NDT Advance Access originally published online on August 25, 2006
Nephrology Dialysis Transplantation 2006 21(12):3428-3434; doi:10.1093/ndt/gfl469
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Urinary tumour necrosis factor-
excretion independently correlates with clinical markers of glomerular and tubulointerstitial injury in type 2 diabetic patients
1Nephrology Service, University Hospital, Santa Cruz de Tenerife, Spain 2Research Unit, University Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain, 3Centre for Biological Research, Spanish National Research Council, Madrid and 4Clinical Biochemistry Service, Universitary Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
Correspondence and offprint requests to: Juan F. Navarro, MD, FASN, Nephrology Service, Hospital Nuestra Señora de Candelaria, Carretera del Rosario, 145, 38010 Santa Cruz de Tenerife, Tenerife, Spain. Email: jnavgon{at}gobiernodecanarias.org
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-
(TNF) and clinical markers of glomerular and tubulointerstitial damage [urinary albumin excretion (UAE) and urinary N-acetyl-ß-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 were measured. UAE and UNAG were determined by 24-h urine collection.
Results. Serum hs-CRP and TNF were significantly higher in diabetic than in control subjects, as well as UAE and UNAG. Diabetic patients had increased urinary TNF compared to non-diabetics [14.5 (2–29) vs 4 (0.8–12), P < 0.001]. Serum hs-CRP and TNF in diabetics with increased UAE were elevated compared to diabetics having normoalbuminuria. Urinary TNF 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 (P < 0.0001), hs-CRP (P < 0.0001), serum TNF (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 (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 excretion is elevated and correlates with severity of renal disease in terms of both glomerular and tubulointerstitial damage, suggesting a significant role for TNF in the pathogenesis and progression of renal injury in diabetes mellitus.
Keywords: albuminuria; cytokines; diabetes mellitus; diabetic nephropathy; tumour necrosis factor-
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