The TNF-alpha system after successful living-related kidney transplantation.

Abstract

The TNF-alpha system is thought to play a central role in the reduced immunity of haemodialysis patients. The imbalance between the high levels of soluble TNF receptors R1 and R2 and the low levels of immunoactive TNF-alpha results in an increased TNF-alpha buffering capacity leading to reduced immune responses. Apart from impaired renal clearance of the receptors, inefficient TNF-alpha production as a result of the uraemia may also contribute to the imbalance between this cytokine and its receptors. In patients receiving a living-related kidney transplant, renal function is nearly normalized in a very short period. This restoration of renal function may result in a state of better immunocompetence, either as a result of improved clearance of the receptors or as a result of reversal of the uraemic state. To differentiate between these two possibilities, we measured TNF-alpha protein, mRNA and the soluble TNF receptors R1 and R2 before and after successful renal transplantation. TNF-alpha mRNA was not affected by transplantation, indicating constant TNF-alpha production. The imbalance in the TNF-alpha system was markedly improved after transplantation, although normal values of the soluble receptors were not reached. One year after transplantation in stable kidney transplant recipients there was still an imbalance in the TNF-alpha system caused by persistently elevated levels of the soluble TNF-receptors. These results suggest that even after successful kidney transplantation the TNF-alpha system remains activated. However, despite immunosuppressive therapy, recipients of a living-related kidney do have a better balanced TNF-alpha system compared to haemodialysis patients.