Chronic kidney disease and valvular heart disease: State of the art

Abstract

Chronic kidney disease (CKD) and valvular heart disease (VHD) frequently coexist and are associated with a significant increase in morbidity and mortality. Their interplay is complex and multifactorial, involving shared pathophysiological mechanisms such as chronic inflammation, mineral and bone disorder, vascular and valvular calcification, and neurohormonal activation. These factors contribute to a bidirectional relationship in which each condition can exacerbate the progression and clinical consequences of the other. This review provides a comprehensive synthesis of the current evidence on the epidemiology, pathogenesis, and clinical impact of the CKD-VHD association. Special attention is given to the mechanisms underlying valvular calcification in the uremic milieu, the diagnostic challenges posed by overlapping symptoms, and the prognostic implications of valvular disease in patients with impaired renal function. Furthermore, this paper critically examines the available therapeutic options, including medical management, surgical and transcatheter interventions, and their outcomes in CKD patients. Given the limited evidence from randomized controlled trials in this population, our work also identifies key knowledge gaps and highlights future research directions, advocating for multidisciplinary approaches and tailored strategies. A better understanding of this cardio-renal interaction is crucial to optimize clinical decision-making and improve patient outcomes.

Keywords: MAC; calcification; chronic kidney disease; inflammation; valvular heart disease.

FIGURE 1

Calcification model of the AV leaflets. The fibrosa is the outermost layer of the valve, covered by qVECs and primarily composed of collagen fibers. The spongiosa is the middle layer, mainly composed of proteoglycans and GAGs. The ventricularis is the innermost layer of the valve, predominantly composed of elastic fibers and covered by qVECs. qVECs can undergo endothelial‐to‐mesenchymal transition upon adhesion molecules downregulation, becoming AVECs, while qVICs can be activated by upregulating smooth muscle protein (aSMA), becoming AVICs. Both secrete MMP‐9 and TGFβ and deposit fibers during the fibrosis process. Prolonged activity and downregulation of AVECs and AVICs can lead to differentiation into OSTs, resulting in calcium nodule nucleation and growth. Cells death can derive from entrapment in highly fibrotic or calcified areas, and the resulting dead bodies can act as feeding sites for CaNods. AV, aortic valve; qVECs, valvular endothelial cells; GAGs, glycosaminoglycans; qVICs, valvular interstitial cells; MMP‐9, matrix metalloproteinase‐9; TGFβ, transforming growth‐factor β. Picture derived from article “Multiscale computational modeling of aortic valve calcification” by Azimi‐Boulali et al. (2024). Reprinted with permission.

FIGURE 2

Valvular calcifications and MAC. CT scan showing a case of MAC in axial view, with diffuse calcifications of both the mitral and aortic valve; coronary angiography showing calcification of the mitral anulus (arrow). MAC, mitral annular calcification.

FIGURE 3

Transthoracic and transesophageal echocardiography. a–b: Apical 2 chamber view showing mitral regurgitation with calcifications of mitral leaflets and anulus (first two panels); c: Enlarged mid‐esophageal long‐axis view emphasizing aortic valve thickening, reduced systolic opening and calcifications in a CKD patient (last panel). CKD, chronic kidney disease.

FIGURE 4

Cardiac CT scan. Cardiac CT showing calcific deposits on the mitral valve in high‐definition images, with involvement of both the anterior and posterior emiannuli (first panel); other cardiac CT images revealing a severe case of MAC, with huge calcifications of the mitral annulus and leaflets but also diffuse calcifications of the aortic valve and innominate artery, with some plaques in the ascending aorta (last two panels).