Accelerated Atherosclerotic Calcification and Mo[Combining Diaeresis]nckeberg's Sclerosis

Abstract

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 Mö nckeberg's sclerosis. A unifying concept supported by the preponderance of pathologic evidence contends that Mö nckeberg'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.

Effect of Renin Angiotensin System Blockade on Pentraxin 3 Levels in Type-2 Diabetic Patients With Proteinuria

“…Multiple pathways have been demonstrated to link CKD to inflammation and endothelial damage (21), including, but not limited to, a decreased clearance of proinflammatory cytokines (22), increased asymmetric dimethylarginine levels (6), and an increased oxidative stress (23). A previously reported accelerated development of atherosclerotic CVD (24) and vascular calcification (24) in uremia may also contribute. The target of ACE inhibition, angiotensin II, is itself an important inducer of vascular injury in several inflammatory settings other than uremia (25), where it induces endothelial dysfunction (25) and CRP generation (26), enhances vascular remodeling (25), and accelerates the progression of atherosclerosis (25).…”

Vascular Calcification in Predialysis CKD

“…The relationship between intimal and medial calcification is controversial and of interest in the nephrology community (10)(11)(12). Intimal and medial calcification are definitely related, have similar risk factors, and develop in parallel.…”

“…Intimal and medial calcification are definitely related, have similar risk factors, and develop in parallel. Some have suggested that they are a continuum of vascular pathology (12). Clinically, it is difficult to differentiate them.…”

Peripheral Arterial Disease Predicts Overall and Cardiovascular Mortality in Peritoneal Dialysis Patients

“…Other limitations in this study are that we did not differentiate medial artery calcification, which is a common complication in ESRD patients 27 from atherosclerotic PAD.…”