title: Urinary tumour necrosis factor-alpha excretion independently correlates with clinical markers of glomerular and tubulointerstitial injury in type 2 diabetic patients.
abstract: BACKGROUND
  Inflammation is a potential factor in the development and progression of diabetic nephropathy. The aim of this study was to analyse the relationship between the pro-inflammatory cytokine tumour necrosis factor-alpha (TNFalpha) and clinical markers of glomerular and tubulointerstitial damage [urinary albumin excretion (UAE) and urinary N-acetyl-beta-glucosaminidase (UNAG), respectively] in a large group of type 2 diabetic patients.
  
  
  METHODS
  A total of 160 diabetic patients and 32 healthy controls were included in the study. High-sensitive C-reactive protein (hs-CRP) as well as serum and urinary levels of TNFalpha were measured. UAE and UNAG were determined by 24-h urine collection.
  
  
  RESULTS
  Serum hs-CRP and TNFalpha were significantly higher in diabetic than in control subjects, as well as UAE and UNAG. Diabetic patients had increased urinary TNFalpha compared to non-diabetics [14.5 (2-29) vs 4 (0.8-12), P < 0.001]. Serum hs-CRP and TNFalpha in diabetics with increased UAE were elevated compared to diabetics having normoalbuminuria. Urinary TNFalpha was also higher in diabetic subjects with micro- or macroalbuminuria than in patients with normal UAE [10.5 (4-20) and 18 (9-29) vs 7 (2-18) pg/mg, P < 0.0001, respectively]. Multiple regression analysis showed that urinary TNFalpha (P < 0.0001), hs-CRP (P < 0.0001), serum TNFalpha (P < 0.01) and HbA1c (P < 0.05) were independent of and significantly associated with UAE, whereas duration of diabetes (P < 0.001), urinary TNFalpha (P < 0.01), HbA1c (P = 0.01), hs-CRP (P < 0.05) and serum creatinine (P < 0.05) were associated with UNAG.
  
  
  CONCLUSIONS
  In patients with type 2 diabetes, urinary TNFalpha excretion is elevated and correlates with severity of renal disease in terms of both glomerular and tubulointerstitial damage, suggesting a significant role for TNFalpha in the pathogenesis and progression of renal injury in diabetes mellitus.
authors.affiliation: Nephrology Service, Hospital Nuestra Señora de Candelaria, Carretera del Rosario, 145, 38010 Santa Cruz de Tenerife, Tenerife, Spain. jnavgon@gobiernodecanarias.org
authors.forename: Juan F
authors.initials: JF
authors.lastname: Navarro
authors.forename: Carmen
authors.initials: C
authors.lastname: Mora
authors.forename: Mercedes
authors.initials: M
authors.lastname: Muros
authors.forename: Javier
authors.initials: J
authors.lastname: García
mesh_terms: D015415:Biomarkers / Q000652:urine; D016207:Cytokines / Q000652:urine*; D003924:Diabetes Mellitus, Type 2 / Q000652:urine*; D003928:Diabetic Nephropathies / Q000652:urine*; D005260:Female; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000652:urine*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha