Natural serum TNF antagonists in end-stage renal failure and following renal transplantation

TNF is clearly involved in allograft rejection but measurement of serum cytokine levels do not reflect reliably the rejection crisis. TNF induces release of soluble receptor parts that are more stable, are catabolized by kidneys and have inhibitory activity. Thus it is crucial to analyse their kinetics during renal function recovery after transplantation to forecast their potential clinical use in rejection monitoring or treatment. A sequential study was performed in 61 patients undergoing kidney graft, compared to 60 graft patients with long follow-up and 15 healthy controls. Soluble TNF and Il2 receptors were measured by ELISA and TNF was measured by RIA. The sTNF-Rs were markedly increased in renal failure, much more than another soluble cytokine receptor, the sIl2-R. Levels progressively decreased with the recovery of renal function and became directly correlated to the renal function. Normal levels were only reached after some weeks. No significant changes were observed during graft rejection at that stage of renal function but p75 were higher after antilympocyte antiserum and tubular necrosis. High sTNF-R did not seem to minimize rejection risk or gravity. In long-standing recipients, sTNF-R rose in some patients, particularly with glomerulonephritis, and may help in monitoring chronic rejection activity. sTNF-R but not sIl2-R markedly accumulate in ESRF and mask any changes that could be helpful in the monitoring of early graft events. However, increased levels above renal impairment (sTNF-R/SCr) may be clinically relevant in late rejection or glomerulonephritides.