Boes Eva, Fliser Danilo, Ritz Eberhard, König Paul, Lhotta Karl, Mann Johannes F E, Müller Gerhard A, Neyer Ulrich, Riegel Werner, Riegler Peter, Kronenberg Florian
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Schöpfstrasse 41, A-6020 Innsbruck, Austria.
J Am Soc Nephrol. 2006 Feb;17(2):528-36. doi: 10.1681/ASN.2005070733. Epub 2005 Dec 28.
It has not been established firmly whether dyslipidemia contributes independently to the progression of kidney disease. Lipid and lipoprotein parameters, including levels of total, HDL, and LDL cholesterol; triglycerides; lipoprotein(a); apolipoprotein A-IV; and the apolipoprotein E and A-IV polymorphisms, were assessed in 177 patients who had mostly mild to moderate renal insufficiency and were followed prospectively for up to 7 yr. Progression of kidney disease was defined as doubling of baseline serum creatinine and/or terminal renal failure necessitating renal replacement therapy. In univariate analysis, patients who reached a progression end point (n = 65) were significantly older and had higher serum creatinine and proteinuria as well as lower GFR and hemoglobin levels. In addition, baseline apolipoprotein A-IV and triglyceride concentrations were higher and HDL cholesterol levels were lower. Multivariate Cox regression analysis revealed that baseline GFR (hazard ratio 0.714; 95% confidence interval [CI] 0.627 to 0.814 for an increment of 10 ml/min per 1.73 m(2); P < 0.0001) and serum apolipoprotein A-IV concentrations (hazard ratio 1.062; 95% CI 1.018 to 1.108 for an increment of 1 mg/dl; P = 0.006) were significant predictors of disease progression. Patients with apolipoprotein A-IV levels above the median had a significantly faster progression (P < 0.0001), and their mean follow-up time to a progression end point was 53.7 mo (95% CI 47.6 to 59.8) as compared with 70.0 mo (95% CI 64.6 to 75.4) in patients with apolipoprotein A-IV levels below the median. For the apolipoprotein E polymorphism, only the genotype epsilon2/epsilon4 was associated with an increased risk for progression. In summary, this prospective study in patients with nondiabetic primary kidney disease demonstrated that apolipoprotein A-IV concentration is a novel independent predictor of progression.
血脂异常是否独立促进肾脏疾病进展尚未得到确凿证实。对177例大多为轻至中度肾功能不全的患者进行了脂质和脂蛋白参数评估，包括总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇水平、甘油三酯、脂蛋白(a)、载脂蛋白A-IV以及载脂蛋白E和A-IV基因多态性，并对其进行了长达7年的前瞻性随访。肾脏疾病进展定义为基线血清肌酐翻倍和/或因终末期肾衰竭需要肾脏替代治疗。单因素分析显示，达到进展终点的患者（n = 65）年龄显著更大，血清肌酐、蛋白尿水平更高，肾小球滤过率（GFR）和血红蛋白水平更低。此外，基线载脂蛋白A-IV和甘油三酯浓度更高，高密度脂蛋白胆固醇水平更低。多因素Cox回归分析显示，基线GFR（每1.73 m²增加10 ml/min时，风险比为0.714；95%置信区间[CI]为0.627至0.814；P < 0.0001）和血清载脂蛋白A-IV浓度（每增加1 mg/dl，风险比为1.062；95% CI为1.018至1.108；P = 0.006）是疾病进展的显著预测因素。载脂蛋白A-IV水平高于中位数的患者进展明显更快（P < 0.0001），其至进展终点的平均随访时间为53.7个月（95% CI为47.6至59.8），而载脂蛋白A-IV水平低于中位数的患者为70.0个月（95% CI为64.6至75.4）。对于载脂蛋白E基因多态性，只有ε2/ε4基因型与进展风险增加相关。总之，这项针对非糖尿病原发性肾病患者的前瞻性研究表明，载脂蛋白A-IV浓度是进展的一个新的独立预测因素。
