Evaluation of the association of Wnt signaling with coronary artery calcification in patients on dialysis with severe secondary hyperparathyroidism.

BACKGROUND

Patients with end-stage renal disease have a higher risk of death from cardiovascular events, which can be mainly attributed to coronary artery calcification (CAC). Wnt signaling is involved in vascular development and may play a role in vascular calcification. This study aimed to evaluate CAC prevalence in patients on dialysis with severe secondary hyperparathyroidism (SHPT) and identify CAC risk factors.

METHODS

The study is a retrospective analysis of the severe hyperparathyroidism registration study that prospectively recruited patients on dialysis with severe SHPT who were candidates for parathyroidectomy, from October 2013 to May 2015. CAC and bone mineral density (BMD) were measured. Demographic and clinical data including calcium, phosphorus, alkaline phosphatase, intact parathyroid hormone, Dickkopf-related protein 1 (DKK1), and sclerostin levels were analyzed. CAC scores were reported in Agatston units (AU).

RESULTS

A total of 61 patients were included in this study. No CAC, mild CAC (<100 AU), moderate CAC (>100 AU), and severe CAC (>400 AU) were observed in 4.9%, 11.4%, 14.8%, and 68.9% of patients, respectively. DKK1 and sclerostin were not associated with CAC. In univariate analysis, CAC was significantly correlated with age, sex (male), total cholesterol, and intravenous pulse calcitriol (p<0.05). CAC was not inversely correlated with the BMD, T scores, or Z scores of the femoral neck (p>0.05). In multivariate analysis, the stepwise forward multiple linear regression revealed that CAC was associated with age, male sex and intravenous pulse calcitriol (p<0.05). Furthermore, serum sclerostin was positively correlated with the BMD of the femoral neck but negatively associated with intact parathyroid hormone (p<0.05). Serum sclerostin was significantly associated with severely low bone mass with Z-scores<-2.5 of the femoral neck, even when adjusted for serum intact parathyroid hormone, vitamin D status, dialysis pattern, sex, and DKK-1 (p<0.05).

CONCLUSIONS

The patients on dialysis with severe SHPT have a high prevalence of vascular calcification. Although the Wnt signaling pathway could play a role in hyperparathyroid bone disease, CAC may be mainly due to the treatment modality rather than the Wnt signaling pathway associated bone metabolism in patients on dialysis with severe SHPT.