Abstract
Patients with chronic kidney disease (CKD) are highly susceptible to cardiovascular (CV) complications, thus suffering from clinical manifestations such as heart failure and stroke. CV calcification greatly contributes to the increased CV risk in CKD patients. However, no clinically viable therapies towards treatment and prevention of CV calcification or early biomarkers have been approved to date, which is largely attributed to the asymptomatic progression of calcification and the dearth of high-resolution imaging techniques to detect early calcification prior to the ‘point of no return’. Clearly, new intervention and management strategies are essential to reduce CV risk factors in CKD patients. In experimental rodent models, novel promising therapeutic interventions demonstrate decreased CKD-induced calcification and prevent CV complications. Potential diagnostic markers such as the serum T50 assay, which demonstrates an association of serum calcification propensity with all-cause mortality and CV death in CKD patients, have been developed. This review provides an overview of the latest observations and evaluates the potential of these new interventions in relation to CV calcification in CKD patients. To this end, potential therapeutics have been analyzed, and their properties compared via experimental rodent models, human clinical trials, and meta-analyses.
Highlights
Interaction between organs is of growing relevance given the increasing number of elderly patients with many comorbidities and the recognition that such comorbidities influence the clinical course of a given disease and its prognosis, and affect treatment options and therapeutic success [1]
A Cochrane systematic review and meta-analysis of randomized clinical trials (RCT) showed that sevelamer compared to calcium-based PB (CBB) decreased all-cause mortality in end-stage renal disease (ESRD) patients [36], while sevelamer had no effect on CV mortality [37]
Phosphate binders (PB) inhibit the gastrointestinal uptake of vitamin K2, aggravating vitamin K deficiency in chronic kidney disease (CKD) patients [78]
Summary
Interaction between organs is of growing relevance given the increasing number of elderly patients with many comorbidities and the recognition that such comorbidities influence the clinical course of a given disease and its prognosis, and affect treatment options and therapeutic success [1]. The International of Nephrology (ISN) recommends frequent monitoring recommends frequent monitoring of serum levels of calcium, phosphate, and PTH, starting in of serum levels of calcium, phosphate, and PTH, starting in CKD stage 3 patients [11]. Modifications in the circulation as well as in the myocardium are crucially involved in the Modifications in the circulation as well as in the myocardium are crucially involved in the increased CV risk in CKD patients. Both the mediators and the underlying molecular increased CV risk in CKD patients Both the mediators and the underlying molecular mechanisms remain largely unexplored [12]. The extent of CV calcification depends on the CKD stage [16,17]
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