https://orcid.org/0000-0002-9175-489X
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Olga Lamacchia, Claudia Menzaghi, Massimiliano Copetti, Mario Mastroianno, Chiara Corsano, Cornelia Prehn, Jerzy Adamski, Andrea Fontana, Vincenzo Trischitta, Salvatore De Cosmo, GFR Decline Predicts Total Mortality and Mediates the Effect of Tryptophan Metabolism on Death Risk in Type 2 Diabetes, The Journal of Clinical Endocrinology & Metabolism, Volume 110, Issue 5, May 2025, Pages e1451–e1457, https://doi.org/10.1210/clinem/dgae551
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Abstract
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.
