Increased urinary nitrate excretion associated with hepatic allograft rejection in experimental rat models and clinical cases

In this study, we investigated the relationship between excretion of urinar y nitrate as a stable end-product of nitric oxide (NO) metabolism and hepat ic allograft rejection. In experimental rat models, hepatic allograft rejec tion was associated with increased nitrate excretion with a peak on postspe rative day 5. The severity of the hepatic allograft rejection was dependent on the increased urinary nitrate excretion. No significant increase in uri nary nitrate excretion was observed in cases in which effective immunosuppr ession was achieved. Inducible nitric oxide synthase mRNA expression was up regulated parallel to interferon-gamma gene expression in the graft-infiltr ating mononuclear cells and spleen cells from the recipients. In clinical c ases, urinary nitrate excretion increased parallel to increased serum cytos olic enzymes that accompanied rejection. These results suggest that urinary nitrate excretion is a useful indicator for the surveillance of graft reje ction and the monitoring of therapeutic effects of antirejection treatments .