title: Renal hyperfiltration is associated with glucose-dependent changes in fractional excretion of sodium in patients with uncomplicated type 1 diabetes.
abstract: OBJECTIVE
  Renal hyperfiltration is a common abnormality associated with diabetic nephropathy in patients with type 1 diabetes (T1D). In animal models, increased proximal tubular sodium reabsorption results in decreased distal sodium delivery, tubuloglomerular feedback activation, afferent vasodilatation, and hyperfiltration. The role of tubular factors is less well understood in humans. The aim of the current study was therefore to compare the fractional sodium excretion (FENa) in hyperfiltering (T1D-H) versus normofiltering (T1D-N) patients and healthy control (HC) subjects, as well as the role of ambient hyperglycemia on FENa.
  
  
  METHODS
  Blood pressure, renal function (inulin for glomerular filtration rate [GFR], and paraaminohippurate for effective renal plasma flow), FENa, and circulating neurohormones were measured in T1D-H (n = 28, GFR ≥135 mL/min/1.73 m(2)), T1D-N (n = 30), and HC (n = 35) subjects during clamped euglycemia. Studies were repeated in a subset of patients during clamped hyperglycemia.
  
  
  RESULTS
  During clamped euglycemia, T1D-H exhibited lower FENa than T1D-N and HC subjects (0.64 ± 0.06% vs. 0.91 ± 0.12% and 0.90 ± 0.10%, P < 0.05). During clamped hyperglycemia, FENa increased (Δ + 0.88 ± 0.22% vs. Δ + 0.02 ± 0.21%; between-group effect, P = 0.01) significantly in T1D-H, whereas FENa did not change in T1D-N. When treated as continuous variables, elevated GFR values were associated with hyperglycemia-induced increases in FENa (R(2) = 0.20, P = 0.007).
  
  
  CONCLUSIONS
  Patients with uncomplicated T1D-H exhibit lower FENa under euglycemic conditions, which may help to identify patients with hyperfiltration outside of a controlled laboratory setting. Increased FENa in T1D-H but not T1D-N under clamped hyperglycemic conditions suggests that the mechanisms responsible for increased sodium reabsorption leading to hyperfiltration can be saturated.
authors.affiliation: Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Gary K
authors.initials: GK
authors.lastname: Yang
authors.affiliation: Department of Medicine, Division of Nephrology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ronnie L H
authors.initials: RL
authors.lastname: Har
authors.affiliation: Department of Medicine, Division of Nephrology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Lytvyn
authors.affiliation: University Health Network, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Yip
authors.affiliation: Department of Medicine, Division of Nephrology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada david.cherney@uhn.ca.
authors.forename: David Z I
authors.initials: DZ
authors.lastname: Cherney
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001786:Blood Glucose / Q000502:physiology*; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology* / Q000652:urine; D003928:Diabetic Nephropathies / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D015309:Glucose Clamp Technique; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D012964:Sodium / Q000652:urine*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D012964:Sodium