Parsons Darren S, Reaveley David A, Pavitt Darrell V, Brown Edwina A
Department of Renal Medicine, Faculty of Medicine, Imperial College School of Science, Technology and Medicine, Charing Cross Hospital, London, UK.
Am J Kidney Dis. 2002 Nov;40(5):916-23. doi: 10.1053/ajkd.2002.36321.
Total homocysteine (tHcy) and lipoprotein(a) [Lp(a)] levels have been recognized as risk factors for vascular disease. The combination of elevated tHcy and Lp(a) levels may be particularly atherogenic, although no study has examined the prevalence of the combination of both risk factors in patients with chronic renal impairment.
One hundred ninety-seven patients with renal impairment were studied. Patients had glomerular filtration rate (GFR) measured by clearance of chromium 51-labeled EDTA. Blood was obtained for the determination of tHcy, Lp(a), and apolipoprotein(a) [apo(a)] isoform levels.
Patients were divided into five groups according to GFR. Mean tHcy levels in the five groups were as follows: GFR less than 10 mL/min, 30.2 +/- 9.8 (SD) micromol/L; GFR of 10 to 20 mL/min, 26.6 +/- 10.5 micromol/L; GFR of 20 to 30 mL/min, 23.9 +/- 8.6 micromol/L; GFR of 30 to 45 mL/min, 22.2 +/- 8.6 micromol/L; and GFR of 45 to 75 mL/min, 18.2 +/- 9.1 micromol/L compared with control levels of 12.7 +/- 4.6 micromol/L. There was a progressive increase in median Lp(a) levels with declining renal function: median Lp(a) levels for those with a GFR less than 10 mL/min were 37.1 mg/dL (range, 0.6 to 156.0 mg/dL); GFR of 10 to 20 mL/min, 30.3 mg/dL (range, 2.6 to 163.7 mg/dL); GFR of 20 to 30 mL/min, 26.1 mg/dL (range, 0.0 to 164.0 mg/dL); GFR of 30 to 45 mL/min, 20.9 mg/dL (range, 0.0 to 99.8 mg/dL), and GFR of 45 to 75 mL/min, 16.8 mg/dL (range, 2.1 to 81.0 mg/dL) compared with control values of 12.5 mg/dL (range, 0.0 to 88.7 mg/dL).
Defining hyperhomocysteinemia as tHcy levels greater than the 90th percentile of controls and elevated Lp(a) level as greater than 30 mg/dL, the frequency of the combination increased with declining renal function. Fifty-eight percent of patients with a GFR less than 10 mL/min had both hyperhomocysteinemia and elevated Lp(a) levels, and even in patients with mild renal impairment, 20% of patients had both risk factors present.
总同型半胱氨酸（tHcy）和脂蛋白（a）[Lp（a）]水平已被确认为血管疾病的危险因素。tHcy和Lp（a）水平升高的联合作用可能具有特别强的致动脉粥样硬化作用，尽管尚无研究调查慢性肾功能损害患者中这两种危险因素联合存在的患病率。
对197例肾功能损害患者进行了研究。通过51铬标记的依地酸清除率测定患者的肾小球滤过率（GFR）。采集血液以测定tHcy、Lp（a）和载脂蛋白（a）[apo（a）]异构体水平。
根据GFR将患者分为五组。五组的平均tHcy水平如下：GFR低于10 mL/分钟，30.2±9.8（标准差）微摩尔/升；GFR为10至20 mL/分钟，26.6±10.5微摩尔/升；GFR为20至30 mL/分钟，23.9±8.6微摩尔/升；GFR为30至45 mL/分钟，22.2±8.6微摩尔/升；GFR为45至75 mL/分钟，18.2±9.1微摩尔/升，而对照组水平为12.7±4.6微摩尔/升。随着肾功能下降，Lp（a）水平中位数逐渐升高：GFR低于10 mL/分钟者的Lp（a）水平中位数为37.1毫克/分升（范围为0.6至156.0毫克/分升）；GFR为10至20 mL/分钟，30.3毫克/分升（范围为2.6至163.7毫克/分升）；GFR为20至30 mL/分钟，26.1毫克/分升（范围为0.0至164.0毫克/分升）；GFR为30至45 mL/分钟，20.9毫克/分升（范围为0.0至99.8毫克/分升），GFR为45至75 mL/分钟，16.8毫克/分升（范围为2.1至81.0毫克/分升），而对照组值为12.5毫克/分升（范围为0.0至88.7毫克/分升）。
将高同型半胱氨酸血症定义为tHcy水平高于对照组第90百分位数，将Lp（a）水平升高定义为高于30毫克/分升，随着肾功能下降，两者联合出现的频率增加。GFR低于10 mL/分钟的患者中有58%同时存在高同型半胱氨酸血症和Lp（a）水平升高，即使在轻度肾功能损害患者中，也有20%的患者同时存在这两种危险因素。
