Determinants of coronary artery calcification in diabetics with and without nephropathy

Mehrotra, Rajnish; Budoff, Matthew J.; Christenson, Peter; Ipp, Eli; Takasu, Junichiro; Gupta, Ajay; Norris, Keith C.; Adler, Sharon G.

doi:10.1111/j.1523-1755.2004.00974.x

Cited by 100 publications

(83 citation statements)

References 46 publications

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“…Some but not all studies that have examined the potential risk factors of coronary artery calcification among patients with CKD have implicated both the conventional risk factors such as diabetes (31) and dyslipidemia (32,33) and CKD-specific factors such as inflammation (34 -37), fetuin deficiency (38,39), SHPT (40), hypercalcemia or high calcium load (41), and high calcium-phosphorus product (42); however, there have been contradictory data about the association of some of these factors and vascular calcification. One study did not find any associations between blood levels of minerals or PTH and CACS in nondialyzed patients with CKD (43). Similarly, in our study, minerals or PTH did not correlate with CACS, but AlkPhos did.…”

Section: Discussioncontrasting

confidence: 36%

Association of Serum Alkaline Phosphatase with Coronary Artery Calcification in Maintenance Hemodialysis Patients

Shantouf¹,

Kövesdy²,

Kim³

et al. 2009

Clinical Journal of the American Society of Nephrology

141

115

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Background and objectives: Recent in vitro studies have shown a link between alkaline phosphatase and vascular calcification in patients with chronic kidney disease (CKD). High serum levels of alkaline phosphatase are associated with increased death risk in epidemiologic studies of maintenance hemodialysis (MHD) patients. We hypothesized that coronary artery calcification is independently associated with increased serum alkaline phosphatase levels in MHD patients.Design, setting, participants, & measurements: We examined the association of coronary artery calcification score (CACS) and alkaline phosphatase in 137 randomly selected MHD patients for whom markers of malnutrition, inflammation, and bone and mineral disorders were also measured.Results: Serum alkaline phosphatase was the only measure with significant and robust association with CACS (P < 0.003), whereas either other biochemical markers had no association with CACS or their association was eliminated after controlling for case-mix variables. Serum alkaline phosphatase >120 IU/L was a robust predictor of higher CACS and was particularly associated with the likelihood of CACS >400 (multivariate odds ratio 5.0 95% confidence interval 1.6 to 16.3; P ‫؍‬ 0.007). Serum alkaline phosphatase of approximately 85 IU/L seemed to be associated with the lowest likelihood of severe coronary artery calcification, but in the lowest tertile of alkaline phosphatase, the CACS predictability was not statistically significant.Conclusions: An association between serum alkaline phosphatase level and CACS exists in MHD patients. Given the high burden of vascular calcification in patients with CKD, examining potential therapeutic interventions to modulate the alkaline phosphatase pathway may be warranted.

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Section: Discussioncontrasting

confidence: 36%

Association of Serum Alkaline Phosphatase with Coronary Artery Calcification in Maintenance Hemodialysis Patients

Shantouf¹,

Kövesdy²,

Kim³

et al. 2009

Clinical Journal of the American Society of Nephrology

141

115

View full text Add to dashboard Cite

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“…(15,(40)(41)(42)(43)(44)(45)(46)(47) Treating disease at an earlier stage may have greater impact on slowing cardiovascular damage, but development of novel therapeutics is limited by an incomplete understanding of how renal dysfunction leads to cardiovascular disease. Serum phosphate has been shown to strongly correlate with these cardiovascular events, with emerging evidence that poor bone health may also contribute to phosphate imbalance.…”

Section: Discussionmentioning

confidence: 99%

Repression of osteocyte Wnt/β-catenin signaling is an early event in the progression of renal osteodystrophy

Sabbagh

Graciolli

O’Brien

et al. 2012

Journal of Bone and Mineral Research

240

224

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Chronic kidney disease–mineral bone disorder (CKD‐MBD) is defined by abnormalities in mineral and hormone metabolism, bone histomorphometric changes, and/or the presence of soft‐tissue calcification. Emerging evidence suggests that features of CKD‐MBD may occur early in disease progression and are associated with changes in osteocyte function. To identify early changes in bone, we utilized the jck mouse, a genetic model of polycystic kidney disease that exhibits progressive renal disease. At 6 weeks of age, jck mice have normal renal function and no evidence of bone disease but exhibit continual decline in renal function and death by 20 weeks of age, when approximately 40% to 60% of them have vascular calcification. Temporal changes in serum parameters were identified in jck relative to wild‐type mice from 6 through 18 weeks of age and were subsequently shown to largely mirror serum changes commonly associated with clinical CKD‐MBD. Bone histomorphometry revealed progressive changes associated with increased osteoclast activity and elevated bone formation relative to wild‐type mice. To capture the early molecular and cellular events in the progression of CKD‐MBD we examined cell‐specific pathways associated with bone remodeling at the protein and/or gene expression level. Importantly, a steady increase in the number of cells expressing phosphor‐Ser33/37‐β‐catenin was observed both in mouse and human bones. Overall repression of Wnt/β‐catenin signaling within osteocytes occurred in conjunction with increased expression of Wnt antagonists (SOST and sFRP4) and genes associated with osteoclast activity, including receptor activator of NF‐κB ligand (RANKL). The resulting increase in the RANKL/osteoprotegerin (OPG) ratio correlated with increased osteoclast activity. In late‐stage disease, an apparent repression of genes associated with osteoblast function was observed. These data confirm that jck mice develop progressive biochemical changes in CKD‐MBD and suggest that repression of the Wnt/β‐catenin pathway is involved in the pathogenesis of renal osteodystrophy. © 2012 American Society for Bone and Mineral Research.

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“…We considered two cut-off points for CAC (Ͼ100 and Ͼ400) as consistent with subclinical CVD based on prior (37). It has been reported previously that the prevalence of peripheral arterial disease in the general population is higher among African Americans than Hispanics (13,39,40).…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular Disease Among Hispanics and Non-Hispanics in the Chronic Renal Insufficiency Cohort (CRIC) Study

Ricardo

Lash

Fischer

et al. 2011

Clinical Journal of the American Society of Nephrology

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Determinants of coronary artery calcification in diabetics with and without nephropathy

Cited by 100 publications

References 46 publications

Association of Serum Alkaline Phosphatase with Coronary Artery Calcification in Maintenance Hemodialysis Patients

Association of Serum Alkaline Phosphatase with Coronary Artery Calcification in Maintenance Hemodialysis Patients

Repression of osteocyte Wnt/β-catenin signaling is an early event in the progression of renal osteodystrophy

Cardiovascular Disease Among Hispanics and Non-Hispanics in the Chronic Renal Insufficiency Cohort (CRIC) Study

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