Garofolo Monia, Penno Giuseppe, Solini Anna, Orsi Emanuela, Vitale Martina, Resi Veronica, Bonora Enzo, Fondelli Cecilia, Trevisan Roberto, Vedovato Monica, Nicolucci Antonio, Pugliese Giuseppe
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Department of Surgical, Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy.
Diabetes Metab Res Rev. 2025 Jul;41(5):e70061. doi: 10.1002/dmrr.70061.
To investigate the independent association of albuminuria within the normoalbuminuric range with all-cause mortality in normoalbuminuric people with type 2 diabetes with and without chronic kidney disease (CKD).
This observational, prospective, multicentre, cohort study enroled 15,773 individuals with type 2 diabetes in 2006-2008. At baseline, albumin excretion rate (AER) and estimated glomerular filtration rate (eGFR) were assessed together with cardiometabolic risk profile, treatments, complications, and comorbidities. All-cause mortality was verified on 31 October 2015.
Of the 15,656 participants (99.3%) with valid information on vital status, 11,460 (71.2%) were normoalbuminuric, 9984 (87.1%) without and 1476 (12.9%) with CKD. Normoalbuminuric individuals were stratified into three (< 5, 5-15, and > 15 mg·day) or two (< 10 and 10-29 mg·day) AER subcategories. When adjusting for age, sex, eGFR, prior cardiovascular disease, cardiovascular risk factors, and treatments, mortality risk was higher in participants with AER 10-29 versus < 10 mg·day (hazard ratio, 1.120 [95% confidence interval, 1.028-1.221], p = 0.009) and 15-29 versus < 5 mg·day (1.243 [1.099-1.406], p < 0.0001). When stratifying by CKD status, the adjusted risk remained significantly increased only for AER 15-29 versus < 5 mg/24 h in individuals with (1.404 [1.111-1.774], p = 0.005) and, to a lesser extent, without (1.167 [1.009-1.350], p = 0.038) CKD. A non-linear association was observed between AER as Log2 transformed continuous variable and mortality.
For the same level of kidney function, higher AER within the normoalbuminuric range was independently associated with all-cause mortality, thus supporting to the use of albuminuria-lowering drugs in people with type 2 diabetes and mildly elevated albuminuria.
ClinicalTrials.gov, NCT00715481, retrospectively registered 15 July, 2008.
研究正常白蛋白尿范围内的蛋白尿与伴有或不伴有慢性肾脏病（CKD）的2型糖尿病正常白蛋白尿患者全因死亡率之间的独立关联。
这项观察性、前瞻性、多中心队列研究在2006 - 2008年纳入了15773例2型糖尿病患者。在基线时，评估了白蛋白排泄率（AER）和估计肾小球滤过率（eGFR），同时评估了心血管代谢风险状况、治疗、并发症和合并症。于2015年10月31日核实全因死亡率。
在15656名（99.3%）有有效生命状态信息的参与者中，11460名（71.2%）为正常白蛋白尿，其中9984名（87.1%）无CKD，1476名（12.9%）有CKD。正常白蛋白尿个体被分为三个（<5、5 - 15和>15mg·天）或两个（<10和10 - 29mg·天）AER亚组。在调整年龄、性别、eGFR、既往心血管疾病、心血管危险因素和治疗因素后，AER为10 - 29mg·天的参与者与<10mg·天的参与者相比，死亡风险更高（风险比，1.120[95%置信区间，1.028 - 1.221]，p = 0.009），AER为15 - 29mg·天的参与者与<5mg·天的参与者相比也是如此（1.243[1.099 - 1.406]，p < 0.0001）。按CKD状态分层时，仅在有CKD的个体中，AER为15 - 29mg/24小时与<5mg/24小时相比，调整后的风险仍显著增加（1.404[1.111 - 1.774]，p = 0.005），在无CKD的个体中增加程度较小（1.167[1.009 - 1.350]，p = 0.038）。观察到作为Log2转换后的连续变量的AER与死亡率之间存在非线性关联。
对于相同水平的肾功能，正常白蛋白尿范围内较高的AER与全因死亡率独立相关，因此支持在2型糖尿病和轻度白蛋白尿升高的患者中使用降低蛋白尿的药物。
ClinicalTrials.gov，NCT00715481，于2008年7月15日进行回顾性注册。
