Steno Diabetes Center Copenhagen, Gentofte, Denmark
Diabetes Research Unit Cymru, Swansea University Medical School, Swansea, U.K.
Diabetes Care. 2021 Apr;44(4):1020-1026. doi: 10.2337/dc20-1622. Epub 2021 Jan 27.
A post hoc analysis to investigate the association between 1-year changes in albuminuria and subsequent risk of cardiovascular and renal events.
LEADER was a randomized trial of liraglutide up to 1.8 mg/day versus placebo added to standard care for 3.5-5 years in 9,340 participants with type 2 diabetes and high cardiovascular risk. We calculated change in urinary albumin-to-creatinine ratio (UACR) from baseline to 1 year in participants with >30% reduction ( = 2,928), 30-0% reduction ( = 1,218), or any increase in UACR ( = 4,124), irrespective of treatment. Using Cox regression, risks of major adverse cardiovascular events (MACE) and a composite nephropathy outcome (from 1 year to end of trial in subgroups by baseline UACR [<30 mg/g, 30-300 mg/g, or ≥300 mg/g]) were assessed. The analysis was adjusted for treatment allocation alone as a fixed factor and for baseline variables associated with cardiovascular and renal outcomes.
For MACE, hazard ratios (HRs) for those with >30% and 30-0% UACR reduction were 0.82 (95% CI 0.71, 0.94; = 0.006) and 0.99 (0.82, 1.19; = 0.912), respectively, compared with any increase in UACR (reference). For the composite nephropathy outcome, respective HRs were 0.67 (0.49, 0.93; = 0.02) and 0.97 (0.66, 1.43; = 0.881). Results were independent of baseline UACR and consistent in both treatment groups. After adjustment, HRs were significant and consistent in >30% reduction subgroups with baseline micro- or macroalbuminuria.
A reduction in albuminuria during the 1st year was associated with fewer cardiovascular and renal outcomes, independent of treatment. Albuminuria monitoring remains an important part of diabetes care, with great unused potential.
事后分析旨在研究蛋白尿的 1 年变化与随后心血管和肾脏事件风险之间的关联。
LEADER 是一项为期 3.5-5 年的随机试验，9340 例 2 型糖尿病和高心血管风险患者接受利拉鲁肽（最高 1.8mg/天）或安慰剂联合标准治疗。我们计算了基线至 1 年时尿白蛋白与肌酐比值（UACR）变化的参与者>30%（=2928），30-0%（=1218）或任何 UACR 增加（=4124），不论治疗情况如何。使用 Cox 回归，评估主要不良心血管事件（MACE）和复合肾病结局（根据基线 UACR[<30mg/g，30-300mg/g 或≥300mg/g]的亚组从 1 年到试验结束的风险）。该分析仅调整了治疗分配作为固定因素，并调整了与心血管和肾脏结局相关的基线变量。
对于 MACE，与 UACR 增加相比，>30%和 30-0%UACR 降低的患者的危险比（HR）分别为 0.82（95%CI 0.71，0.94；=0.006）和 0.99（0.82，1.19；=0.912）。对于复合肾病结局，相应的 HR 分别为 0.67（0.49，0.93；=0.02）和 0.97（0.66，1.43；=0.881）。结果独立于基线 UACR，在两组治疗中均一致。调整后，在基线存在微量白蛋白尿或大量白蛋白尿的>30%降低亚组中，HR 具有统计学意义且一致。
第 1 年蛋白尿减少与心血管和肾脏结局减少相关，与治疗无关。蛋白尿监测仍然是糖尿病护理的重要组成部分，具有巨大的未开发潜力。
