Department of Medicine, San Francisco VA Medical Center, San Francisco, California, USA.
JAMA. 2011 Apr 20;305(15):1545-52. doi: 10.1001/jama.2011.468. Epub 2011 Apr 11.
A triple-marker approach for chronic kidney disease (CKD) evaluation has not been well studied.
To evaluate whether combining creatinine, cystatin C, and urine albumin-to-creatinine ratio (ACR) would improve identification of risks associated with CKD compared with creatinine alone.
DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study involving 26,643 US adults enrolled in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study from January 2003 to June 2010. Participants were categorized into 8 groups defined by estimated glomerular filtration rate (GFR) determined by creatinine and by cystatin C of either <60 or ≥60 mL/min/1.73 m(2) and ACR of either <30 or ≥30 mg/g.
All-cause mortality and incident end-stage renal disease with median follow-up of 4.6 years.
Participants had a mean age of 65 years, 40% were black, and 54% were women. Of 26,643 participants, 1940 died and 177 developed end-stage renal disease. Among participants without CKD defined by creatinine, 24% did not have CKD by either ACR or cystatin C. Compared with those with CKD defined by creatinine alone, the hazard ratio for death in multivariable-adjusted models was 3.3 (95% confidence interval [CI], 2.0-5.6) for participants with CKD defined by creatinine and ACR; 3.2 (95% CI, 2.2-4.7) for those with CKD defined by creatinine and cystatin C, and 5.6 (95% CI, 3.9-8.2) for those with CKD defined by all biomarkers. Among participants without CKD defined by creatinine, 3863 (16%) had CKD detected by ACR or cystatin C. Compared with participants who did not have CKD by any measure, the HRs for mortality were 1.7 (95% CI, 1.4-1.9) for participants with CKD defined by ACR alone, 2.2 (95% CI, 1.9-2.7) for participants with CKD defined by cystatin C alone, and 3.0 (95% CI, 2.4-3.7) for participants with CKD defined by both measures. Risk of incident end-stage renal disease was higher among those with CKD defined by all markers (34.1 per 1000 person-years; 95% CI, 28.7-40.5 vs 0.33 per 1000 person-years; 95% CI, 0.05-2.3) for those with CKD defined by creatinine alone. The second highest end-stage renal disease rate was among persons missed by the creatinine measure but detected by both ACR and cystatin C (rate per 1000 person-years, 6.4; 95% CI, 3.6-11.3). Net reclassification improvement for death was 13.3% (P < .001) and for end-stage renal disease was 6.4% (P < .001) after adding estimated GFR cystatin C in fully adjusted models with estimated GFR creatinine and ACR.
Adding cystatin C to the combination of creatinine and ACR measures improved the predictive accuracy for all-cause mortality and end-stage renal disease.
尚未对慢性肾脏病（CKD）评估的三标志物方法进行充分研究。
评估与仅使用肌酐相比，将肌酐、胱抑素 C 和尿白蛋白与肌酐比值（ACR）相结合是否能提高与 CKD 相关的风险识别能力。
设计、地点和参与者：前瞻性队列研究，纳入了 2003 年 1 月至 2010 年 6 月期间参与 Reasons for Geographic and Racial Differences in Stroke（REGARDS）研究的 26643 名美国成年人。参与者根据肌酐和胱抑素 C 确定的估计肾小球滤过率（GFR）分为 8 组，分为<60 或≥60 mL/min/1.73 m²和 ACR 为<30 或≥30 mg/g。
全因死亡率和终末期肾病的发生率，中位随访时间为 4.6 年。
参与者的平均年龄为 65 岁，40%为黑人，54%为女性。在 26643 名参与者中，有 1940 人死亡，177 人发展为终末期肾病。在没有通过肌酐定义的 CKD 的参与者中，有 24%没有通过 ACR 或胱抑素 C 定义的 CKD。与仅通过肌酐定义的 CKD 相比，在多变量调整模型中，通过肌酐和 ACR 定义的 CKD 的死亡风险比为 3.3（95%置信区间[CI]，2.0-5.6）；通过肌酐和胱抑素 C 定义的 CKD 的风险比为 3.2（95% CI，2.2-4.7）；通过所有生物标志物定义的 CKD 的风险比为 5.6（95% CI，3.9-8.2）。在没有通过肌酐定义的 CKD 的参与者中，有 3863 人（16%）通过 ACR 或胱抑素 C 检测到 CKD。与任何方法都未患有 CKD 的参与者相比，死亡率的 HR 为：仅通过 ACR 定义的 CKD 为 1.7（95% CI，1.4-1.9）；仅通过胱抑素 C 定义的 CKD 为 2.2（95% CI，1.9-2.7）；同时通过两种方法定义的 CKD 为 3.0（95% CI，2.4-3.7）。通过所有标志物定义的 CKD 患者的终末期肾病发生率更高（每 1000 人年 34.1 例；95% CI，28.7-40.5 比每 1000 人年 0.33 例；95% CI，0.05-2.3）。肌酐测量漏诊但同时通过 ACR 和胱抑素 C 检测到的患者的终末期肾病发生率第二高（每 1000 人年 6.4 例；95% CI，3.6-11.3）。在使用肌酐和 ACR 进行充分调整的模型中添加估计的 GFR 胱抑素 C 后，死亡的净重新分类改善为 13.3%（P <.001），终末期肾病的净重新分类改善为 6.4%（P <.001）。
在肌酐和 ACR 联合检测的基础上添加胱抑素 C 可提高全因死亡率和终末期肾病的预测准确性。
