Amplification of atherosclerotic calcification and Mönckeberg's sclerosis: a spectrum of the same disease process.

Autopsy studies have shown the near universal presence of fatty streaks and fibroatheromas in the general population from which chronic kidney disease (CKD) patients arise. The vast majority of CKD patients have multiple conventional cardiovascular risk factors. Atherosclerosis, once present, can predominantly manifest as medial calcification, which has been previously termed Mönckeberg's sclerosis. This term has also been used in rare cases to describe vascular calcinosis not related to CKD. This clarification is critical to advance the field in terms of pathological diagnosis and treatment of CKD bone and mineral disorder. Factors that appear to promote the osteoblastic transformation of vascular smooth muscle cells and enhance deposition of calcium hydroxyapatite crystals include phosphorus activation of the Pit-1 receptor, bone morphogenic proteins 2 and 4, leptin, endogenous 1,25 dihydroxy vitamin D, vascular calcification activating factor, and measures of oxidative stress. These entities work to accelerate the atherosclerotic process in CKD patients and may be future targets for diagnosis and treatment. Although conventional atherosclerotic risk factors should be optimally managed, it should be noted that trials of hydroxymethylglutaryl-CoA reductase inhibitors have failed to attenuate the rate of progressive vascular calcification as measured by computed tomography scans.

Accelerated atherosclerotic calcification and Monckeberg's sclerosis: a continuum of advanced vascular pathology in chronic kidney disease.

Autopsy studies have demonstrated the near universal presence of fatty streaks and fibroatheromas in the general population from which patients with chronic kidney disease (CKD) arise. The vast majority of patients with CKD have multiple conventional cardiovascular risk factors. Vascular atherosclerotic calcification develops in most patients as they transition from the general population to significant CKD as part of cholesterol crystallization within atherosclerotic lesions. Once present, however, atherosclerotic medial calcification can become prominent and has been previously identified as Mönckeberg's sclerosis. A unifying concept supported by the preponderance of pathologic evidence contends that Mönckeberg's sclerosis is a manifestation of accelerated atherosclerosis in patients with CKD. The term has also been used in rare cases to describe vascular calcinosis not related to CKD. This clarification is critical to advance the field in terms of pathologic diagnosis and treatment of CKD bone and mineral disorder. Factors that seem to promote the osteoblastic transformation of vascular smooth muscle cells and enhance deposition of calcium hydroxyapatite crystals include phosphorus activation of the Pit-1 receptor, bone morphogenic proteins 2 and 4, leptin, endogenous 1,25 dihydroxyvitamin D, vascular calcification activating factor, and measures of oxidative stress. These entities work to accelerate the atherosclerotic process in patients with CKD and may be future targets for diagnosis and treatment because randomized trials with hydroxymethylglutaryl-CoA reductase inhibitors have failed to attenuate the rate of progressive vascular calcification.