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Major adverse cardiovascular events and hyperuricemia as an effect-modifying factor in kidney transplant recipients
Elizabete Junk1,2, Lilian Tzivian2,3, Inese Folkmane2,4
1Department of Internal Diseases, St. Bonifatius Hospital Lingen, Lingen 49808, Germany.
Insights
High uric acid levels significantly increase the risk of major adverse cardiovascular events (MACEs) in kidney transplant recipients, particularly when combined with other risk factors like age and previous CV events.
Area of Science:
- Nephrology
- Cardiology
- Transplantation Medicine
Background:
- Major adverse cardiovascular events (MACEs) are a leading cause of death in kidney transplant (KT) recipients.
- Traditional and non-traditional cardiovascular (CV) risk factors contribute to MACEs in this population.
Purpose of the Study:
- To examine the association between KT-related CV risk factors and MACEs.
- To investigate the modifying effect of hyperuricemia (HU) on this association.
Main Methods:
- A cohort of 545 kidney transplant recipients transplanted between 2008-2019 was analyzed.
- Logistic regression models identified risk factors for MACEs.
- Patients were stratified by uric acid (UA) levels to assess HU's effect modification.
Main Results:
- MACEs occurred in 26.6% of KT recipients.
- Significant MACE predictors included prior CV events, left ventricular hypertrophy (LVH), HU treatment, and anemia.
- Very high UA levels (> 475 μmol/L) modified the association between risk factors and MACEs.
Conclusions:
- Very high UA levels act as an effect modifier for MACEs in kidney transplant recipients.
- The combination of high UA with age, prior CV events, LVH, and anemia elevates MACE risk.
Background:
Major adverse cardiovascular (CV) events (MACEs) are the primary cause of morbidity and mortality in kidney transplantation (KT) recipients. The risk for MACEs is impacted by an array of traditional and transplant-related non-traditional CV risk factors.
Aim:
To investigate the association between potential CV risk factors related to KT and MACEs, and their potential modification by hyperuricemia (HU).
Methods:
The relationship between CV risk factors related to KT and MACEs was examined in a cohort of 545 patients who underwent transplantation between 2008 and 2019. The mean age of patients at KT was 55.0 years ± 14.2 years (range 15.0-89.0 years). Univariate and multivariate logistic regression models were constructed to identify risk factors influencing MACEs. To explore the potential effect modification by uric acid (UA), patients were categorized into groups based on UA levels: (1) Low (< 356 μmol/L); (2) Normal (356-416 μmol/L); (3) High (416-475 μmol/L); and (4) Very high (> 475 μmol/L).
Results:
MACEs occurred in 145 of 545 (26.6%) KT recipients. The most prevalent comorbidities were hypertension (87%), dyslipidemia (78%), secondary hyperparathyroidism (68%), HU (63%) and anemia (33%). In the multivariate logistic regression model, the most significant factors associated with MACEs were previous CV events [odds ratio (OR) = 70.6, 95%CI: 24.9-200.1], left ventricular hypertrophy (LVH) (OR = 12.6, 95%CI: 2.7- 58.3), HU treatment (OR = 4.3, 95%CI: 2.4-7.6), and anemia (OR = 5.3, 95%CI: 2.9-9.8). Effect modification by the presence of HU revealed that independent factors associated with MACEs were age (OR = 1.03, 95%CI: 1.0-1.1), previous CV events (OR = 41.7, 95%CI: 13.6-127.6), LVH (OR = 15.3, 95%CI: 2.0-116.6), HU treatment (OR = 2.5, 95%CI: 1.3-4.6) and anemia (OR = 5.4, 95%CI: 2.8-10.5). Effect modification by UA levels dichotomized at 475 μmol/L (very high level of UA) revealed that HU treatment was not associated with MACEs in groups with or without very high UA levels.
Conclusion:
A very high level of UA was observed to act as an effect-modifying factor for MACEs, especially when combined with other risk factors such as age, previous CV events, LVH, and anemia.
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