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Determination of neopterin in urine, plasma, and serum is increasingly used in transplantation medicineas a sensitivemarker ofimmunologicalcomplications(forreviews,see 1-3). In a recent Technical Brief, Myara et al. (4) made a significant and important contribution to these issues; showing that, in recipients of heart allografts, simultaneous determination of concentrations of neopterin and of C-reactive protein in serum enables differentiation between bacterial and viral infections. One of their statements, however, deserves more detailed discussion: They state that concentrations of neopterin in serum are affected by renal dysfunction, and therefore are only of limited use in renal-transplant recipients. We (5, 6) and others (7-10) have shown that in case of renal impairment it is essential to relate concentrations of neopterin in serum to simultaneously measured concentrations of creatinine in serum ifone isto distinguish increases in neopterin due to cell-mediated immune activation from those simply caused by insufficient excretion.Notably,in our study (11) first proposing measurement of neopterin concentrations for diagnosis of rejection of kidney allografts, urine was used, and here, neopterin concentrations are routinely related to urinary creatinine. It was demonstrated that a strong linear relationship exists between clearance rates of neopterin and creatmine (linear correlation coefficient r = 0.863; 95% confidence interval 0.8410.882) with a regression coefficient of about 1.8 (7). Analogously, in healthy subjects neopterin clearance was found to be about 1.8 (6). Moreover, when serum neopterinconcentrations were related to urinary neopterinlcreatiine ratios (7), onlya weak correlation (r = 0.269; 0.190-0.345) was found, which was dramatically improved by relating serum neopterin to serum creatimne (r = 0.779;0.7500.805). Similarly, neopterin concentrations in serum were similar in patients with acute tubular necrosis and during acute rejection, but relating them to serum creatiine yielded a clear distinction between both diagnostic categories. Wolf et al. (8) found that the ratio of neopterin clearance and serum neopterin concentrations was superior for differential diagnosis between acute tubular necrosisand graft rejection. We conclude that it is imperative to relateconcentrationsin serum to one measure ofrenalfunction(most simply to serum creatinine concentration) in all conditions where renal impairment may occur-especially in renal transplantation, where large variability of renal function is met.

Concentrations of neopterin in serum of recipients of renal allografts.