Monocyte IL-1β predicts adverse cardiovascular events and associates with coronary microvascular dysfunction in...

Cardiovascular disease remains the leading cause of death after kidney transplantation. Coronary microvascular dysfunction (CMD) is common in kidney transplant recipients (KTRs), prognostically informative for cardiovascular events, and tightly related to inflammation. We aimed to test whether pretransplant monocytic expression of pyroptosis-related genes (IL-1β, GSDMD, Caspase-1, and NLRP3) independently predicts long-term mortality and major adverse cardiovascular events (MACE) in KTRs, and to evaluate its associations with CMD.

We enrolled 305 KTRs. Monocytes were isolated preoperatively and qPCR quantified the four genes (normalized to GAPDH). MACE included death, myocardial infarction, stroke, and heart failure. Multivariable Cox regression was used to adjust for confounders associated with prognosis. CMD was evaluated using coronary flow reserve (CFR) in 41 KTRs and serum syndecan-1 levels (an endothelial injury marker) in 88 KTRs.

Over a median 4.0 years, 62/305 (20.3%) had MACE. IL-1β expression was higher in those with events. In Cox models with IL-1β entered as a standardized continuous variable (per SD), IL-1β independently predicted death (adjusted HR 1.530, 95%CI 1.165-2.009) and MACE (adjusted HR 1.622, 95%CI 1.283-2.052). When modeled categorically as tertiles, the highest vs. lowest IL-1β tertile conferred greater risk (death, adjusted HR 3.771, 95%CI 1.516-9.384; MACE, adjusted HR 4.398, 95%CI 2.003-9.654). IL-1β correlated inversely with CFR (R = -0.40, P = 0.009) and positively with syndecan-1 (R = 0.47, P < 0.001). Other genes showed weaker or nonsignificant associations.

IL-1β is a robust, independent predictor of death and MACE in KTRs. Its associations with impaired CFR and elevated syndecan-1 support a mechanistic link to CMD.