Hypertension and cardiomyopathy associated with chronic kidney disease: epidemiology, pathogenesis and treatment considerations

Figures

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  Fig. 1. CKD-associated cardiomyopathy. CKD-associated cardiomyopathy is characterised by structural remodelling of the heart. Diffuse interstitial fibrosis and cardiac hypertrophy give rise to cardiac electromechanical dysfunction and increased risk of sudden death.

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  Fig. 2. Activated human induced pluripotent stem cell-derived cardiac fibroblasts. Laser scanning confocal image of human induced pluripotent stem cell-derived cardiac fibroblasts activated by transforming growth factor-β stained with antibodies against α-smooth muscle actin (green) and vimentin (red). Every third to fourth cell in the left ventricle is a fibroblast. Most cardiac research has focused on the cardiomyocyte with research on cardiac fibroblasts proving more challenging. (Image provided by Ms Caitlin Hall, Institute of Cardiovascular Sciences, University of Birmingham).

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  Fig. 3. Cardiac magnetic resonance images demonstrating left ventricular hypertrophy and normal dimensions in dialysis patients. Short axis stack image (A) and horizontal long axis image (B) of a patient on haemodialysis with concentric left ventricular hypertrophy on cardiac magnetic resonance imaging (maximum wall thickness, 15 mm; left ventricular mass 93 g/m2). Short axis stack image (C) and horizontal long axis image (D) of a patient on peritoneal dialysis with normal left ventricular dimensions on cardiac magnetic resonance imaging (maximum wall thickness, 9 mm; left ventricular mass 63 g/m2).

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  Fig. 4. T1 cardiac magnetic resonance images demonstrating different levels of left ventricular fibrosis in dialysis patients. T1 mapping of the short axis stacked image of the mid left ventricular cavity (A) (Global T1 time 1385 ms) and (B) (Global T1 time 1170 ms) of 2 peritoneal dialysis patients consistent with high and low levels of cardiac fibrosis respectively.

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  Fig. 5. Pathogenesis of CKD-associated cardiomyopathy. An interplay of pathophysiological processes associated with the chronic kidney disease milieu contribute to the pathogenesis of CKD-associated cardiomyopathy. These can be broadly divided into factors which increase afterload, preload, and those which result from maladaptive perturbations of intrinsic factors. AGEs advanced glycation end-products, FGF23 fibroblast growth factor 23, PTH parathyroid hormone, RAAS renin-angiotensin-aldosterone system, SNS sympathetic nervous system.

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  Fig. 6. Effect of dialysis regimen on blood pressure, cardiac and other outcomes. Conventional haemodialysis regimens consist of a four-hour haemodialysis session delivered on alternate days, three times per week. Longer, more frequent dialysis regimens have been trialled, with benefits on blood pressure, left ventricular mass, mortality, hospitalisations, and quality of life. However, the implementation of such ‘intensive’ regimens significantly increases the demand on healthcare providers and may be associated with risks of infection, vascular access complications and loss of residual kidney function.

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  Fig. 7. Blood pressure management in chronic kidney disease. The recently updated Kidney Diseases Improving Global Outcomes (KDIGO) 2021 Blood Pressure Guideline provides clear recommendations for the management and benefits of blood pressure control in patients with CKD (incl. transplant recipients).

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  Fig. 8. Comparing the cardiac effects of conventional antihypertensive therapy. Several landmark trials and meta-analyses have compared the efficacy of antihypertensive drug classes on cardiac functional, structural, and mortality endpoints.

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  Fig. 9. Pleiotropic effects of sodium-glucose cotransporter type 2 inhibition. Sodium-glucose cotransporter type 2 inhibitors have traditionally been an effective antidiabetic therapy. Recent trials have demonstrated a multitude of beneficial cardiorenal, metabolic and vascular effects, which underpin the improvement in cardiovascular and renal outcomes independent of improved glycaemic control. Some of these mechanisms have been summarised.

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  Fig. 10. Cardiovascular consequences of CKD-MBD. Chronic kidney disease – mineral bone disorder (CKD-MBD) describes the alterations in circulating and tissue levels of calcium and phosphate because of changes in parathyroid hormone, vitamin D, fibroblast growth factor 23 (FGF23) and its coreceptor Klotho. These biochemical changes are associated with the cardiovascular remodelling and clinical manifestations observed in patients with CKD.