title: The effect of renal hyperfiltration on urinary inflammatory cytokines/chemokines in patients with uncomplicated type 1 diabetes mellitus.
abstract: OBJECTIVE
  High intraglomerular pressure causes renal inflammation in experimental models of diabetes. Our objective was to determine whether renal hyperfiltration, a surrogate for intraglomerular hypertension, is associated with increased excretion of urinary cytokines/chemokines in patients with type 1 diabetes mellitus.
  
  
  METHODS
  Blood pressure, renal haemodynamic function (inulin and para-aminohippurate clearances for glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), respectively) and urine samples were obtained during clamped euglycaemia in individuals with type 1 diabetes with either hyperfiltration (GFR determined using inulin [GFRINULIN] ≥ 135 ml min⁻¹ 1.73 m⁻², n = 28) or normofiltration (n = 21) and healthy control individuals (n = 18).
  
  
  RESULTS
  Baseline clinical characteristics, dietary sodium and protein intake and blood pressure levels were similar in the diabetic and healthy control groups. In addition, HbA1c levels were similar in the two diabetic groups. As expected baseline GFR was higher in hyperfilterers than either normofiltering diabetic patients or healthy control patients (165 ± 9 vs 113 ± 2 and 116 ± 4 ml min⁻¹ 1.73 m⁻², respectively, p < 0.01). ERPF and renal blood flow were also comparatively higher and renal vascular resistance was lower in hyperfiltering patients (p < 0.01). Hyperfiltering diabetic patients had higher excretion rates for eotaxin, IFNα2, macrophage-derived chemokine, platelet-derived growth factor (PDGF)-AA, PDGF-AB/BB and granulocyte-macrophage colony-stimulating factor (p ≤ 0.01). Urinary monocyte chemoattractant protein (MCP)-1 and RANTES (regulated on activation, normal T expressed and secreted) excretion was also higher in hyperfiltering vs normofiltering diabetic individuals (p < 0.01) and fibroblast growth factor-2, MCP-3 and CD40K excretion was elevated in hyperfiltering diabetic individuals vs healthy controls (p < 0.01).
  
  
  CONCLUSIONS
  Renal hyperfiltration is associated with increased urinary excretion of inflammatory cytokines/chemokines in patients with uncomplicated type 1 diabetes.
authors: Division of Nephrology, Toronto General Hospital, University Health Network, Banting and Best Diabetes Centre, University of Toronto, 585 University Ave, 8N-845, Toronto, ON, Canada M5G 2N2.
authors: R
authors: R
authors: Har
authors: J W
authors: JW
authors: Scholey
authors: D
authors: D
authors: Daneman
authors: F H
authors: FH
authors: Mahmud
authors: R
authors: R
authors: Dekker
authors: V
authors: V
authors: Lai
authors: Y
authors: Y
authors: Elia
authors: M L
authors: ML
authors: Fritzler
authors: E B
authors: EB
authors: Sochett
authors: H N
authors: HN
authors: Reich
authors: D Z I
authors: DZ
authors: Cherney
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000652:urine; D018925:Chemokines / Q000652:urine*; D015331:Cohort Studies; D016207:Cytokines / Q000652:urine*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000175:diagnosis / Q000276:immunology / Q000503:physiopathology* / Q000652:urine; D042241:Early Diagnosis; D005260:Female; D060730:Glomerular Filtration Barrier / Q000276:immunology / Q000503:physiopathology*; D005919:Glomerular Filtration Rate; D015309:Glucose Clamp Technique; D006801:Humans; D008297:Male; D010865:Pilot Projects; D012079:Renal Circulation; D012720:Severity of Illness Index; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines