Aldámiz-Echevarría Luis, Sanjurjo Pablo, Vallo Alfredo, Aguirre Mireia, Pérez-Nanclares Gustavo, Gimeno Pilar, Rueda Miguel, Ruiz José Ignacio, Rodríguez-Soriano Juan
Division of Metabolism, Department of Pediatrics, Hospital de Cruces and Basque University School of Medicine, Bilbao, País Vasco, Spain.
Pediatr Nephrol. 2003 Aug;18(8):749-55. doi: 10.1007/s00467-003-1157-6. Epub 2003 May 22.
Recent studies have shown that activity of plasminogen activator inhibitor-1 (PAI-1), a prothrombotic protein, may be increased in transplanted patients. The aim of the present investigation was to determine PAI-1 activity in pediatric recipients of renal transplants and to establish the relative contribution of both genetic and metabolic factors. In 29 children and adolescents with stable renal transplants, we related plasma PAI-1 activity to an indicator of inflammatory status [plasma concentration of C-reactive protein (CRP)] and to elements of the insulin resistance syndrome [body mass index (BMI), fasting insulinemia, HOMA index and plasma triglyceride, HDL-cholesterol, apolipoproteins A-1 and B concentrations]. Polymorphisms of PAI-1, apolipoprotein E (apoE) and angiotensin-converting enzyme (ACE) genes were also investigated. In all patients the study was repeated 1 year later. PAI-1 activity remained constantly elevated (23.4+/-22.8 and 18.6+/-7.8 U/ml in the first and second study, respectively, P=NS). Plasma PAI-1 activity correlated positively with CRP ( P=0.001), BMI z score ( P=0.02), fasting insulinemia ( P=0.009), and HOMA index ( P=0.006). No significant correlations were found in this population between plasma PAI-1 activity and age, gender, time elapsed after transplantation and plasma homocysteine, total cholesterol, LDL-cholesterol, HDL-cholesterol, apolipoprotein B, and apolipoprotein A-1. Plasma PAI-1 activity was not related to the cumulative dose of prednisone, cyclosporin A, or tacrolimus. Plasma PAI-1 activity was significantly higher in 5 children with apoE3/apoE4 genotype. No apparent influences of the PAI-1 4G/4G and ACE I/D genotypes were observed. In a multiple stepwise regression model, fasting insulinemia and apoE3/apoE4 genotype accounted for 45% of the observed plasma PAI-1 variability. We conclude that increased PAI-1 activity in children with stable renal transplants is determined both by genetic factors and by metabolic factors, the latter mainly linked to the insulin resistance syndrome.
近期研究表明，促血栓形成蛋白纤溶酶原激活物抑制剂-1（PAI-1）的活性在移植患者中可能会升高。本研究的目的是测定肾移植儿科受者的PAI-1活性，并确定遗传因素和代谢因素的相对作用。在29例肾移植稳定的儿童和青少年中，我们将血浆PAI-1活性与炎症状态指标[C反应蛋白（CRP）的血浆浓度]以及胰岛素抵抗综合征的指标[体重指数（BMI）、空腹胰岛素血症、HOMA指数以及血浆甘油三酯、高密度脂蛋白胆固醇、载脂蛋白A-1和B的浓度]相关联。我们还研究了PAI-1、载脂蛋白E（apoE）和血管紧张素转换酶（ACE）基因的多态性。1年后，对所有患者重复进行该研究。PAI-1活性持续升高（首次研究和第二次研究中分别为23.4±22.8和18.6±7.8 U/ml，P=无显著性差异）。血浆PAI-1活性与CRP（P=0.001）、BMI z评分（P=0.02）、空腹胰岛素血症（P=0.009）和HOMA指数（P=0.006）呈正相关。在该人群中，血浆PAI-1活性与年龄、性别、移植后经过的时间以及血浆同型半胱氨酸、总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、载脂蛋白B和载脂蛋白A-1之间未发现显著相关性。血浆PAI-1活性与泼尼松、环孢素A或他克莫司的累积剂量无关。5例apoE3/apoE4基因型的儿童血浆PAI-1活性显著更高。未观察到PAI-1 4G/4G和ACE I/D基因型有明显影响。在多元逐步回归模型中，空腹胰岛素血症和apoE3/apoE4基因型占观察到的血浆PAI-1变异性的45%。我们得出结论，肾移植稳定的儿童中PAI-1活性升高是由遗传因素和代谢因素共同决定的，后者主要与胰岛素抵抗综合征有关。
