Moody William E, Ferro Charles J, Edwards Nicola C, Chue Colin D, Lin Erica Lai Sze, Taylor Robin J, Cockwell Paul, Steeds Richard P, Townend Jonathan N
From the Birmingham Cardio-Renal Group, Institute of Cardiovascular Science, Departments of Cardiology (W.E.M., N.C.E., C.D.C., E.L.S.L., R.J.T., R.P.S., J.N.T.) and Nephrology (C.J.F., P.C.), Queen Elizabeth Hospital Birmingham and University of Birmingham, Edgbaston, United Kingdom.
Hypertension. 2016 Feb;67(2):368-77. doi: 10.1161/HYPERTENSIONAHA.115.06608.
There is a robust inverse graded association between glomerular filtration rate (GFR) and cardiovascular risk, but proof of causality is lacking. Emerging data suggest living kidney donation may be associated with increased cardiovascular mortality although the mechanisms are unclear. We hypothesized that the reduction in GFR in living kidney donors is associated with increased left ventricular mass, impaired left ventricular function, and increased aortic stiffness. This was a multicenter, parallel group, blinded end point study of living kidney donors and healthy controls (n=124), conducted from March 2011 to August 2014. The primary outcome was a change in left ventricular mass assessed by magnetic resonance imaging (baseline to 12 months). At 12 months, the decrease in isotopic GFR in donors was -30±12 mL/min/1.73m(2). In donors compared with controls, there were significant increases in left ventricular mass (+7±10 versus -3±8 g; P<0.001) and mass:volume ratio (+0.06±0.12 versus -0.01±0.09 g/mL; P<0.01), whereas aortic distensibility (-0.29±1.38 versus +0.28±0.79×10(-3) mm Hg(-1); P=0.03) and global circumferential strain decreased (-1.1±3.8 versus +0.4±2.4%; P=0.04). Donors had greater risks of developing detectable highly sensitive troponin T (odds ratio, 16.2 [95% confidence interval, 2.6-100.1]; P<0.01) and microalbuminuria (odds ratio, 3.8 [95% confidence interval, 1.1-12.8]; P=0.04). Serum uric acid, parathyroid hormone, fibroblast growth factor-23, and high-sensitivity C-reactive protein all increased significantly. There were no changes in ambulatory blood pressure. Change in GFR was independently associated with change in left ventricular mass (R(2)=0.28; P=0.01). These findings suggest that reduced GFR should be regarded as an independent causative cardiovascular risk factor.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01028703.
肾小球滤过率(GFR)与心血管风险之间存在显著的反向分级关联,但因果关系尚缺乏证据。新出现的数据表明,活体肾捐赠可能与心血管死亡率增加有关,尽管其机制尚不清楚。我们推测,活体肾捐赠者GFR的降低与左心室质量增加、左心室功能受损和主动脉僵硬度增加有关。这是一项多中心、平行组、盲终点的研究,研究对象为活体肾捐赠者和健康对照者(n = 124),研究时间为2011年3月至2014年8月。主要结局是通过磁共振成像评估的左心室质量变化(基线至12个月)。12个月时,捐赠者的同位素GFR下降了-30±12 mL/min/1.73m²。与对照组相比,捐赠者的左心室质量(+7±10 g对-3±8 g;P<0.001)和质量:体积比(+0.06±0.12 g/mL对-0.01±0.09 g/mL;P<0.01)显著增加,而主动脉扩张性(-0.29±1.38×10⁻³ mmHg⁻¹对+0.28±0.79×10⁻³ mmHg⁻¹;P = 0.03)和整体圆周应变降低(-1.1±3.8%对+0.4±2.4%;P = 0.04)。捐赠者发生可检测到的高敏肌钙蛋白T(比值比,16.2 [95%置信区间,2.6 - 100.1];P<0.01)和微量白蛋白尿(比值比,3.8 [95%置信区间,1.1 - 12.8];P = 0.04)的风险更高。血清尿酸、甲状旁腺激素、成纤维细胞生长因子-23和高敏C反应蛋白均显著增加。动态血压无变化。GFR的变化与左心室质量的变化独立相关(R² = 0.28;P = 0.01)。这些发现表明,GFR降低应被视为心血管风险的独立致病因素。