DECREASED URINARY-EXCRETION OF NITRIC-OXIDE IN ACUTE - REJECTION EPISODES IN PEDIATRIC RENAL-ALLOGRAFT RECIPIENTS

Acute renal allograft rejection continues to have a negative effect on graft survival despite a better understanding of the molecular basis of renal allograft rejection. Nitric oxide (NO) has important biologic al functions in cell defense and injury and some evidence exists that it may act as an immunomodulator in allograft transplantation. To dete rmine if NO has any role in acute renal allograft rejection in pediatr ic patients, acute rejection episodes in pediatric renal transplant re cipients were evaluated. Four out of eleven patients who received a re nal allograft in 1995 at Children's Kidney Center at The Children's Ho spital of Buffalo had eight episodes of acute rejection. One patient r eceived a living-related and three received cadaveric grafts. Stable m etabolites of NO (NO-2 + NO-3 = NOx) were measured in the serum and ur ine samples of the patients daily. Serum levels of NO did not change s ignificantly during acute rejection episodes. Urinary NO, levels decre ased by 73+/-9% of the baseline values during episodes of acute reject ion: mean +/- SE urinary nitric oxide/creatinine ratio (NOx/Cr) of 0.1 7+/-0.05 at baseline vs. 0.05+/-0.01 during rejection (P=0.02). Succes sful treatment of acute rejection by administration of high dose i.v. steroids or OKT-3 induced acute rises in the urinary NO levels to base line values: NO/Cr = 0.17+/-0.04 (mean +/- SE). We conclude that urina ry NO excretion decreases significantly during acute renal allograft r ejection and that NOx concentration in the urine increases in response to successful antirejection therapy.