Urinary protein excretion and serum tumor necrosis factor in diabetic patients with advanced renal failure: Effects of pentoxifylline administration

In 24 diabetic patients with advanced renal failure (creatinine clearance [ C-Cr] < 35 mL/min), we prospectively studied serum tumor necrosis factor-al pha (TNF-alpha) levels, the possible relationship with urinary protein excr etion, and the effects of pentoxifylline (PTF) administration. PTF (400 mg daily) was administered for 6 months to 14 patients, and the results were c ompared with data from a control group (n = 10), Baseline parameters were s imilar in both groups, At the end of the study, urinary protein excretion a nd serum TNF-a decreased in the active group from 2.7 (1.2 to 5.8) g/d and 569 +/- 285 pg/mL to 1.1 (0.3 to 4.0) g/d and 329 +/- 232 pg/mL, respective ly (P < 0.001). By contrast, proteinuria and TNF-alpha did not change in th e control group. Regression analysis showed a significant correlation betwe en proteinuria and serum TNF-alpha both at basal (r = 0.55) and at the sixt h month (r = 0.57), Furthermore, the reduction of urinary protein excretion was strongly correlated with the decrease of TNF-alpha (r = 0.72, P < 0.01 ). Serum Cr and C-Cr remained stable in both groups during the study, Our f indings suggest that cytokines might play a role in renal damage in diabeti c nephropathy, PTF is effective in reducing proteinuria in diabetic patient s with advanced renal failure. The anticytokine activity of PTF may be a fu rther explanation for this antiproteinuric effect. (C) 1999 by the National Kidney Foundation, Inc.