Abstract：
BACKGROUND: 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.
OBJECTIVE: The objective of the study was twofold: i) to investigate the association between all-cause mortality and eGFR changes over time; ii) to understand whether renal dysfunction mediates the effect of tryptophan metabolism on death risk.
METHODS: Prospective study with an average follow-up of 14.8 years.
METHODS: Research Hospital.
METHODS: The aggregate Gargano Mortality Study included 962 patients with type 2 diabetes who had at least three eGFR recordings and at least 1.5 years of follow-up.
METHODS: This was an observational study, with no intervention.
METHODS: Rate of all-cause mortality.
RESULTS: 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.
CONCLUSIONS: 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.
OBJECTIVE: The objective of the study was twofold: i) to investigate the association between all-cause mortality and eGFR changes over time; ii) to understand whether renal dysfunction mediates the effect of tryptophan metabolism on death risk.
METHODS: Prospective study with an average follow-up of 14.8 years.
METHODS: Research Hospital.
METHODS: The aggregate Gargano Mortality Study included 962 patients with type 2 diabetes who had at least three eGFR recordings and at least 1.5 years of follow-up.
METHODS: This was an observational study, with no intervention.
METHODS: Rate of all-cause mortality.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：肾小球滤过率（GFR）下降对2型糖尿病患者死亡风险的独立作用仅得到部分解决。
目的：该研究的目的是双重的：i）研究全因死亡率与eGFR随时间变化的相关性；ii）了解肾功能障碍是否介导色氨酸代谢对死亡风险的影响。
方法：前瞻性研究，平均随访14.8年。
方法：研究医院。
方法：Gargano总死亡率研究包括962名2型糖尿病患者，他们有至少3个eGFR记录和至少1.5年的随访。
方法：这是一项观察性研究，没有干预。
方法：全因死亡率。
结果：年龄和性别调整后的年事件死亡率为每100人年2.75例。eGFR的年下降速率中位数为每年每1.73m21.3ml/min（范围-3.7;7.8）。肾功能下降与死亡风险密切相关。血清犬尿氨酸与色氨酸比值（KTR）与eGFR下降和全因死亡率相关。因果中介分析显示，KTR和死亡率之间的24.3％的关联是由eGFR下降介导的。
结论：在2型糖尿病患者中，eGFR下降与全因死亡风险独立相关，并介导色氨酸代谢与死亡之间的显著关联。
目的：该研究的目的是双重的：i）研究全因死亡率与eGFR随时间变化的相关性；ii）了解肾功能障碍是否介导色氨酸代谢对死亡风险的影响。
方法：前瞻性研究，平均随访14.8年。
方法：研究医院。
方法：Gargano总死亡率研究包括962名2型糖尿病患者，他们有至少3个eGFR记录和至少1.5年的随访。
方法：这是一项观察性研究，没有干预。
方法：全因死亡率。
结果：年龄和性别调整后的年事件死亡率为每100人年2.75例。eGFR的年下降速率中位数为每年每1.73m21.3ml/min（范围-3.7;7.8）。肾功能下降与死亡风险密切相关。血清犬尿氨酸与色氨酸比值（KTR）与eGFR下降和全因死亡率相关。因果中介分析显示，KTR和死亡率之间的24.3％的关联是由eGFR下降介导的。
结论：在2型糖尿病患者中，eGFR下降与全因死亡风险独立相关，并介导色氨酸代谢与死亡之间的显著关联。
