Hyperfiltration and uricosuria in adolescents with type 1 diabetes
- 339 Downloads
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.
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.
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.
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.
KeywordsGlomerular filtration rate Hyperfiltration Urine uric acid Fractionated excretion of uric acid Type 1 diabetes Children
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).
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.
- 2.Orchard TJ, Secrest AM, Miller RG, Costacou T (2010) In the absence of renal disease, 20 year mortality risk in type 1 diabetes is comparable to that of the general population: a report from the Pittsburgh Epidemiology of Diabetes Complications Study. Diabetologia 53:2312–2319CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Bjornstad P, Pyle L, Nguyen N, Snell-Bergeon JK, Bishop FK, Wadwa RP, Maahs DM (2015) Achieving international society for pediatric and adolescent diabetes and american diabetes association clinical guidelines offers cardiorenal protection for youth with type 1 diabetes. Pediatr Diabetes 16:22–30CrossRefPubMedGoogle Scholar
- 19.Chiarelli F, Cipollone F, Romano F, Tumini S, Costantini F, di Ricco L, Pomilio M, Pierdomenico SD, Marini M, Cuccurullo F, Mezzetti A (2000) Increased circulating nitric oxide in young patients with type 1 diabetes and persistent microalbuminuria: relation to glomerular hyperfiltration. Diabetes 49:1258–1263CrossRefPubMedGoogle Scholar
- 22.Roncal-Jimenez C, Garcia-Trabanino R, Barregard L, Lanaspa MA, Wesseling C, Harra T, Aragόn A, Grases F, Jarquin ER, González MA, Weiss I, Glaser J, Sánchez-Lozada LG, Johnson RJ (2015) Heat stress nephropathy from exercise-induced uric acid crystalluria: a perspective on mesoamerican nephropathy. Am J Kidney Dis. doi: 10.1053/j.ajkd.2015.08.021 PubMedGoogle Scholar
- 26.Lanaspa MA, Ishimoto T, Cicerchi C, Tamura Y, Roncal-Jimenez CA, Chen W, Tanabe K, Andres-Hernando A, Orlicky DJ, Finol E, Inaba S, Li N, Rivard CJ, Kosugi T, Sanchez-Lozada LG, Petrash JM, Sautin YY, Ejaz AA, Kitagawa W, Garcia GE, Bonthron DT, Asipu A, Diggle CP, Rodriguez-Iturbe B, Nakagawa T, Johnson RJ (2014) Endogenous fructose production and fructokinase activation mediate renal injury in diabetic nephropathy. J Am Soc Nephrol 25:2526–2538CrossRefPubMedPubMedCentralGoogle Scholar
- 28.Maahs DM, Caramori L, Cherney DZ, Galecki AT, Gao C, Jalal D, Perkins BA, Pop-Busui R, Rossing P, Mauer M, Doria A, PERL Consortium (2013) Uric acid lowering to prevent kidney function loss in diabetes: the preventing early renal function loss (PERL) allopurinol study. Curr Diab Rep 13:550–559CrossRefPubMedPubMedCentralGoogle Scholar