TRANSFORMING GROWTH-FACTOR BETA(1) IN RENAL-ALLOGRAFT RECIPIENTS

Transforming growth factor beta (TGF beta(1)) is a prosclerotic cytokine implicated in several disease processes. Recent reports have demonstrated a role for TGF beta(1) in experimental models of glomerulonephritis, focusing attention on the relevance of TGF beta to renal fibrogenesis in human disease. The study reported here was designed to investigate whether circulating, active TG:FP, could be detected in renal allograft recipients, and whether plasma levels correlated with episodes of rejection, a process involving both inflammation and fibrosis. We have developed an ELISA assay for active TGF beta(1) using commercially available antibodies, and measured plasma levels in 43 healthy controls, 11 patients with membranous nephropathy (MN) and impaired renal function, 17 transplant recipients with stable renal function, 27 patients with acute cellular rejection, 7 patients with chronic vascular rejection, and 10 patients with acute tubular necrosis and/or cyclosporine toxicity. In the last three groups diagnoses were biopsy-proved, and all samples were collected at the time of biopsy. TGF beta(1) was also measured in urine samples from 8, 11, 0, 9, 4, and 7 individuals, respectively, from each group. TGF beta(1) was not detected in plasma from any of the healthy controls or any of the MN patients, (detection limit of assay 0.1 ng/ml). By comparison, it was significantly increased in all groups of transplant recipients (unpaired t test, P<0.01), but there were no significant differences between the transplant groups. Plasma TGF beta(1) level did not correlate with renal function (estimated by either serum creatinine or reciprocal creatinine), kidney donor age, recipient age, time since transplantation, or cyclosporine plasma trough level. TGF beta(1) was found in every urine sample tested from healthy controls, with a range from 1 ng/ml to 35 ng/ml. Among the 20 transplant patient urines tested, 2 were negative, 18 were positive but within the range determined for the healthy controls. There were no significant differences between the groups.