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

In experimental animal studies, tumour necrosis factor-a (TNF-a) contributed to renal hypertrophy during diabetes, and antibodies against TNF-a have led to improved histological lesions in animals with nephrotoxicity and diabetic nephropathy. We aimed to evaluate TNF-a system activity in association with renal histology in patients with type 2 diabetes. This is a prospective, crosssectional study of 22 patients with type 2 diabetes (16 men), 13 with microalbuminuria and 9 with normoalbuminuria. Plasma-soluble TNF-a receptor 1 and 2 (sTNFR1 and sTNFR2) concentrations were used as surrogates of TNF-a system activity. Glomerular filtration rate (GFR) was analysed using I125-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\0.12, P[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<0.001), mesangial expansion (r = 0.59, P = 0.004) and interstitial fraction (r = 0.58, P = 0.005). After controlling for age, body mass index and blood pressure, the association of TNFR1 with mesangial expansion persisted significant. Circulating sTNFR² concentrations were not significantly associated with histological changes. In summary, structural kidney damage in patients with type 2 diabetes is associated with TNF-a system activity and specifically with plasma sTNFR1 concentrations.