LDL Cholesterol and Cardiovascular Risk After Kidney Transplantation: Insights from a Global Registry

Background: Although cardiovascular disease (CVD) rates decline after kidney transplant (KT), CVD-related mortality remains higher than in the general population. The 2013 KDIGO workgroup recommended statins for all adult KT recipients but noted that higher doses lack proven safety. ACC/AHA do not address CKD, but their risk-based model supports moderate-to-high intensity statins for KT patients. Given these varied recommendations, we examined the link between post-KT LDL targets and CVD outcomes and mortality. Methods: An observational retrospective cohort study using the TriNetX Global network (148 health care organizations) included adults with kidney-only KT from Jan-2010 to Dec-2021 and on statins within 1 year. LDL was assessed 1–2 years post-KT. Sensitivity analysis was performed on three LDL thresholds ≤70, ≤100 and ≤130mg/dL based on the last value. Followup was censored on 05/15/2025. Propensity score matching (1:1) was performed using 43 variables at each threshold. The primary outcome for each threshold was major adverse cardiovascular events (MACE): myocardial infarction, heart failure, stroke, cardiac arrest, or death. Secondary outcomes for each threshold included mortality, MACE components and statin-related adverse events (AEs). Kaplan-Meier analysis and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were calculated using Cox models. Results: 18359 adults [mean age 55.8±21.1 years, 62.3% male, 48.4% White were included. Of 10752 (58.6%) had LDL data. Patients in each threshold LDL≤70, LDL≤100 and LDL≤130 were 1:1 matched with those above threshold. MACE occurrence was 28% (LDL≤70 ) vs 29.4% (LDL>70) (aHR 1.04; CI 0.94-1.16) and 24.6% (LDL≤100) vs 28.2% (LDL>100)(aHR 0.90; CI 0.80–1.01). At the threshold of ≤130 there was a significant MACE risk reduction, with 21.5% (LDL≤130) vs 27.6% (LDL>130) (aHR 0.78; 95% CI 0.65-0.95). Mortality and Statin-related AEs were no different at all three thresholds. Conclusion: Within the limitations of a 5-year follow-up, LDL thresholds of ≤70, ≤100 mg/dL and ≤130 were not associated with reduced mortality in KT patients. Further analysis based upon statin dosing may be necessary. Given the high rate of MACEs in the overall treated population (~25-30%), new biomarkers and therapeutic targets should be evaluated to improve cardiovascular-metabolic outcomes.