In the underlying study the diagnostic value of the anaphylatoxin C5a was evaluated in kidney transplantation. In 49 transplant patients the following parameters were measured daily for a mean period of 25.1 days: plasma C5a [P-C5a], urine C5a [U-C5a], serum amyloid A [SAA], serum neopterin [S-NEOP] and urine neopterin [U-NEOP]. Sensitivity, specificity and day of first significant parameter increase (exceeding a cut-off level of > 50%) were evaluated retrospectively during 30 periods of rejection and 30 periods of stable graft function. U-C5a was the parameter with the highest sensitivity (84%) and specificity (84%), increasing in the mean 1.3 days before clinical diagnosis of rejection. Sensitivity and specificity of the other markers was lower: SAA 77% and 77%, U-NEOP 68% and 65%, S-NEOP 45% and 77%, and P-C5a 45% and 48%, respectively. During four instances of cytomegalovirus disease extremely high U-NEOP (> or = 1520 +/- 518 mumol/mol creatinine) and slightly increased P-C5a levels (> or = 1.5 +/- 1.4 ng/ml) occurred. Elevated urinary excretion of C5a seems to be a reliable and early marker of renal allograft rejection. In combination with SAA and U-NEOP, the daily assessment of U-C5a differentiates between viral infection and allograft rejection.