Bello Aminu K, de Zeeuw Dick, El Nahas Meguid, Brantsma Auke H, Bakker Stephan J L, de Jong Paul E, Gansevoort Ronald T
Division of Nephrology, Department of Medicine, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.
Nephrol Dial Transplant. 2007 Jun;22(6):1619-27. doi: 10.1093/ndt/gfm091. Epub 2007 Mar 14.
Increased levels of albuminuria have been recognized as a feature of obesity and the metabolic syndrome, and to be associated with an increased risk for cardiovascular and renal disease. The impact of weight change on albuminuria and its possible mechanism has not been studied yet in the general population. We investigated this issue in a cohort of the Northern European population.
A total of 6894 participants of the Prevention of Renal and Vascular Endstage Disease (PREVEND) study were evaluated from baseline to a mean period of follow-up of 4.2 years for weight change (gain/loss), and its impact on albuminuria, renal function and cardiovascular risk factors. Participants were categorized into three groups based on absolute change in weight from baseline to follow-up: significant weight loss (>10 kg reduction in weight), stable weight, or significant weight gain (>10 kg increase). Multivariate regression analysis was used to evaluate the effect of baseline characteristics and time-dependent changes in these characteristics on the relationship of weight change with urine albumin excretion (UAE).
At follow-up 101 subjects experienced significant weight loss (mean change = -14.2 kg), 348 had significant weight gain (mean change = +13.4 kg) and the remaining were defined stable in weight (mean change = +1.4 kg). Weight loss was associated with significant improvement in systolic blood pressure (-11 +/- 15 mmHg), diastolic blood pressure (-5 +/- 8 mmHg), and cholesterol (-0.7 +/- 1.3 mmol/l), even after adjustment for the use of medications (P < 0.001). These parameters worsened significantly in those who substantially gained weight (P < 0.001). Similarly, weight loss was significantly associated with a reduction in UAE (mean -2.2 +/- 1.1 mg/24 h), whereas weight gain was associated with a rise in UAE (mean +0.42 +/- 2.0 mg/24 h). Notably, no changes were observed in GFR (assessed as 24 h urinary creatinine clearance) in subjects with weight loss or weight gain. Multivariate regression modelling with changes in UAE as dependent variable-correcting for factors that might explain the association-showed that only part of the relationship between weight changes and changes in UAE was explained by effect of weight change on blood pressure and cholesterol, whereas the association disappeared with changes in CRP in the model (P = 0.50).
This is the first population-based longitudinal study to show that changes in weight are associated with parallel changes in albuminuria. This relationship cannot be fully explained by the association between weight and classical cardiovascular risk factors and renal function. Based on our data we hypothesize that weight-induced changes in vascular inflammation may cause changes in albuminuria.
蛋白尿水平升高已被认为是肥胖和代谢综合征的一个特征,并且与心血管疾病和肾脏疾病风险增加相关。体重变化对蛋白尿的影响及其可能机制在普通人群中尚未得到研究。我们在一组北欧人群队列中调查了这个问题。
对预防终末期肾病(PREVEND)研究的总共6894名参与者从基线到平均4.2年的随访期进行评估,以了解体重变化(增加/减少)及其对蛋白尿、肾功能和心血管危险因素的影响。根据从基线到随访的体重绝对变化,将参与者分为三组:显著体重减轻(体重减轻>10 kg)、体重稳定或显著体重增加(体重增加>10 kg)。使用多变量回归分析来评估基线特征以及这些特征随时间的变化对体重变化与尿白蛋白排泄(UAE)关系的影响。
在随访时,101名受试者经历了显著体重减轻(平均变化=-14.2 kg),348名受试者体重显著增加(平均变化=+13.4 kg),其余受试者体重定义为稳定(平均变化=+1.4 kg)。即使在调整药物使用后,体重减轻与收缩压(-11±15 mmHg)、舒张压(-5±8 mmHg)和胆固醇(-0.7±1.3 mmol/l)的显著改善相关(P<0.001)。在体重大幅增加的受试者中,这些参数显著恶化(P<0.001)。同样,体重减轻与UAE显著降低显著相关(平均-2.2±1.1 mg/24 h),而体重增加与UAE升高相关(平均+0.42±2.0 mg/24 h)。值得注意的是,体重减轻或体重增加的受试者中,肾小球滤过率(以24小时尿肌酐清除率评估)未观察到变化。以UAE变化作为因变量进行多变量回归建模——校正可能解释这种关联的因素——结果显示,体重变化与UAE变化之间的关系只有部分是由体重变化对血压和胆固醇的影响所解释的,而在模型中随着CRP变化这种关联消失(P = 0.50)。
这是第一项基于人群的纵向研究,表明体重变化与蛋白尿的平行变化相关。这种关系不能完全由体重与经典心血管危险因素及肾功能之间的关联来解释。基于我们的数据,我们推测体重引起的血管炎症变化可能导致蛋白尿变化。