Urea levels and cardiovascular disease in patients with chronic kidney disease

Abstract

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.

Ketoanalogues Supplemental Low Protein Diet Safely Decreases Short-Term Risk of Dialysis among CKD Stage 4 Patients

“…Besides, regarding safety issues, previous studies have proven that, if the daily calorie intake is sufficient, sVLPDs or sLPDs in CKD patients could be safe, and even had some metabolic benefits, namely less hyperphosphatemia, less hyperparathyroidism, lower blood pressure, and gut microbiota modulation, which may additionally contribute to long-term cardiovascular protective effect and patient survival. One previous cohort study demonstrated that serum urea level is associated with CV outcomes in CKD patients, and further suggested a reduction of urea by nutritional therapy may thus be beneficial in reducing CV risks [ 33 ]. Actually, in this study, if we combined all common adverse events in CKD patients, including ESKD requiring dialysis, MACCEs, and all-cause mortality, into a composite outcome, patients continuing sLPDs would exhibit significantly lower risks of the composite outcomes.…”

Uremic Toxins and Cardiovascular Risk in Chronic Kidney Disease: What Have We Learned Recently beyond the Past Findings?

“…According to the KDIGO [25] and the Cardiovascular Stroke Endpoint Definitions for Clinical Trials [26], ATH CVDs include stroke or MI (whether fatal or not) and hospitalization for silent ischemia, unstable angina, transient ischemic attacks, intrastent thrombosis, peripheral artery disease (PAD), percutaneous coronary interventions or coronary artery bypass grafts, vascular surgery, amputation, and revascularization for coronary artery disease (CAD) or PAD. Furthermore, PAD can be defined as a history of amputation, angioplasty, or lower limb bypass prompted by ATH distal ischemic lesions [8,27].…”

“…Non-ATH CVD encompasses other types of CVD, including sudden cardiac death or death from heart failure (without a history of CAD), hospitalization for heart failure (again with no history of CAD), cardiac fibrosis, atrial fibrillation or other arrhythmia disorders, diastolic dysfunction, arterial stiffness, cardiomyocytes hypertrophy, vascular calcification, or valvular heart disease [8,27,32]. Prior cohorts concluded that the prevalence of heart failure increased markedly with CKD progression and affected 65 to 70% of patients with end-stage renal disease (ESRD) [33].…”

Liquid Crystal Droplet-Based Biosensors: Promising for Point-of-Care Testing

“…Urea serves as a crucial biomarker for the detection and clinical evaluation of urological illnesses [ 191 , 192 ]. Human urine typically has urea concentrations between 155 and 390 mM.…”