Nitric oxide production and nitric oxide synthase expression in acute human renal allograft rejection

Background Nitric oxide (NO) is produced by nitric oxide synthases (NOS), w hich are either constitutively expressed in the kidney or inducible, in res ident and infiltrating cells during inflammation and allograft rejection. N O is rapidly degraded to the stable end products nitrite and nitrate, which can be measured in serum and urine, and may serve as noninvasive markers o f kidney allograft rejection. Methods. Total nitrite and nitrate levels (NOx) were measured in serum and urine thrice meekly after an overnight fast in 18 consecutive patients foll owing renal cadaveric transplantation. Inducible NOS (iNOS) and endothelial NOS (eNOS) expression was immunochemically determined in renal biopsy spec imens with or without acute rejection (AR). Results. Serum NOx levels increased days before AR and were significantly h igher at the moment of AR (27 +/- 12.4 mu mol/L) compared with recipients w ith an uncomplicated course (13 +/- 7.6 mu mol/L), but not compared with re cipients with cyclosporine (CsA) toxicity (20 +/- 13.0 mu mol/L), Urinary N Ox levels were significantly lower during AR (20 +/- 13.6 mu mol/mmol creat inine) compared with an uncomplicated course (64 +/- 25.2 mu mol/mmol creat inine) or CsA toxicity (53.8 +/- 28.3 mu mol/mmol creatinine). Interstitial and glomerular iNOS expression was significantly increased in biopsy speci mens showing AR. Unexpectedly glomerular eNOS expression was significantly decreased in patients with AR. Conclusions. This study reports differences in NOx levels in serum and urin e, which may help discriminate AR episodes from an uncomplicated course or CsA toxicity. As expected, renal iNOS expression is increased in acute allo graft rejection, The decrease in glomerular eNOS expression suggests an int riguing link between acute and chronic rejection.