Chew S T, Newman M F, White W D, Conlon P J, Saunders A M, Strittmatter W J, Landolfo K, Grocott H P, Stafford-Smith M
Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA.
Anesthesiology. 2000 Aug;93(2):325-31. doi: 10.1097/00000542-200008000-00008.
Renal dysfunction after cardiac surgery occurs in up to 8% of patients and is associated with major increases in morbidity, mortality, and cost. Genetic polymorphisms have been implicated as a factor in the progression of chronic renal disease, but a genetic basis for the development of acute renal impairment has not been investigated. The authors therefore tested the hypothesis that apolipoprotein E alleles are associated with different postoperative changes in serum creatinine after cardiac surgery.
The authors performed a prospective observational study with use of data from 564 coronary bypass surgical patients who were enrolled in an ongoing investigation of apolipoprotein E genotypes and organ dysfunction at a university hospital between 1989-1999. Renal function was assessed among apolipoprotein E genotype groups by comparisons of preoperative (CrPre), peak in-hospital postoperative (CrMax) and perioperative change (DCr) in serum creatinine values.
The epsilon4 allele grouping (E2 = 2/2,2/3,2/4; E3 = 3/3; E4 = 3/4,4/4) was associated with a smaller increase in postoperative serum creatinine (perioperative change: E4, +0.17; E3, +0.26; E4, +0.27 mg/dl) and a lower peak postoperative creatinine than the epsilon2 and epsilon3 in univariate and multivariate analysis (peak in-hospital postoperative serum creatinine multivariate P = 0.015 vs. epsilon3, P = 0.038 vs. epsilon2). There was no difference in baseline creatinine among allele groups.
Inheritance of the apolipoprotein epsilon4 allele is associated with reduced postoperative increase in serum creatinine after cardiac surgery, compared with the epsilon3 or epsilon2 allele. This is the first report of a possible genetic basis for acute renal impairment. These data may contribute to renal risk stratification for cardiac surgery and raise questions regarding apolipoprotein E and the pathophysiology of acute renal injury.
心脏手术后肾功能不全在高达8%的患者中发生，并且与发病率、死亡率及费用的显著增加相关。基因多态性被认为是慢性肾脏疾病进展的一个因素，但急性肾损伤发生的遗传基础尚未得到研究。因此，作者检验了载脂蛋白E等位基因与心脏手术后血清肌酐不同术后变化相关的假设。
作者进行了一项前瞻性观察性研究，使用了1989年至1999年在一所大学医院进行的一项关于载脂蛋白E基因型和器官功能障碍的正在进行的研究中纳入的564例冠状动脉搭桥手术患者的数据。通过比较术前（CrPre）、术后住院期间峰值（CrMax）和围手术期血清肌酐值变化（DCr），在载脂蛋白E基因型组中评估肾功能。
在单因素和多因素分析中，ε4等位基因分组（E2 = 2/2、2/3、2/4；E3 = 3/3；E4 = 3/4、4/4）与术后血清肌酐较小的升高（围手术期变化：E4为+0.17；E3为+0.26；E4为+0.27mg/dl）以及比ε2和ε3更低的术后肌酐峰值相关（术后住院期间血清肌酐峰值多因素分析中，与ε3相比P = 0.015，与ε2相比P = 0.038）。等位基因组之间的基线肌酐没有差异。
与ε3或ε2等位基因相比，载脂蛋白ε4等位基因的遗传与心脏手术后血清肌酐术后升高的降低相关。这是急性肾损伤可能的遗传基础的首次报道。这些数据可能有助于心脏手术的肾脏风险分层，并引发关于载脂蛋白E和急性肾损伤病理生理学的问题。
