PLASMA-LEVELS OF TUMOR-NECROSIS-FACTOR (TNF) AND SOLUBLE TNF RECEPTORS IN KIDNEY-TRANSPLANT RECIPIENTS

Tumor necrosis factor-alpha is elevated in plasma during kidney transp lant rejection. However, the measurement and biological activity of TN F alpha is influenced by inhibitory soluble TNF receptors. We therefor e determined plasma levels of TNF alpha and the 2 soluble TNF receptor s, the 55-kDa TNF receptor (TNF-sR55) and the 75-kDa TNF receptor (TNF -sR75), by immunoassays in 25 patients before and daily after kidney t ransplantation. Plasma samples were retrospectively assigned to 3 grou ps: (1) patients with well-functioning grafts (n=14); (2) patients wit h biopsy-proven graft rejections (n=7 patients with 10 rejections); an d (3) patients with episodes of CsA nephrotoxicity (n=4 patients with 9 samples). On the day of biopsy-proven graft rejection, TNF(li increa sed from 8.6+/-0.9 pg/ml to 14.8+/-3.5 pg/ml (P<0.02), TNF-sR55 from 6 .6+/-1.3 ng/ml to 9.0+/-1.2 ng/ml (NS), and TNF-sR75 from 10.3+/-1.0 n g/ml to 15.3+/-2.0 ng/ml (P<0.01). During episodes of CsA toxicity, TN F alpha levels did not change, TNF-sR55 increased from 5.2+/-0.5 ng/ml to 10.5+/-0.5 ng/ml (P<0.01), and TNF-sR75 increased from 10.2+/-0.8 ng/ml to 17.5+/-0.9 ng/ml (P<0.01). There was a strong correlation bet ween serum creatinine and plasma TNF-sR55 (r=0.7, P<0.001) and TNF-sR7 5 (r=0.7, P<0.001), but not with TNF alpha. Therefore, levels of TNF-s R55 and TNF-sR75 were corrected for serum creatinine. An index express ing TNF alpha over actively released soluble receptors (index = TNF al pha/(corr.TNF-sR55 + corr.TNF-sR75)) detected rejection episodes with a sensitivity of 70-80% and a specificity of 89%. We conclude that the measurement of plasma TNF alpha in combination with its soluble recep tors is superior to isolated TNF alpha determinations in discriminatin g acute graft rejection from episodes of CsA toxicity in kidney transp lant recipients.