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血清钙化抑制蛋白水平与冠状动脉钙化积分:移植与透析的比较

Serum levels of calcification inhibition proteins and coronary artery calcium score: comparison between transplantation and dialysis.

作者信息

Mazzaferro Sandro, Pasquali Marzia, Pugliese Francesco, Barresi Giusi, Carbone Iacopo, Francone Marco, Sardella Daniela, Taggi Franco

机构信息

Division of Nephrology, Department of Clinical Science, University of Rome La Sapienza, Rome, Italy.

出版信息

Am J Nephrol. 2007;27(1):75-83. doi: 10.1159/000099095. Epub 2007 Jan 26.

Abstract

Vascular calcifications in CKD are now linked to serum alterations of both divalent ions and calcification inhibitory proteins. Due to possible biochemical differences between dialysis (D) and transplantation (Tx), we examined the entity and severity of these biochemical modifications and of coronary artery calcium score separately in these two populations. We assayed, besides standard markers of inflammation, divalent ions and serum levels of fetuin, matrix Gla protein (MGP) and osteoprotegerin (OPG), in 51 Tx patients (age 45 +/- 12 years; 30 males, 21 females; previous D duration 4.8 +/- 4.2 years; Tx since 6.6 +/- 5.5 years; Cr 1.8 +/- 0.6 mg/dl) and in 49 D patients (age 49 +/- 14 years; 30 males,19 females; D duration 5.6 +/- 4.8 years). Additionally, coronary calcium score (AS) was evaluated by cardiac multi-slice CT. Compared with D patients, Tx patients had better values of divalent ions and inflammation markers, and lower prevalence (65 vs. 86%; p < 0.02) and severity (AS = 570 +/- 1,637 vs. 1,311 +/- 3,128; p < 0.008) of coronary calcification. In addition, a tendency toward normalization for all of the three calcification inhibitory proteins was evident. In both Tx and D, AS correlated with age and OPG (Tx: r(s) = 0.439, p < 0.001, and r(s) = 0.510, p < 0.0001; D: r(s) = 0.471, p < 0.001, and r(s) = 0.403, p < 0.005, respectively); in D patients, a correlation was present also with D duration (r(s) = 0.435; p < 0.002), other markers of inflammation and, notably, fetuin (r(s) = -0.442; p < 0.002). Regression analysis selected previous time on D in Tx patients (r(m) = 0.400; p < 0.004), and C-reactive protein and OPG in D patients (r(m) = 0.518; p < 0.004) as the most predictive parameters of AS. Discriminant analysis confirmed the major role of age and D duration in the appearance of AS and evidenced male gender as a distinct risk condition. At variance, Tx duration was never associated with AS. In conclusion, as compared to D, renal Tx patients show serum levels of calcification inhibition proteins and of divalent ions closer to normal. As this is associated with a lower prevalence and severity of AS, it is suggested that Tx antagonize the accelerating role of D in the progression of vascular calcification. Assessment of both coronary calcifications and serum levels of calcification inhibitory proteins may be of value to identify those subjects at higher risk of development and progression of vascular lesions, among whom males have the highest rate.

摘要

慢性肾脏病(CKD)中的血管钙化现在与二价离子和钙化抑制蛋白的血清改变有关。由于透析(D)和移植(Tx)之间可能存在生化差异,我们分别在这两个人群中检查了这些生化改变的情况以及冠状动脉钙化评分的严重程度。除了炎症的标准标志物外,我们还检测了51例移植患者(年龄45±12岁;男性30例,女性21例;既往透析时间4.8±4.2年;移植后6.6±5.5年;血肌酐1.8±0.6mg/dl)和49例透析患者(年龄49±14岁;男性30例,女性19例;透析时间5.6±4.8年)的二价离子以及胎球蛋白、基质Gla蛋白(MGP)和骨保护素(OPG)的血清水平。此外,通过心脏多层CT评估冠状动脉钙化评分(AS)。与透析患者相比,移植患者的二价离子和炎症标志物水平更好,冠状动脉钙化的患病率(65%对86%;p<0.02)和严重程度(AS=570±1637对1311±3128;p<0.008)更低。此外,三种钙化抑制蛋白均有趋于正常化的趋势。在移植和透析患者中,AS均与年龄和OPG相关(移植患者:r(s)=0.439,p<0.001,r(s)=0.510,p<0.0001;透析患者:r(s)=0.471,p<0.001,r(s)=0.403,p<0.005);在透析患者中,AS还与透析时间(r(s)=0.435;p<0.002)、其他炎症标志物,尤其是胎球蛋白(r(s)=-0.442;p<0.002)相关。回归分析选择移植患者既往透析时间(r(m)=0.400;p<0.004)以及透析患者的C反应蛋白和OPG(r(m)=0.518;p<0.004)作为AS的最具预测性的参数。判别分析证实年龄和透析时间在AS出现中起主要作用,并证明男性是一种明显的风险因素。不同的是,移植时间与AS从未相关。总之,与透析相比,肾移植患者的钙化抑制蛋白和二价离子血清水平更接近正常。由于这与较低的AS患病率和严重程度相关,提示移植可拮抗透析在血管钙化进展中的加速作用。评估冠状动脉钙化和钙化抑制蛋白的血清水平可能有助于识别血管病变发生和进展风险较高的人群,其中男性发生率最高。

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