Cardiovascular disease in chronic kidney disease

Abstract

Individuals with chronic kidney disease (CKD) exhibit an increased risk for the development of cardiovascular disease (CVD) with its manifestations coronary artery disease, stroke, heart failure, arrhythmias, and sudden cardiac death. The presence of both, CVD and CKD has a major impact on the prognosis of patients. This association likely reflects the involvement of several pathophysiological mechanisms, including shared risk factors (e.g. diabetes and hypertension), as well as other factors such as inflammation, anaemia, volume overload, and the presence of uraemic toxins. Identifying and characterizing CKD is crucial for appropriate CVD risk prediction. Mitigating CVD risk in patients with CKD mandates a multidisciplinary approach involving cardiologists, nephrologists, and other health care professionals. The present State-of-the-Art Review addresses the current understanding on the pathophysiological link between CVD and CKD, clinical implications and challenges in the treatment of these patients.

Keywords: CV risk; Cardiovascular disease; Chronic kidney disease; GLP-1 receptor agonists; Non-steroidal MRAs; SGLT2 inhibitors.

Graphical Abstract

Figure 1

Current chronic kidney disease nomenclature used by KDIGO. KDIGO staging system for chronic kidney disease based on categories of glomerular filtration rate and urinary albumin creatinine ratio. The colours represent the risk of developing a need for dialysis or other relevant outcomes including cardiovascular disease. Green indicates low risk (and represents no chronic kidney disease if there is no structural or histological evidence of kidney disease). Compared with low risk (estimated at 0.04/1000 patient-years), yellow indicates chronic kidney disease with moderately increased risk (at least ∼5-fold), orange indicates chronic kidney disease with high risk (at least ∼20-fold), and red indicates chronic kidney disease with very high risk (at least ∼150-fold). From.

Figure 2

Adjusted hazard ratios and 95% CIs (shaded areas or whisker plots) of cardiovascular mortality (top row), coronary heart disease (second row), stroke (third row), and heart failure (bottom row) according to estimated glomerular filtration rate (left column) and albumin-to-creatinine ratio (right column) in the combined general population and high-risk cohorts. The reference is estimated glomerular filtration rate 95 mL/min/1.73 m² and albumin-to-creatinine ratio 5 mg/g (diamond). Dots represent statistical significance (P < .05). *Adjustments were for age, sex, race/ethnicity, smoking, systolic blood pressure, antihypertensive drugs, diabetes, total and high-density lipoprotein cholesterol concentrations, and albuminuria (albumin-to-creatinine ratio or dipstick) or estimated glomerular filtration rate, as appropriate. In the analyses of estimated glomerular filtration rate, there were 629 776 participants for cardiovascular mortality, 144 874 for coronary heart disease, 137 658 for stroke, and 105 127 for heart failure. In the analyses of albumin-to-creatinine ratio, there were 120 148 participants for cardiovascular mortality, 91 185 for coronary heart disease, 82 646 for stroke, and 55 855 for heart failure. Figure from Matsushita et al.

Figure 3

Organ cross talk between the kidney and the cardiovascular system in chronic kidney disease. Various mediators and mechanisms contribute to the development and progression of cardiovascular disease in patients with chronic kidney disease and a complex interaction of factors characterizes the multifaceted organ cross talk between the CV system and the kidney in the setting of chronic kidney disease. AGE, advanced glycation end products; PTM, posttranslational modification.

Figure 4

Clinical approach for the management of cardiovascular disease in patients with chronic kidney disease not on haemodialysis. A, All patients with cardiovascular disease need screening for the presence of chronic kidney disease by measurement of estimated glomerular filtration rate (eGFR) as well as urine albumin-to-creatinine ratio (UACR) assessment in the spot urine. Patients with both cardiovascular disease and chronic kidney disease benefit from standard treatment with a statin, RAS inhibition (angiotensin-converting enzyme inhibitor or angiotensin-II receptor blocker) as well as a sodium–glucose co-transporter-2 inhibitor on top of stringent blood pressure control with a systolic blood pressure < 130 mmHg. In addition, depending on the cardiovascular disease manifestation (coronary artery disease, heart failure with reduced ejection fraction (HFrEF), heart failure with mildly reduced ejection fraction/preserved ejection fraction (HFmrEF/HFpEF), or atrial fibrillation, additional specific therapies need to be implemented). B, All patients with cardiovascular disease and type 2 diabetes need screening for the presence of chronic kidney disease by measurement of eGFR as well as UACR assessment in the spot urine. Patients with cardiovascular disease, type 2 diabetes and chronic kidney disease benefit from standard treatment with a statin, semaglutide, RAS inhibition (angiotensin-converting enzyme inhibitor or angiotensin-II receptor blocker) as well as an sodium–glucose cotransporter 2 inhibitor on top of stringent blood pressure control (systolic blood pressure < 130 mmHg). In addition, depending on the cardiovascular disease manifestation (chronic kidney disease, HFrEF, HFmrEF/HFpEF, or atrial fibrillation, additional specific therapies need to be implemented. Afib, atrial fibrillation; ASA, acetylsalicylic acid; B-blocker, beta-blocker; MRA, mineralocorticoid-receptor antagonist.

Figure 5

Renal-based approach to initiation and titrating of multilevel guideline-directed medical therapy. Proposed flowchart for titrating guideline-directed medical therapy in the setting of chronic kidney disease. During titration the lower threshold of blood pressure should be individualized based on the presence of activity limiting hypotension rather than pure blood pressure values itself. ACE-I, angiotensin-converting enzyme inhibitor; ARNI, angiotensin receptor–neprilysin inhibitor; AV, atrioventricular; BP, blood pressure; Creat, creatinine; ECG, electrocardiogram; eGFR, estimated glomerular filtration rate; HR, heart rate; ISDN, isosorbide dinitrate; K, potassium; MRA, mineralocorticoid receptor antagonist; RAASi, renin–angiotensin–aldosterone system inhibitor; SBP, systolic blood pressure; SGLT2-i, sodium–glucose cotransporter 2 inhibitor. From Mullens et al.