Advanced glycation end products and oxidative stress are increased in chronic allograft nephropathy
Advanced glycation end products and oxidative stress are increased in chronic allograft nephropathy
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DOI：
10.1053/j.ajkd.2003.09.021
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发表时间：
2004-01-01
影响因子：
13.2
通讯作者：
Jain, SK
中科院分区：
文献类型：
--
作者：
Raj, DSC;Lim, G;Jain, SK
背景。慢性同种异体移植肾病（CAN）的组织学图像类似于早期动脉硬化病变。氧化应激和晚期糖基化终产物（AGES）与动脉粥样硬化的发病机制和肾脏疾病的进展有关。方法：作者在肾移植后1、3、6、9至12、18至24个月连续测定11例肾功能正常（KPT）患者和10例活检证实CAN患者的血浆丙二醛（MDA）、羰基蛋白（CP）、戊sidine和argpyramidine水平。还获得了16名对照组和13名慢性肾功能衰竭（CRF）患者的数据。结果：虽然KPT患者的血清肌酐、丙二醛、CP、戊苷和阿氏嘧啶水平在随访期间下降，但在CAN患者中逐渐升高。CRF患者（3.3 +/- 0.8 mg/dL [291.7 +/- 70.7 mumol/L]）和CAN患者（2.4 +/- 1.1 mg/dL [212.1 +/- 96.6 mumol/L]）的平均血清肌酐水平高于对照组（1.2 +/- 0.3 mg/dL [105.8 +/- 26.7 mumol/L]）和KPT患者（1.2 +/- 0.2 mg/dL [109.7 +/- 17.7 mumol/L], P < 0.001）。移植后18至24个月，CAN患者的氧化应激和AGEs指标高于KPT、对照组和CRF患者。与对照组（0.53 +/- 0.12）、KPT组（0.52 +/- 0.15）和CRF组（0.74 +/- 0.27）相比，CAN组MDA (nmol/mL)（1.30 +/- 0.30）显著升高（P < 0.001）。在同一时间点，CAN患者的血浆CP (nmol/mg protein)（4.3 +/- 1.00）高于对照组（1.90 +/- 0.69）和KPT组（2.62 +/- 1.00）（P < 0.001），但与CRF组（2.69 +/- 1.20）相当。与对照组（2.49 +/- 0.86）、CRF组（13.10 +/- 3.68）、KPT组（14.32 +/- 6.28）相比，CAN组血浆戊sidine （pmol/mu mol protein）水平（19.69 +/- 5.05）显著升高（P < 0.001）。与对照组（4.81 +/- 1.91）、CRF组（56.92 +/- 29.67）和KPT组（31.1 +/- 11.1;P < 0.001）相比，CAN患者血浆argpy嘧啶（pmol/10 mumol蛋白）（123.8 +/- 17.9）更高。结论：CAN患者氧化应激和AGEs升高，不能单纯用肾功能下降来解释。氧化应激和AGEs可能是CAN的非免疫介质之一。
Background. The histologic picture of chronic allograft nephropathy (CAN) resembles early arteriosclerotic lesion. Oxidative stress and advanced glycation end products (AGES) have been implicated in the pathogenesis of atherosclerosis and progression of renal disease. Methods: The authors serially measured the plasma malonyldialdehyde (MDA), carbonyl protein (CP), pentosidine, and argpyramidine levels in 11 postrenal transplant patients with normal renal function (KPT) and 10 patients with biopsy proven CAN at 1, 3, 6, 9 through 12, and 18 through 24 months posttransplant. Data were also obtained in 16 controls and 13 patients with chronic renal failure (CRF). Results: Although serum creatinine, MDA, CP, pentosidine, and argpyrimidine levels decreased during follow-up in KPT, it progressively increased in patients with CAN. The mean serum creatinine level was higher in patients with CRF (3.3 +/- 0.8 mg/dL [291.7 +/- 70.7 mumol/L]) and CAN (2.4 +/- 1.1 mg/dL [212.1 +/- 96.6 mumol/L]) than in controls (1.2 +/- 0.3 mg/dL [105.8 +/- 26.7 mumol/L]) and KPT patients (1.2 +/- 0.2 mg/dL [109.7 +/- 17.7 mumol/L]; P < 0.001). Markers of oxidative stress and AGEs measured at 18 to 24 months posttransplant in patients with CAN were higher than in KPT, controls, and CRF patients. MDA (nmol/mL) was significantly higher in patients with CAN (1.30 +/- 0.30) compared with controls (0.53 +/- 0.12), KPT (0.52 +/- 0.15), and CRF (0.74 +/- 0.27) groups (P < 0.001). Plasma CP (nmol/mg protein) in patients with CAN (4.3 +/- 1.00) was higher than in controls (1.90 +/- 0.69) and KPT (2.62 +/- 1.00) groups at the same time-point (P < 0.001), but comparable with CRF (2.69 +/- 1.20). Plasma pentosidine (pmol/mu mol protein) level in patients with CAN (19.69 +/- 5.05) was higher compared with controls (2.49 +/- 0.86), CRF (13.10 +/- 3.68), and KPT (14.32 +/- 6.28) groups (P < 0.001). Plasma argpyrimidine (pmol/10 mumol protein) was higher in patients with CAN (123.8 +/- 17.9) compared with controls (4.81 +/- 1.91), CRF (56.92 +/- 29.67), and KPT (31.1 +/- 11.1; P < 0.001) groups. Conclusion: Oxidative stress and AGEs are increased in patients with CAN, which cannot be explained by the decline in renal function alone. Oxidative stress and AGEs may be one among the nonimmune mediators of CAN.