Decreased Urinary Excretion of Nitric Oxide in Acute Rejection Episodes in Pediatric Renal Allograft Recipients1

Abstract

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 biological functions in cell defense and injury and some evidence exists that it may act as an immunomodulator in allograft transplantation. To determine if NO has any role in acute renal allograft rejection in pediatric patients, acute rejection episodes in pediatric renal transplant recipients were evaluated. Four out of eleven patients who received a renal allograft in 1995 at Children's Kidney Center at The Children's Hospital of Buffalo had eight episodes of acute rejection. One patient received a living-related and three received cadaveric grafts. Stable metabolites of NO (NO-2 + NO-3 = NOx) were measured in the serum and urine samples of the patients daily. Serum levels of NO did not change significantly during acute rejection episodes. Urinary NOx levels decreased by 73+/-9% of the baseline values during episodes of acute rejection: mean +/-SE urinary nitric oxide/creatinine ratio (NOx/Cr) of 0.17+/-0.05 at baseline vs. 0.05+/-0.01 during rejection (P=0.02). Successful treatment of acute rejection by administration of high dose i.v. steroids or OKT-3 induced acute rises in the urinary NO levels to baseline values: NO/Cr = 0.17+/-0.04 (mean +/-SE). We conclude that urinary NO excretion decreases significantly during acute renal allograft rejection and that NOx concentration in the urine increases in response to successful antirejection therapy.

Expression of Inducible and Endothelial Nitric Oxide Synthases, Formation of Peroxynitrite and Reactive Oxygen Species in Human Chronic Renal Transplant Failure

“…In humans, conflicting data on NO x levels in both serum and urine have been found in acute renal allograft rejection (15)(16)(17)(18). Using immunohistochemistry, we recently found an increase in interstitial and glomerular iNOS expression and a decrease in glomerular eNOS expression in patients with AR compared with control kidneys (17).…”

Influence of Endothelial Nitric Oxide Synthase Gene Polymorphisms (-786T/C, 4a4b, 894G/T) on Iranian Kidney Transplant Recipients

“…3,4 There are reports about the role of NO in I/R and allograft rejection in liver, heart, kidney, and pancreatic islet cell transplant. [21][22][23][24][25][26][27] Inhaled NO or NO donor drugs are novel treatments that have been used clinically to diminish I/R.…”

Metabonomics Study of Intestinal Transplantation Using Ultrahigh-Performance Liquid Chromatography Time-of-Flight Mass Spectrometry

“…Recently, most metabolomic studies were focused on kidney transplantation to assess biomarkers associated with posttransplantation function, renal dysfunction, acute rejection and subclinical rejection [1,9,10,11,12,13,14,15,16,17] and others on liver and heart transplantation [18,19,20,21] to identify prognostic and diagnostic markers of organ rejection and dysfunction [22,23,24]. This is the first time that the metabonomics technique has been applied to human intestinal transplantation.…”