Urinary N-acetyl-beta-D-glucosaminidase and neopterin aid in the diagnosisof rejection and acute tubular necrosis in initially nonfunctioning kidneygrafts

Aim:The study aimed at investigating urinary neopterin, a marker of cellula r immune response, and urinary Nacetyl-beta-D-glucosaminidase (NAG), a mark er of tubular damage, as noninvasive means to differentiate between acute t ubular necrosis (ATN) and rejection in initially nonfunctioning (INF) human renal transplants. Methods: Seventy-two renal transplant patients were stu died. Forty-five of them experienced an uncomplicated early post-transplant course, 27 patients suffered from INF. Twenty-two patients experienced ATN , 5 patients had a total of six biopsy-proven rejections. The NAG activity was measured by a colorimetric assay, neopterin by high-performance liquid chromatography. Receiver operating characteristics (ROC) analysis was appli ed to compute diagnostic performance and an optimal discriminating threshol d. Results: Demographic characteristics (age, gender, cold and warm ischemi a periods, HLA mis-matches) and posttransplant urinary NAG and neopterin ex cretions did not differ between ATN and rejection groups. Both urinary NAG and neopterin excretions were lower in the control group (NAG 1.8 +/- 1.0 U /mmol urinary creatinine; neopterin 270 +/- 126 nmol/mmol urinary creatinin e; mean +/- SD) as compared with the ATN group (NAG 12 +/- 10 U/mmol, p < 0 .001 vs. control group; neopterin 303 +/- 195 nmol/mmol, n.s.) and the reje ction group (NAG 7 +/- 8 U/mmol, p < 0.01; neopterin 508 +/- 419 nmol/mmol, p < 0.01). The ratio of urinary neopterin to NAG excretion (uNNR; dimensio n nmol neopterin/U NAG activity) increased during rejections as compared wi th ATN (139 +/- 74 vs. 50 +/- 38 nmol/U, p < 0.01). The area under the ROC curve for uNNR was 0.88 +/- 0.07 (p < 0.001). Applying a ROC-estimated opti mal discriminator of uNNR (80 nmol/U), 16 patients with ATN and all six rej ection episodes were classified correctly. Conclusion: The uNNR provides a noninvasive means to aid in the differential diagnosis of rejection and ATN in INF human renal transplants. Copyright (C) 2000 S. Karger AG, Basel.