Urinary N-Acetyl-β-<i>D</i>-Glucosaminidase and Neopterin Aid in the Diagnosis of Rejection and Acute Tubular Necrosis in Initially Nonfunctioning Kidney Grafts

Abstract

Aim: The study aimed at investigating urinary neopterin, a marker of cellular immune response, and urinary N-acetyl-β-D-glucosaminidase (NAG), a marker of tubular damage, as noninvasive means to differentiate between acute tubular necrosis (ATN) and rejection in initially nonfunctioning (INF) human renal transplants. Methods: Seventy-two renal transplant patients were studied. Forty-five of them experienced an uncomplicated early posttransplant 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 applied to compute diagnostic performance and an optimal discriminating threshold. Results: Demographic characteristics (age, gender, cold and warm ischemia periods, HLA mismatches) and posttransplant urinary NAG and neopterin excretions 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 creatinine; 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 rejection 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; dimension nmol neopterin/U NAG activity) increased during rejections as compared with 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 optimal discriminator of uNNR (80 nmol/U), 16 patients with ATN and all six rejection 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.

Relations between Concentrations of Asymmetric Dimethylarginine and Neopterin as Potential Risk Factors for Cardiovascular Diseases in Haemodialysis-Treated Patients

“…[21,22] The biosynthesis of neopterin starts from purinic guanosine triphosphate base that is converted to 7,8-dihydroneopterintriphosphate by GTP ciclohydrolase I. [23] NP levels rise in many pathologic conditions: renal failure [24] ; diabetic nephropathy [25] ; glomerulonephritis [26,27] ; renal transplant rejection [28] ; insulin resistance [29] ; autoimmune diseases [30] ; viral, [31] bacterial, [32] and protozoic infections [33] ; coronary artery disease [34] ; and psoriasis. [35] In humans, there is a correlation between serum NP concentration and the extent of atherosclerosis.…”

Gamma Interferon Is Dispensable for Neopterin Production In Vivo

“…In Austria, blood donations have been screened for elevated neopterin concentrations since 1994, and those with elevated neopterin concentrations are excluded from transfusion (12). Neopterin levels also rise in patients with autoimmune diseases (35), transplant rejection (22), and malignant diseases (23). It was shown previously that human macrophages and dendritic cells release neopterin into culture supernatants and that gamma interferon (IFN-␥) is the major factor inducing this phenomenon (18).…”

Calcineurin Inhibitors and Proximal Renal Tubular Injury in Renal Transplant Patients with Proteinuria and Chronic Allograft Nephropathy

“…Measurement of urinary NAG in renal transplant patients has more commonly been used to identify acute proximal tubular damage in acute transplant rejection and tubular necrosis (9,10). Data are limited in renal transplant recipients with proteinuria and CAN.…”

“…Urinary NAG has more commonly been measured in renal transplant recipients soon after transplantation to predict acute rejection or tubular necrosis (9,10). Data are limited in patients on CI many years posttransplantation (11,12).…”