation: Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.|Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: Janet K
authors.initials: JK
authors.lastname: Snell-Bergeon
authors.affiliation: Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO, USA.|Department of Medicine, Division of Nephrology, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Johnson
authors.affiliation: Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.|Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: R Paul
authors.initials: RP
authors.lastname: Wadwa
authors.affiliation: Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.|Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO, USA.|Department of Medicine, Division of Nephrology, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Maahs
mesh_terms: D000293:Adolescent; D000367:Age Factors; D015415:Biomarkers / Q000097:blood / Q000652:urine; D016022:Case-Control Studies; D002648:Child; D003404:Creatinine / Q000097:blood; D003430:Cross-Sectional Studies; D055316:Cystatin C / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000175:diagnosis; D003928:Diabetic Nephropathies / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D008954:Models, Biological; D011237:Predictive Value of Tests; D015854:Up-Regulation; D014527:Uric Acid / Q000652:urine*; D055815:Young Adult
chemical_list: D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D014527:Uric Acid; D003404:Creatinine
keywords: Children; Fractionated excretion of uric acid; Glomerular filtration rate; Hyperfiltration; Type 1 diabetes; Urine uric acid