Francis Mildred E, Eggers Paul W, Hostetter Thomas H, Briggs Josephine P
Social & Scientific Systems, Inc., Silver Spring, Maryland, USA.
Kidney Int. 2004 Jul;66(1):303-12. doi: 10.1111/j.1523-1755.2004.00732.x.
Circulating homocysteine, a risk factor for cardiovascular disease (CVD), is often elevated in chronic kidney disease and end-stage renal disease (ESRD) patients. Little is known about the risk of elevated homocysteine associated with less advanced renal insufficiency in the community.
Serum homocysteine concentration measures (umol/L) from the National Health and Nutrition Examination Survey (NHANES) 1991-1994 participants who were aged >/=40 years and fasted >/=6 hours (1558 men and 1829 women) were categorized as <9, 9 to 11.9, 12 to 14.9, and >/=15. Renal function levels were determined by Modified Diet in Renal Disease (MDRD) estimated glomerular filtration rate (GFRest) (mL/min/1.73 m(2)) and the urinary albumin-to-creatinine ratio (ACR) (mg/g). Cumulative odds ratios (OR) of exceeding any given homocysteine cut point were computed by gender, using ordinal logistic regression. Each model included GFRest (<60, 60 to 90, >/=90), ACR (<15, 15 to <30, >/=30), age, race/ethnicity, red blood cell folate, serum vitamin B(12), and dietary vitamin B(6) intake as independent variables.
The adjusted ORs for elevated homocysteine risk were 9 to 11 times greater in adults with the lowest GFRest levels (<60 mL/min/1.73 m(2)) compared to those with normal GFRest levels. Association measures for marginal GFRest levels (60 to 90 mL/min/1.73 m(2)) were weaker but significant. Albuminuria (ACR >/=30 mg/g) was a significant, independent renal risk factor for elevated homocysteine in men and women (adjusted OR = 1.78, 95% CI 1.08-2.93, and adjusted OR = 1.83, 95% CI 1.21-2.76, respectively) relative to those with low normal albumin excretion, but high normal albuminuria (ACR = 15-30 mg/g) was not.
In the general population, renal insufficiency is strongly associated with an increased risk of elevated circulating homocysteine, independent of B vitamin status. These results raise the possibility that elevated homocysteine may be an important risk factor to explain the heavy burden of CVD associated with kidney disease.
循环同型半胱氨酸是心血管疾病（CVD）的一个风险因素，在慢性肾脏病和终末期肾病（ESRD）患者中常升高。关于社区中不太严重的肾功能不全相关的同型半胱氨酸升高风险知之甚少。
对1991 - 1994年美国国家健康与营养检查调查（NHANES）中年龄≥40岁且禁食≥6小时的参与者（1558名男性和1829名女性）的血清同型半胱氨酸浓度测量值（μmol/L）进行分类，分为<9、9至11.9、12至14.9以及≥15。通过改良肾病饮食（MDRD）估计肾小球滤过率（GFRest）（mL/min/1.73 m²）和尿白蛋白与肌酐比值（ACR）（mg/g）来确定肾功能水平。使用有序逻辑回归按性别计算超过任何给定同型半胱氨酸切点的累积比值比（OR）。每个模型包括GFRest（<60、60至90、≥90）、ACR（<15、15至<30、≥30）、年龄、种族/民族、红细胞叶酸、血清维生素B12以及饮食中维生素B6摄入量作为自变量。
与GFRest水平正常的成年人相比，GFRest水平最低（<60 mL/min/1.73 m²）的成年人中同型半胱氨酸升高风险的校正OR高9至11倍。边缘GFRest水平（60至90 mL/min/1.73 m²）的关联度量较弱但显著。相对于白蛋白排泄量低正常的人，白蛋白尿（ACR≥30 mg/g）是男性和女性同型半胱氨酸升高的一个显著独立肾脏风险因素（校正OR分别为1.78，95%CI 1.08 - 2.93和校正OR为1.83，95%CI 1.21 - 2.76），但高正常白蛋白尿（ACR = 15 - 30 mg/g）不是。
在一般人群中，肾功能不全与循环同型半胱氨酸升高风险增加密切相关，与B族维生素状态无关。这些结果增加了同型半胱氨酸升高可能是解释与肾病相关的CVD沉重负担的一个重要风险因素的可能性。
