Lamacchia Olga, Menzaghi Claudia, Copetti Massimiliano, Mastroianno Mario, Corsano Chiara, Prehn Cornelia, Adamski Jerzy, Fontana Andrea, Trischitta Vincenzo, De Cosmo Salvatore
Department of Medical and Surgical Sciences, Endocrinology Unit, University of Foggia, 71122 Foggia, Italy.
Research Unit of Diabetes and Endocrine Diseases, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy.
J Clin Endocrinol Metab. 2025 Apr 22;110(5):e1451-e1457. doi: 10.1210/clinem/dgae551.
The independent role of glomerular filtration rate (GFR) decline in shaping the risk of mortality in people with type 2 diabetes has only been partially addressed.
The objective of the study was 2-fold: (1) to investigate the association between all-cause mortality and eGFR changes over time; (2) to understand whether renal dysfunction mediates the effect of tryptophan metabolism on death risk.
Prospective study with an average follow-up of 14.8 years at a research hospital. The aggregate Gargano Mortality Study included 962 patients with type 2 diabetes who had at least 3 eGFR recordings and at least 1.5 years of follow-up. This was an observational study, with no interventions. Rate of all-cause mortality was measured.
Age- and sex-adjusted annual incident rate of mortality was 2.75 events per 100 person-years. The median annual rate of decline of eGFR was 1.3 mL/min per 1.73 m2 per year (range -3.7; 7.8). The decline of kidney function was strongly and independently associated with the risk of death. Serum kynurenine to tryptophan ratio (KTR) was associated with both eGFR decline and all-cause mortality. Causal mediation analysis showed that 24.3% of the association between KTR and mortality was mediated by eGFR decline.
In patients with type 2 diabetes, eGFR decline is independently associated with the risk of all-cause mortality and mediates a significant proportion of the association between tryptophan metabolism and death.
肾小球滤过率（GFR）下降在塑造2型糖尿病患者死亡风险方面的独立作用仅得到部分探讨。
本研究的目的有两个：（1）调查全因死亡率与估算肾小球滤过率（eGFR）随时间变化之间的关联；（2）了解肾功能不全是否介导色氨酸代谢对死亡风险的影响。
在一家研究医院进行的前瞻性研究，平均随访14.8年。加加诺总体死亡率研究纳入了962例2型糖尿病患者，这些患者至少有3次eGFR记录且至少有1.5年的随访期。这是一项观察性研究，无干预措施。测量全因死亡率。
年龄和性别调整后的年死亡率为每100人年2.75例。eGFR的年中位数下降率为每年1.3 mL/（min·1.73 m²）（范围为-3.7；7.8）。肾功能下降与死亡风险密切且独立相关。血清犬尿氨酸与色氨酸比值（KTR）与eGFR下降和全因死亡率均相关。因果中介分析表明，KTR与死亡率之间24.3%的关联是由eGFR下降介导的。
在2型糖尿病患者中，eGFR下降与全因死亡风险独立相关，并介导了色氨酸代谢与死亡之间相当一部分的关联。
