Arterial Calcification in Chronic Kidney Disease: Whom? When? and How to Handle?

Abstract

Chronic kidney disease (CKD) patients have the highest mortality rate compared to other chronic diseases. Cardiovascular events account for up to 60% of the mortalities, with cardiovascular calcifications affecting the majority of those CKD patients. Most of this calcification is related to disturbed renal phosphate handling. Fibroblast growth factor 23 (FGF23) and Klotho were incriminated in the pathogenesis of vascular calcification (VC) through different mechanisms including their effect on endothelium and arterial wall smooth muscle cells. In addition, deficient Klotho gene expression is a constant feature in CKD patients. This deficiency, not only promotes vascular pathology, but also has a role in the progression of the CKD. This review will cover the medical history, prevalence, pathogenesis, clinical relevance, diagnostic tools, the ideal timing to prevent or to withhold the progression of VC and the different medications and medical procedures that can help to prolong the survival of CKD patients. IntroductionThe problematic increase of cardiovascular morbidity and mortality is behind the increased interest in VC among CKD patients. VC is a strong predictor of increased cardiovascular mortality among CKD patients. However, almost all of the clinical studies that have tried to manipulate the various risk factors for VC in dialysis patients have failed to show a significant impact on patient survival. On the other hand, when pre-dialysis patients underwent similar studies, there was a significant decrease in cardiovascular and overall mortality rates, as well as a comparable effect on VC progress rate. These results point toward the importance of early intervention. The ideal timing and dynamics of this intervention will be thoroughly discussed. VC In CKD PatientsThe prevalence of VC among pre-dialysis CKD G3-5 patients is 79% as reported in a recent study [1]. It might approach 100% in patients starting dialysis [2]. Upto 3-4 fold increase in VC has been reported in the earliest phases of CKD [3].VC in CKD can affect the tunica intima and/or the tunica media layers. Intimal calcification is mainly a feature of atherosclerosis [4]. Medial calcification is restricted to CKD and is encountered even at young ages [5,6]. Hemodialysis (HD) patients have higher calcification scores than both peritoneal dialysis (PD) and CKD G4 patients. More heavily calcified patients were significantly older and mostly male [7]. In HD patients, coronary calcification progresses steadily [8]. High serum phosphate concentration was a strong independent risk factor only in non-diabetic patients. Diabetic patients lack similar associations [9]. Patients starting dialysis at the age of 25-29 years have an expected survival 33 years less than the general populous. Arterial calcification is one of the predictors of this increased cardiovascular mortality [10].The prevalence of coronary artery calcification (CAC) in kidney transplant recipients (KTRs) is higher (61-75%) than that assessed in CKD G3, [11,12] and lower than tha...