Background and objectives: Vitamin K-dependent matrix Gla protein (MGP) acts as a calcification inhibitor in vitro and in vivo. The present study was performed to (1) determine plasma levels of the inactive, dephosphorylated, uncarboxylated MGP (dp-ucMGP) in a cohort of patients at different stages of chronic kidney disease (CKD) and (2) evaluate the association between dp-ucMGP levels on one hand and aortic calcification and mortality on the other.Design, setting, participants, & measurements: 107 patients (67 ؎ 13 years; 60% male; 32% at CKD stages 2 to 3, 31% at stages 4 to 5, 37% at stage 5D) were assayed for dp-ucMGP and underwent multislice spiral computed tomography scans to quantify aortic calcification at baseline. They were prospectively monitored for mortality.Results: Plasma dp-ucMGP levels augmented progressively with CKD stage, with a significant difference from CKD stage 4. CKD stage, hemoglobin, age, and coumarin use were independently associated with plasma dp-ucMGP levels. Furthermore, plasma dp-ucMGP and age were positively and independently associated with the aortic calcification score. During follow-up (802 ؎ 311 days), 34 patients died (20 from cardiovascular events). In a crude analysis, [plasma dp-ucMGP] > 921 pM was associated with overall mortality; this association was lost after adjusting for both age and the calculated propensity score.Conclusions: Plasma dp-ucMGP increased progressively in a CKD setting and was associated with the severity of aortic calcification. Plasma dp-ucMGP could thus be a surrogate marker for vascular calcification in CKD.Clin J Am Soc Nephrol 5: 568 -575, 2010. doi: 10.2215/CJN.07081009 C ardiovascular diseases account for 50% of all deaths in a chronic kidney disease (CKD) setting (1). Vascular calcification (VC) in the media-intimal arterial layers contributes significantly to the greater mortality in this population (2,3). In fact, it has been repeatedly demonstrated that patients suffering from advanced CKD present VC to a greater extent than individuals with normal renal function (4 -7). Although many factors may influence the occurrence and progression of this condition, the fact that 20% to 40% of the patients in most CKD cohorts (8 -10) do not develop detectable VC (despite exposure to well-known environmental triggers, such as uremia, diabetes, and hyperphosphatemia) suggests that naturally occurring VC inhibitors have an important role in preventing this disease process.Matrix Gla protein (MGP) is a 10-kD protein secreted by chondrocytes and vascular smooth muscle cells in the arterial media (11). It is the first protein known to act as a calcification inhibitor in vivo (12)(13)(14), probably by directly inhibiting calcium precipitation and crystallization in the vessel wall (15) and antagonizing bone morphogenetic protein-2 (which regulates osteoblast differentiation, and thus bone formation (16)). In particular, MGP only exerts its anticalcification activity after posttranslational ␥-glutamyl carboxylation of five glutamate residues-a crucial ac...

URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01358513, NCT02132026, NCT00338676, NCT00647088, NCT01679431.

Our data suggest that plasma FGF23 is an independent biomarker of vascular calcification in patients with various CKD stages including early stages. The association between vascular calcification and FGF23 levels appears to be independent of BMD. It remains to be seen whether this association is independent of bone turnover and bone mass.

Introduction and aims: Vascular calcification is common in patients suffering from advanced chronic kidney disease (CKD), yet little is known about vascular calcification and arterial stiffness in the early stages of renal dysfunction. We evaluated, in patients suffering from CKD 3, the arterial vascular damage by means of the measurement of arterial stiffness and the coronary calcium score. Methods: Eleven patients (7 M, 4 f, aged 64±7 years) with mild to moderate renal failure were enrolled. We deliberately excluded patients with diabetes and previous history of heart disease from this study; we did this in order to exclude the interference of other pathologies apart from functional kidney insufficiency in the genesis of vascular alterations. the causes of renal failure were nephroangiosclerosis (73%), membranous glomerulonephritis (18%), and interstitial nephritis (9%). all the patients underwent the assessment of coronary calcification by means of multi-detector Ct (expressed as calcium score [Cs] according to agatston score), arterial stiffness by pulse wave velocity (pWV) measurement, common carotid intima-media thickness (iMt) by B-mode Us scan, and left ventricular mass index by echocardiography. renal function (Gfr) was evaluated using the Cockroft and Gault formula. Blood samples were drawn for the measurement of serum creatinine, lipid profile, glycidic profile, electrolytes, hOMa index, etc. Results: the main results are summarized in the table. Whilst the calcium score (Cs) was abnormal in only one patient (the remaining patients had a Cs <50 hU), the pWV and iMt were high in all of them. No substantial alterations in the lipid profile and hOMa index were present. Conclusions: Our data, albeit obtained in a small number of patients, show that in the early stages of chronic renal failure, in the absence of diabetes and cardiac involvement, vascular calcification is only rarely present. On the contrary, arterial stiffening, as shown by pWV and iMt, starts very early, even in the presence of a normal lipid profile and insulin resistance. further studies in larger groups are needed to confirm this results, as well as to understand at which moment or which factors lead to the development of the extensive vascular calci-fication observable in the advanced stages of CKD. Table. Results Variable Mean±SD GFR, mL/min 40.6±10 Total cholesterol, mg/dL 198±35 LDL cholesterol, mg/dL 111±29 HDL cholesterol, mg/dL 53±16 Triglycerides, mg/dL 183±93 HOMA index, % 1.9±1.5 PWV, m/sec 10.5±1.6 ccIMT, mm 0.8± 1.2 LVM index, g/m 2 110±41 CS (HU)* 0-1074 *Expressed as range. increased pulse wave velocity (pWV), a marker of arterial stiffness, is considered a strong predictor of cardiovascular mortality both in general and in the renal-disease population. however, it is unknown whether it may be affected by the rapid variations in the fluid status induced by treatment in dialysis (hD) patients. We studied 13 patients (6 M, 7 f, 65±12 years) on thrice-weekly chronic hD treatment in a study session after the longest interdial...

The persistence of a left superior vena cava (LSVC) is an intrinsically cardiac anomaly, which can lead to serious complications during catheterization via the subclavian or internal jugular vein. We found this anomaly during dissection associated with an abnormal origin of the vertebral artery originating from the aortic arch between the left common carotid and subclavian arteries. The LSVC coursed towards the right atrium through a very dilated coronary sinus ostium. No abnormality of the azygos system was found. A thorough anatomic description was then made with external and internal morphology. The embryonic development and variations are described. Radiological and clinical implications are discussed.