H. Uchiyama et al., Increased urinary nitrate excretion associated with hepatic allograft rejection in experimental rat models and clinical cases, TRANSPLAN I, 13(4), 2000, pp. 260-265
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
.