{Reference Type}: Journal Article
{Title}: GFR decline predicts total mortality and mediates the effect of tryptophan metabolism on death risk in type 2 diabetes.
{Author}: Lamacchia O;Menzaghi C;Copetti M;Mastroianno M;Corsano C;Prehn C;Adamski J;Fontana A;Trischitta V;De Cosmo S;
{Journal}: J Clin Endocrinol Metab
{Volume}: 0
{Issue}: 0
{Year}: 2024 Aug 13
{Factor}: 6.134
{DOI}: 10.1210/clinem/dgae551
{Abstract}: <B>BACKGROUND: </B>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.<BR><B>OBJECTIVE: </B>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.<BR><B>METHODS: </B>Prospective study with an average follow-up of 14.8 years.<BR><B>METHODS: </B>Research Hospital.<BR><B>METHODS: </B>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.<BR><B>METHODS: </B>This was an observational study, with no intervention.<BR><B>METHODS: </B>Rate of all-cause mortality.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.