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NDT Advance Access published online on August 25, 2006
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfl469
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received May 22, 2006
Accepted July 11, 2006

Original Article

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

Juan F. Navarro 1 *, Carmen Mora 2, Mercedes Muros 3, and Javier García 4

1 Nephrology Service, University Hospital, Santa Cruz de Tenerife, Spain; Research Unit, University Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain; Centre for Biological Research, Spanish National Research Council, Madrid, Spain
2 Research Unit, University Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain; Centre for Biological Research, Spanish National Research Council, Madrid, Spain
3 Research Unit, University Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain; Centre for Biological Research, Spanish National Research Council, Madrid, Spain; Clinical Biochemistry Service, Universitary Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
4 Nephrology Service, University Hospital, Santa Cruz de Tenerife, Spain

* To whom correspondence should be addressed.
Juan F. Navarro, E-mail: jnavgon{at}gobiernodecanarias.org



  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} (TNF{alpha}) 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 TNF{alpha} were measured. UAE and UNAG were determined by 24-h urine collection.

Results. Serum hs-CRP and TNF{alpha} were significantly higher in diabetic than in control subjects, as well as UAE and UNAG. Diabetic patients had increased urinary TNF{alpha} compared to non-diabetics [14.5 (2-29) vs 4 (0.8-12), P < 0.001]. Serum hs-CRP and TNF{alpha} in diabetics with increased UAE were elevated compared to diabetics having normoalbuminuria. Urinary TNF{alpha} 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 TNF{alpha} (P < 0.0001), hs-CRP (P < 0.0001), serum TNF{alpha} (P < 0.01) and HbA1c (P < 0.05) were independent of and significantly associated with UAE, whereas duration of diabetes (P < 0.001), urinary TNF{alpha} (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 TNF{alpha} excretion is elevated and correlates with severity of renal disease in terms of both glomerular and tubulointerstitial damage, suggesting a significant role for TNF{alpha} in the pathogenesis and progression of renal injury in diabetes mellitus.

Keywords: albuminuria; cytokines; diabetes mellitus; diabetic nephropathy; tumour necrosis factor-{alpha}.
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