Urinary tumour necrosis factor-alpha excretion independently correlates with clinical markers of glomerular and tubulointerstitial injury in type 2 diabetic patients

Nephrol Dial Transplant. 2006 Dec;21(12):3428-34. doi: 10.1093/ndt/gfl469. Epub 2006 Aug 25.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / urine
  • Cytokines / urine*
  • Diabetes Mellitus, Type 2 / urine*
  • Diabetic Nephropathies / urine*
  • Female
  • Humans
  • Kidney Glomerulus / metabolism
  • Kidney Tubules / metabolism
  • Male
  • Middle Aged
  • Tumor Necrosis Factor-alpha / urine*


  • Biomarkers
  • Cytokines
  • Tumor Necrosis Factor-alpha