Nephrology, Hospital Lucus Augusti, Lugo, Spain.
Nephrology, Hospital da Costa, Lugo, Spain.
PLoS One. 2018 Aug 1;13(8):e0201118. doi: 10.1371/journal.pone.0201118. eCollection 2018.
Advanced glycation end products (AGEs) accumulation, a measure of cumulative metabolic stress, constitute a novel pathogenic mechanism involved in aging, diabetes, cardiovascular (CVD) and chronic kidney disease (CKD). Despite removal of uremic toxins and AGEs after a successful renal transplant (RT), CVD remains the leading cause of mortality. We hypothesized that AGEs measurement by Skin Autofluorescence (SAF) might be useful even after a successful RT and thus reflect the high cardiovascular risk burden of these patients.
189 stable RT (61% men, aged 56±13.0 years), CKD stages 1-4 and >12 months since RT were enrolled. Variables collected comprised comorbid history, medication use, smoking habit, routine biochemistry, subclinical atheromatosis by ankle-brachial-index (ABI) and allograft resistivity index (RI), 24-h ABPM, anthropometry and handgrip strength. AGEs were measured by SAF and expressed in arbitrary units (AU). Vascular age was estimated by Koetsier´s formula (SAF-0.83/0.024) and expected 10-years cardiovascular death risk was calculated with the REGICOR score.
Mean SAF was 3.00±0.83 AU and estimated vascular age 90±34.7 years (30 years above biological age). SAF was higher among men (3.10±0.91 vs 2.81±0.66), diabetic nephropathy (3.49±0.75 vs 2.96±0.83) and steroid users (3.14±0.86 vs 2.71±0.69). We observed a positive correlation of SAF with night-systolic blood pressure (r = 0.25, p = 0.001), parathormone (r = 0.20, p<0.01), phosphate (r = 0.28, p<0.001) and negative with hemoglobin (r = -0.29, p<0.001), CKD-EPI (r = -0.32, p<0.001), albumin (r = -0.17, p<0.05), and dynamometry (r = -0.20, p<0.01). Subclinical vascular atheromatosis (ABI and RI) as well as the REGICOR scale (r = 0.35 p<0.001) were also correlated with SAF. In multivariable analysis age, gender, steroid use, serum phosphate and handgrip strength remained independently associated with SAF.
SAF levels are elevated in RT patients and correlate with CVD risk. Besides age and male sex, our results suggest that phosphate overload, steroid use and nutritional status are important factors linking to AGEs accumulation.
晚期糖基化终产物（AGEs）的积累是衡量累积代谢应激的指标，是衰老、糖尿病、心血管疾病（CVD）和慢性肾病（CKD）的新发病理机制。尽管在成功进行肾移植（RT）后清除了尿毒症毒素和 AGEs，但 CVD 仍然是导致死亡的主要原因。我们假设，即使在成功的 RT 后，通过皮肤自发荧光（SAF）测量 AGEs 可能仍然有用，因此可以反映这些患者的心血管高风险负担。
纳入 189 例稳定的 RT（61%为男性，年龄 56±13.0 岁）、CKD 1-4 期和 RT 后>12 个月的患者。收集的变量包括合并症病史、药物使用、吸烟习惯、常规生化指标、踝臂指数（ABI）和同种异体阻力指数（RI）的亚临床动脉粥样硬化、24 小时 ABPM、人体测量学和握力。通过 SAF 测量 AGEs，并以任意单位（AU）表示。血管年龄通过 Koetsier 公式（SAF-0.83/0.024）估算，使用 REGICOR 评分计算预期 10 年心血管死亡风险。
平均 SAF 为 3.00±0.83 AU，估计血管年龄为 90±34.7 岁（比生物学年龄大 30 岁）。男性（3.10±0.91 比 2.81±0.66）、糖尿病肾病（3.49±0.75 比 2.96±0.83）和类固醇使用者（3.14±0.86 比 2.71±0.69）的 SAF 更高。我们观察到 SAF 与夜间收缩压（r = 0.25，p = 0.001）、甲状旁腺激素（r = 0.20，p<0.01）、磷酸盐（r = 0.28，p<0.001）呈正相关，与血红蛋白（r = -0.29，p<0.001）、CKD-EPI（r = -0.32，p<0.001）、白蛋白（r = -0.17，p<0.05）和握力（r = -0.20，p<0.01）呈负相关。亚临床血管粥样硬化（ABI 和 RI）以及 REGICOR 量表（r = 0.35，p<0.001）也与 SAF 相关。多变量分析显示，年龄、性别、类固醇使用、血清磷酸盐和握力与 SAF 独立相关。
RT 患者的 SAF 水平升高，并与 CVD 风险相关。除年龄和性别外，我们的结果还表明，磷酸盐超负荷、类固醇使用和营养状况是与 AGEs 积累相关的重要因素。
