George Institute for Global Health, University of New South Wales, Newtown, New South Wales, Australia.
George Institute for Global Health, University of New South Wales, Newtown, New South Wales, Australia; Department of Epidemiology and Biostatistics, School of Public Health, The George Institute for Global Health, Imperial College London, London.
Am J Kidney Dis. 2021 Sep;78(3):350-360.e1. doi: 10.1053/j.ajkd.2021.02.335. Epub 2021 Apr 23.
RATIONALE & OBJECTIVE: Changes in urinary albumin-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) have been used separately as alternative kidney disease outcomes in randomized trials. We tested the hypothesis that combined changes in UACR and eGFR predict advanced kidney disease better than either alone. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: 91,319 primary care patients assembled from the Clinical Practice Research Datalink in the United Kingdom between 2000 and 2015. EXPOSURES: Changes in UACR and eGFR (categorized as ≥30% increase, stable, or ≥30% decrease), alone and in combination, over a 3-year period. OUTCOMES: The primary outcome was advanced CKD (sustained eGFR <30 mL/min/1.73 m); secondary outcomes included kidney failure, cardiovascular disease, and all-cause mortality. ANALYTICAL APPROACH: Multivariable Cox regression with bias from missing values assessed using multiple imputation; discrimination statistics compared across exposure groups. RESULTS: 91,319 individuals were studied, with a mean eGFR of 72.6 mL/min/1.73 m and median UACR of 9.7 mg/g; 70,957 (77.7%) had diabetes. During a median follow-up of 2.9 years, 2,541 people progressed to advanced CKD. Compared with stable values, hazard ratios for a ≥30% increase in UACR and ≥30% decrease in eGFR were 1.78 (95% CI, 1.59-1.98) and 7.53 (95% CI, 6.70-8.45), respectively, for the outcome of advanced CKD. Compared with stable values of both, the hazard ratio for the combination of an increase in UACR and a decrease in eGFR was 15.15 (95% CI, 12.43-18.46) for the outcome of advanced CKD. The combination of changes in UACR and eGFR predicted kidney outcomes better than either alone. LIMITATIONS: Selection bias, relatively small proportion of individuals without diabetes, and very few kidney failure events. CONCLUSIONS: In a large-scale general population, the combination of an increase in UACR and a decrease in eGFR was strongly associated with the risk of advanced CKD. Further assessment of combined changes in UACR and eGFR as an alternative outcome for kidney failure in trials of CKD progression is warranted.
背景与目的：尿白蛋白肌酐比值（UACR）和估算肾小球滤过率（eGFR）的变化已分别被用作随机试验中的替代肾脏疾病结局。我们检验了以下假设，即 UACR 和 eGFR 的联合变化预测晚期肾脏疾病的效果优于单独使用其中任何一个指标。
研究设计：观察性队列研究。
设置与参与者：2000 年至 2015 年间，从英国临床实践研究数据链中汇集了 91319 名初级保健患者。
暴露因素：3 年内 UACR 和 eGFR（分为≥30%增加、稳定或≥30%减少）的单独和联合变化。
结局：主要结局为晚期 CKD（持续 eGFR＜30 mL/min/1.73 m）；次要结局包括肾衰竭、心血管疾病和全因死亡率。
分析方法：使用多重插补法评估缺失值偏倚的多变量 Cox 回归；比较暴露组之间的判别统计量。
结果：研究了 91319 名个体，平均 eGFR 为 72.6 mL/min/1.73 m，中位数 UACR 为 9.7 mg/g；70957 人（77.7%）患有糖尿病。在中位随访 2.9 年后，2541 人进展为晚期 CKD。与稳定值相比，UACR 增加≥30%和 eGFR 减少≥30%的危险比分别为 1.78（95%CI，1.59-1.98）和 7.53（95%CI，6.70-8.45），用于晚期 CKD 的结局。与两者的稳定值相比，UACR 升高和 eGFR 降低的组合对晚期 CKD 的结局的危险比为 15.15（95%CI，12.43-18.46）。UACR 和 eGFR 变化的组合比单独使用任何一个指标更能预测肾脏结局。
局限性：选择偏倚、无糖尿病个体的比例相对较小、肾衰竭事件非常少。
结论：在大规模的一般人群中，UACR 升高和 eGFR 降低的联合与晚期 CKD 风险密切相关。进一步评估 UACR 和 eGFR 的联合变化作为 CKD 进展试验中肾衰竭的替代结局是合理的。
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