Increased nitric oxide production during acute rejection in kidney transplantation: A useful marker to aid in the diagnosis of rejection

Background. The diagnosis of acute rejection (AR) relies on biopsy (Bx), with all the noninvasive tests failing to show satisfactory predictive value. Nitric oxide (NO) has been shown to play a role in AR. The aim of this study is to analyze the relationship between NO and (1) biopsy-proven allograft rejection and (2) other reasons of allograft dysfunction. Patients and Methods. Fifty consecutive renal allograft recipients ages 23-72 yrs who were transplanted were prospectively recruited. Blood samples were collected for 3 months. Endogenous serum nitrate (SNO3) levels were measured with Griess reagent in 1178 samples. Biopsies were performed as clinically indicated. Tacrolimus levels, urinary cultures, and renal function tests were done as per unit protocol. Results. Fifty recipients (mean +/- SD age 45.2 +/- 2.18 yrs, 24 men and 6 women) underwent 68 biopsies. Forty-five Bx (66.2%) showed AR in 19 recipients (mean age 47 +/- 8) and 23 (33.8%) Bx in 13 recipients (mean age 43 +/- 12) showed no AR. SNO3 in AR was (73 +/- 8.89 mu mol/L) compared with negative Bx (45 +/- 4.5 mu mol/L; P < 0.05). There was also a significant difference in SNO3 during AR and other causes of allograft dysfunction; delayed graft function (54 +/- 7.8 mu mol/L), urinary tract infection (44 +/- 2.9 mu mol/L), tacrolimus toxicity (51 +/- 2.86 mu mol/L), and increase in serum creatinine (44 +/- 2.36 mu mol/L). Conclusion. There is a significant increase of serum nitrate with episodes of acute rejection compared with other causes of renal dysfunction. SNO3 can therefore aid in the diagnosis of acute rejection.