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Urea levels and cardiovascular disease in patients with chronic kidney disease
Solène M Laville1,2, Aymeric Couturier3, Oriane Lambert4
1Department of Clinical Pharmacology, Amiens University Hospital, Amiens, France.
Insights
Elevated serum urea in chronic kidney disease (CKD) patients predicts cardiovascular events and death before renal replacement therapy (RRT). Higher urea levels correlate with increased risks, independent of other risk factors.
Area of Science:
- Nephrology
- Cardiology
- Clinical Research
Background:
- Elevated serum urea is common in moderate-to-advanced chronic kidney disease (CKD).
- Urea acts as a uremic toxin, particularly impacting cardiovascular health.
- The association between serum urea levels and adverse cardiovascular outcomes before renal replacement therapy (RRT) requires further investigation.
Purpose of the Study:
- To determine if serum urea levels are associated with adverse cardiovascular events.
- To assess the relationship between serum urea levels and mortality before RRT in CKD patients.
- To investigate urea's predictive value for cardiovascular outcomes beyond established risk factors.
Main Methods:
- Prospective cohort study (CKD-REIN) of 2507 CKD outpatients not on dialysis.
- Patients stratified into three baseline serum urea groups (T1 < 10.5, T2: 10.5–15.1, T3 ≥ 15.1 mmol/L).
- Cox proportional hazard models used to estimate hazard ratios (HRs) for cardiovascular events and all-cause mortality, adjusted for comorbidities and medications.
Main Results:
- Patients in the highest urea group (T3) showed a significantly higher risk of atheromatous and non-atheromatous cardiovascular events (HR: 1.93 [1.39–2.69]) compared to the lowest group (T1).
- Adjusted HRs for death before RRT were elevated for both intermediate (T2: 1.31 [0.97–1.76]) and high (T3: 1.73 [1.22–2.45]) urea groups.
- Over half the cohort (54%) had a prior history of cardiovascular disease.
Conclusions:
- Serum urea levels are a significant predictor of cardiovascular outcomes in CKD patients.
- Urea's predictive power for cardiovascular events and mortality extends beyond traditional risk factors, including estimated glomerular filtration rate (eGFR).
- These findings highlight the importance of monitoring and potentially managing serum urea levels in CKD management.
Background:
Elevated serum urea levels are common in moderate-to-advanced CKD. Several studies have shown that urea is a direct and indirect uremic toxin, especially with regard to cardiovascular disease. We sought to determine whether serum urea levels are associated with adverse cardiovascular events and death before renal replacement therapy (RRT) in patients with CKD.
Methods:
CKD-REIN is a prospective cohort of CKD nephrology outpatients not receiving maintenance dialysis. The 2507 patients included in the analysis were divided into three groups according to the baseline serum urea level (T1 < 10.5, T2:10.5 to 15.1, and T3 ≥ 15.1 mmol/L). Cox proportional hazard models were used to estimate hazard ratios (HRs) for first atheromatous or nonatheromatous cardiovascular (CV) events, and all-cause mortality before RRT. The models were adjusted for baseline comorbidities, laboratory data, and medications.
Findings:
Of the 2507 included patients (median [interquartile range (IQR)] age: 69[61-77]; mean (standard deviation) eGFR 33.5(11.6) mL/min/1.73 m²), 54% had a history of cardiovascular disease. After multiple adjustments for cardiovascular risk factors (including eGFR), patients in T3 had a higher risk of atheromatous and nonatheromatous cardiovascular events than patient in T1 (n events = 451, HR[95%CI]: 1.93[1.39-2.69]). The adjusted HRs for death before RRT (n events = 407) were 1.31[0.97; 1.76] and 1.73[1.22; 2.45] for patients T2 and those in T3, respectively.
Interpretation:
Our data suggested that urea is a predictor of cardiovascular outcomes beyond CV risk factors including eGFR.
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