Uromodulin levels are decreased in urine during acute tubular necrosis but not during immune rejection after renal transplantation.

1. Uromodulin, an immunosuppressive glycoprotein found in urine, is a high-affinity binding ligand for certain cytokines, including tumour necrosis factor. 2. Its occurrence in urine was monitored after renal transplantation to investigate whether this simple urine test might differentiate common early causes of graft failure: acute immune rejection and acute tubular necrosis. 3. Diluted urine was assayed for uromodulin using a sandwich enzyme-linked immunosorbent assay. When graft function failed due to acute tubular necrosis, urinary uromodulin levels were significantly depressed compared with levels in urine produced during biopsy-proven acute immune rejection episodes (P < 0.01) or during periods of stable graft function (P < 0.02). This suggests that urinary levels of uromodulin may reflect tubular damage rather than other causes of graft functional failure. 4. The cytokine tumour necrosis factor, which binds with high affinity to uromodulin, was found in 30% of urine samples in association with immune rejection episodes, but not during acute tubular necrosis. However, the presence of urinary tumour necrosis factor was not related to levels of uromodulin in the same sample.