Department of Medicine and Laboratory Services, Medical University of South Carolina and Ralph H. Johnson VA Medical Center, Charleston, SC, USA.
Nephrol Dial Transplant. 2012 Apr;27(4):1416-23. doi: 10.1093/ndt/gfr454. Epub 2011 Aug 19.
Modified low-density lipoprotein (LDL) immune complexes (IC) have proinflammatory properties and play a role in albuminuria development.
We measured oxidized LDL (oxLDL) and advanced glycation end-product (AGE)-LDL in IC isolated from sera of Type 1 diabetic subjects followed for 14-20 years and studied their association with abnormal albuminuria. Patients with albumin excretion rates (AER)<40 mg/24 h at baseline and follow-up (n=302) were deemed resistant to developing abnormal albuminuria. Patients with AER<40 mg/24 h at baseline whose AER levels progressed to >40 mg/24 h were considered prone to abnormal albuminuria (n=185), those who progress to AER>299 mg/24 h were considered as having macroalbuminuria (n=57). The odds of developing abnormal albuminuria were estimated by logistic regression based on natural log-transformed levels of oxLDL and AGE-LDL in IC and stratified by baseline AER decile.
OxLDL and AGE-LDL were significantly higher in IC isolated from patients progressing to abnormal albuminuria. In unadjusted conditional logistic analysis, an increase of 1 SD in oxLDL and AGE-LDL levels in IC significantly increased the odds ratio (OR) for development of macroalbuminuria, respectively, by a factor of 2.5 and 1.8 (P<0.001, P=0.008). The increased odds of developing macroalbuminuria remained significant when adjusted for treatment group, diabetes duration, retinopathy, baseline hemoglobin A1c and LDL (OR=2.5 and 1.8, respectively, P<0.01).
Higher levels of oxLDL and AGE-LDL in circulating IC were associated with increased odds to develop abnormal albuminuria.
修饰后的低密度脂蛋白（LDL）免疫复合物（IC）具有促炎作用，并在蛋白尿的发生发展中发挥作用。
我们测量了在随访 14-20 年后从 1 型糖尿病患者血清中分离出的 IC 中的氧化 LDL（oxLDL）和晚期糖基化终产物（AGE）-LDL，并研究了它们与异常蛋白尿的关系。基线和随访时尿白蛋白排泄率（AER）<40mg/24h 的患者（n=302）被认为对发展异常蛋白尿有抵抗性。基线时 AER<40mg/24h 但 AER 水平进展至>40mg/24h 的患者被认为易发生异常白蛋白尿（n=185），进展至 AER>299mg/24h 的患者被认为患有大量白蛋白尿（n=57）。根据 oxLDL 和 AGE-LDL 在 IC 中的自然对数转换水平，并按基线 AER 十分位数分层，通过逻辑回归估计发展异常白蛋白尿的可能性。
进展为异常白蛋白尿的患者 IC 中 oxLDL 和 AGE-LDL 明显升高。在未调整的条件逻辑分析中，IC 中 oxLDL 和 AGE-LDL 水平每增加 1 个标准差，发展为大量白蛋白尿的比值比（OR）分别增加 2.5 倍和 1.8 倍（P<0.001，P=0.008）。当调整治疗组、糖尿病病程、视网膜病变、基线血红蛋白 A1c 和 LDL 时，发展为大量白蛋白尿的可能性增加仍然显著（OR=2.5 和 1.8，P<0.01）。
循环 IC 中 oxLDL 和 AGE-LDL 水平升高与发生异常白蛋白尿的几率增加相关。
