Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Lancet Diabetes Endocrinol. 2017 Sep;5(9):718-728. doi: 10.1016/S2213-8587(17)30183-3. Epub 2017 Jul 14.
Some evidence suggests that chronic kidney disease is a risk factor for lower-extremity peripheral artery disease. We aimed to quantify the independent and joint associations of two measures of chronic kidney disease (estimated glomerular filtration rate [eGFR] and albuminuria) with the incidence of peripheral artery disease.
In this collaborative meta-analysis of international cohorts included in the Chronic Kidney Disease Prognosis Consortium (baseline measurements obtained between 1972 and 2014) with baseline measurements of eGFR and albuminuria, at least 1000 participants (this criterion not applied to cohorts exclusively enrolling patients with chronic kidney disease), and at least 50 peripheral artery disease events, we analysed adult participants without peripheral artery disease at baseline at the individual patient level with Cox proportional hazards models to quantify associations of creatinine-based eGFR, urine albumin-to-creatinine ratio (ACR), and dipstick proteinuria with the incidence of peripheral artery disease (including hospitalisation with a diagnosis of peripheral artery disease, intermittent claudication, leg revascularisation, and leg amputation). We assessed discrimination improvement through c-statistics.
We analysed 817 084 individuals without a history of peripheral artery disease at baseline from 21 cohorts. 18 261 cases of peripheral artery disease were recorded during follow-up across cohorts (median follow-up was 7·4 years [IQR 5·7-8·9], range 2·0-15·8 years across cohorts). Both chronic kidney disease measures were independently associated with the incidence of peripheral artery disease. Compared with an eGFR of 95 mL/min per 1·73 m, adjusted hazard ratios (HRs) for incident study-specific peripheral artery disease was 1·22 (95% CI 1·14-1·30) at an eGFR of 45 mL/min per 1·73 m and 2·06 (1·70-2·48) at an eGFR of 15 mL/min per 1·73 m. Compared with an ACR of 5 mg/g, the adjusted HR for incident study-specific peripheral artery disease was 1·50 (1·41-1·59) at an ACR of 30 mg/g and 2·28 (2·12-2·44) at an ACR of 300 mg/g. The adjusted HR at an ACR of 300 mg/g versus 5 mg/g was 3·68 (95% CI 3·00-4·52) for leg amputation. eGFR and albuminuria contributed multiplicatively (eg, adjusted HR 5·76 [4·90-6·77] for incident peripheral artery disease and 10·61 [5·70-19·77] for amputation in eGFR <30 mL/min per 1·73 m plus ACR ≥300 mg/g or dipstick proteinuria 2+ or higher vs eGFR ≥90 mL/min per 1·73 m plus ACR <10 mg/g or dipstick proteinuria negative). Both eGFR and ACR significantly improved peripheral artery disease risk discrimination beyond traditional predictors, with a substantial improvement prediction of amputation with ACR (difference in c-statistic 0·058, 95% CI 0·045-0·070). Patterns were consistent across clinical subgroups.
Even mild-to-moderate chronic kidney disease conferred increased risk of incident peripheral artery disease, with a strong association between albuminuria and amputation. Clinical attention should be paid to the development of peripheral artery disease symptoms and signs in people with any stage of chronic kidney disease.
American Heart Association, US National Kidney Foundation, and US National Institute of Diabetes and Digestive and Kidney Diseases.
一些证据表明慢性肾脏病是下肢外周动脉疾病的一个危险因素。我们旨在定量评估两种慢性肾脏病衡量指标（估算肾小球滤过率[eGFR]和白蛋白尿）与外周动脉疾病发病之间的独立和联合关联。
在这项由慢性肾脏病预后联盟（Chronic Kidney Disease Prognosis Consortium）纳入的国际队列的合作荟萃分析中（基线测量值在 1972 年至 2014 年间获得），至少有 1000 名参与者（这一标准不适用于专门招募慢性肾脏病患者的队列），并且至少有 50 例外周动脉疾病事件，我们使用 Cox 比例风险模型对个体患者水平上无基线外周动脉疾病的成年参与者进行了分析，以量化肌酐 eGFR、尿白蛋白与肌酐比值（ACR）和尿蛋白试纸检测与外周动脉疾病发病之间的关联（包括外周动脉疾病的诊断性住院、间歇性跛行、下肢血运重建和下肢截肢）。我们通过 C 统计量评估了判别改善情况。
我们分析了来自 21 个队列的 817084 名基线时无外周动脉疾病病史的个体。在整个队列的随访期间记录了 18261 例外周动脉疾病病例（中位随访时间为 7.4 年[IQR 5.7-8.9]，各队列的范围为 2.0-15.8 年）。两种慢性肾脏病指标都与外周动脉疾病的发病独立相关。与 eGFR 为 95 mL/min/1.73 m 相比，在 eGFR 为 45 mL/min/1.73 m 时，研究特异性外周动脉疾病的调整后的危险比（HR）为 1.22（95%CI 1.14-1.30），在 eGFR 为 15 mL/min/1.73 m 时为 2.06（1.70-2.48）。与 ACR 为 5 mg/g 相比，在 ACR 为 30 mg/g 时，研究特异性外周动脉疾病的调整后 HR 为 1.50（1.41-1.59），在 ACR 为 300 mg/g 时为 2.28（2.12-2.44）。ACR 为 300 mg/g 与 5 mg/g 相比，下肢截肢的调整后 HR 为 3.68（95%CI 3.00-4.52）。eGFR 和白蛋白尿呈乘法关系（例如，在 eGFR <30 mL/min/1.73 m 加 ACR ≥300 mg/g 或尿蛋白试纸 2+或更高 vs eGFR ≥90 mL/min/1.73 m 加 ACR <10 mg/g 或尿蛋白试纸阴性的情况下，发生外周动脉疾病的调整后 HR 为 5.76[4.90-6.77]，发生截肢的 HR 为 10.61[5.70-19.77]）。eGFR 和 ACR 都显著提高了外周动脉疾病风险的判别能力，并且 ACR 对截肢的预测能力有显著提高（差异在 C 统计量中为 0.058，95%CI 0.045-0.070）。在各临床亚组中均存在相似的模式。
即使是轻度至中度慢性肾脏病也会增加外周动脉疾病发病的风险，白蛋白尿与截肢之间存在强烈关联。临床医生应注意慢性肾脏病任何阶段患者外周动脉疾病症状和体征的发展。
美国心脏协会、美国国家肾脏基金会和美国国家糖尿病、消化和肾脏疾病研究所。
