晚期糖基化终末产物和氧化应激在慢性移植肾肾病中增加。

Advanced glycation end products and oxidative stress are increased in chronic allograft nephropathy.

作者信息

Raj Dominic S C, Lim Gideon, Levi Moshe, Qualls Clifford, Jain Sushil K

机构信息

Division of Nephrology, University of New Mexico, Albuquerque, NM, USA.

出版信息

Am J Kidney Dis. 2004 Jan;43(1):154-60. doi: 10.1053/j.ajkd.2003.09.021.

DOI:10.1053/j.ajkd.2003.09.021

PMID:14712439

Abstract

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 micromol/L]) and CAN (2.4 +/- 1.1 mg/dL [212.1 +/- 96.6 micromol/L]) than in controls (1.2 +/- 0.3 mg/dL [105.8 +/- 26.7 micromol/L]) and KPT patients (1.2 +/- 0.2 mg/dL [109.7 +/- 17.7 micromol/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/micromol 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 micromol 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.

摘要

背景

慢性移植肾肾病（CAN）的组织学表现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及肾脏疾病的进展有关。

方法

作者对11例肾功能正常的肾移植术后患者（KPT）和10例经活检证实为CAN的患者在移植后1、3、6、9至12个月以及18至24个月时连续检测血浆丙二醛（MDA）、羰基蛋白（CP）、戊糖苷和精氨嘧啶水平。还获取了16例对照者和13例慢性肾衰竭（CRF）患者的数据。

结果

尽管KPT患者在随访期间血清肌酐、MDA、CP、戊糖苷和精氨嘧啶水平下降，但CAN患者的这些指标却逐渐升高。CRF患者（3.3±0.8mg/dL[291.7±70.7μmol/L]）和CAN患者（2.4±1.1mg/dL[212.1±96.6μmol/L]）的平均血清肌酐水平高于对照者（1.2±0.3mg/dL[105.8±26.7μmol/L]）和KPT患者（1.2±0.2mg/dL[109.7±17.7μmol/L]；P<0.001）。移植后18至24个月时，CAN患者氧化应激和AGES的标志物高于KPT患者、对照者和CRF患者。与对照者（0.53±0.12）、KPT患者（0.52±0.15）和CRF患者（0.74±0.27）组相比，CAN患者的MDA（nmol/mL）显著更高（1.30±0.30；P<0.001）。在同一时间点，CAN患者的血浆CP（nmol/mg蛋白）（4.3±1.00）高于对照者（1.90±0.69）和KPT患者（2.62±1.00）组（P<0.001），但与CRF患者（2.69±1.20）相当。与对照者（2.49±0.86）、CRF患者（13.10±3.68）和KPT患者（14.32±6.28）组相比，CAN患者的血浆戊糖苷（pmol/μmol蛋白）水平更高（19.69±5.05；P<0.001）。与对照者（4.81±1.91）、CRF患者（56.92±29.67）和KPT患者（31.1±11.1；P<0.001）组相比，CAN患者的血浆精氨嘧啶（pmol/10μmol蛋白）更高（123.8±17.9）。