Impact of different A1c targets on cardiovascular outcomes in diabetic kidney transplant recipients: A global cohort analysis

BACKGROUND: Optimal glycemic targets for diabetic kidney transplant recipients (KTRs) remain uncertain, particularly regarding cardiovascular outcomes. MATERIALS AND METHODS: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network, including adult KTRs with type 2 diabetes transplanted from 2010 - 2021. Patients with simultaneous kidney-pancreas or pancreas-alone transplants were excluded. HbA1c measured 1 - 2 years post transplant was categorized as ≤ 7.5% or > 7.5%. Propensity score matching (1 : 1) balanced demographics, comorbidities, laboratory values, immunosuppression, and medications. The primary outcome was major adverse cardiovascular events (MACE: myocardial infarction, stroke, heart failure, cardiac arrest, or death); secondary outcomes included individual components of MACE and graft failure. RESULTS: The final matched cohort included 5,850 patients (2,925 per group). Over median follow-up of 4.2 years, MACE occurred in 33.4% of patients with HbA1c ≤ 7.5 vs. 39.1% with > 7.5% (adjusted hazard ratio (aHR) 0.88, 95% CI 0.78 - 0.98). Mortality was lower in the ≤ 7.5% group (19.6 vs. 23.7%; aHR 0.85, 95% CI 0.76 - 0.95). No significant differences were observed in graft failure, myocardial infarction, heart failure, or stroke. Sensitivity analyses demonstrated lowest MACE and mortality risk at HbA1c 7.0 - 8.0%, with attenuation at ≤ 7.0% and loss of significance at ≤ 6.5%. Cardiovascular benefit was most pronounced in patients < 65 years and those with favorable lipid profiles. CONCLUSION: In this global retrospective observational study, moderate glycemic control (HbA1c ~ 7 - 8% measured 1 - 2 years post transplant) was associated with lower cardiovascular events and mortality in type 2 diabetic KTRs. These findings support individualized targets aimed at avoiding both poor control and overly intensive lowering.