Structural damage in diabetic nephropathy is associated with TNF-α system activity

In experimental animal studies, tumour necrosis factor-α (TNF-α) contributed to renal hypertrophy during diabetes, and antibodies against TNF-α have led to improved histological lesions in animals with nephrotoxicity and diabetic nephropathy. We aimed to evaluate TNF-α system activity in association with renal histology in patients with type 2 diabetes. This is a prospective, cross-sectional study of 22 patients with type 2 diabetes (16 men), 13 with microalbuminuria and 9 with normoalbuminuria. Plasma-soluble TNF-α receptor 1 and 2 (sTNFR1 and sTNFR2) concentrations were used as surrogates of TNF-α system activity. Glomerular filtration rate (GFR) was analysed using I 125 -Iodothalamine. Albumin excretion rate (AER) and a renal biopsy were performed in all subjects. AER did not associate significantly with mesangial expansion or interstitial fraction in these subjects ( r 0.5). AER was also not associated with either sTNFR1 or sTNFR2 levels. However, after controlling for GFR, the correlation between AER and sTNFR1 became significant ( r = 0.47, P = 0.03). sTNFR1 correlated with age ( r = 0.65, P