Hartog Jasper W L, Gross Sascha, Oterdoom Leendert H, van Ree Rutger M, de Vries Aiko P J, Smit Andries J, Schouten Jan P, Nawroth Peter P, Gans Reinold O B, van Son Willem J, Bierhaus Angelika, Bakker Stephan J L
Department of Internal Medicine, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands.
Transplantation. 2009 Apr 15;87(7):1069-77. doi: 10.1097/TP.0b013e31819d3173.
Skin-autofluorescence (skin-AF) noninvasively measures the tissue accumulation of advanced glycation end products (AGEs). AGEs are nephrotoxic and potential effectors of cardiovascular mortality. We investigated whether skin-AF predicted graft loss after kidney transplantation.
A total of 302 renal transplant recipients were enrolled at a median time of 6.1 (2.6-12.1) years after transplantation and were subsequently followed up for first occurrence of graft loss (i.e., graft failure or all-cause mortality) for 5.2 (4.6-5.4) years. The association of baseline skin-AF with graft loss was investigated with univariable and multivariable Cox-regression and receiver-operator-characteristic curve analyses.
Baseline skin-AF was 2.7+/-0.8 arbitrary units. Skin-AF predicted graft loss in a univariable Cox regression analysis (Hazard ratios 2.40 [1.75-3.29], P<0.001) and in a multivariable model (Hazard ratios 1.83 [1.22-2.75], P=0.003), adjusted for other identified risk-factors, including patient age, creatinine clearance, protein excretion, high sensitivity C-reactive protein (hsCRP), and human leukocyte antigen-DR mismatching. The area under the receiver-operator-characteristic curve for skin-AF as predictor of graft loss was significantly different from 0.5. Skin-AF was also a significant predictor of graft failure and mortality as separate end points.
We conclude that skin-AF is an independent predictor of graft loss in kidney transplant recipients. Although skin-AF is not a direct measurement for AGEs, we believe that our results do support the hypothesis that accumulation of AGEs in renal transplant recipients contributes to the development of graft loss.
皮肤自体荧光(skin-AF)可无创测量晚期糖基化终末产物(AGEs)在组织中的蓄积情况。AGEs具有肾毒性,是心血管疾病死亡的潜在影响因素。我们研究了皮肤-AF是否能预测肾移植后的移植物丢失情况。
共纳入302例肾移植受者,入组时移植后的中位时间为6.1(2.6 - 12.1)年,随后对其进行了5.2(4.6 - 5.4)年的随访,观察移植物丢失(即移植失败或全因死亡)的首次发生情况。采用单变量和多变量Cox回归以及受试者工作特征曲线分析,研究基线皮肤-AF与移植物丢失之间的关联。
基线皮肤-AF为2.7±0.8任意单位。在单变量Cox回归分析中(风险比2.40 [1.75 - 3.29],P<0.001)以及在多变量模型中(风险比1.83 [1.22 - 2.75],P = 0.003),经调整其他已确定的风险因素后,包括患者年龄、肌酐清除率、蛋白排泄、高敏C反应蛋白(hsCRP)以及人类白细胞抗原-DR错配情况,皮肤-AF可预测移植物丢失。皮肤-AF作为移植物丢失预测指标的受试者工作特征曲线下面积显著不同于0.5。皮肤-AF也是移植失败和死亡这两个独立终点的显著预测指标。
我们得出结论,皮肤-AF是肾移植受者移植物丢失的独立预测指标。虽然皮肤-AF并非对AGEs的直接测量,但我们认为我们的结果确实支持以下假设,即肾移植受者体内AGEs的蓄积促成了移植物丢失的发生。