Vascular calcification (VC) strongly correlates with declining renal function and contributes to the high morbidity and mortality of patients with CKD (chronic kidney disease). It is closely regulated by circulating factors but little is known about the capacity of serum from patients to induce calcification outside the disease setting, which we now define as the calcific potential of serum. We have therefore examined the ability of serum from age- and sex-matched subjects with and without advancing CKD to induce calcification of cultured SMCs (smooth muscle cells). Samples from patients with CKD induced significant calcification compared with controls. More importantly, samples from patients on haemodialysis induced significantly higher calcification than those with moderate or advanced CKD. The calcification induced by the latter two but not those on haemodialysis could be enhanced with calcium chloride and β-GP (β-glycerophosphate). A positive correlation was evident between measured serum creatinine, phosphate, PTH (parathyroid hormone), OPG (osteoprotegerin) and the degree of calcification in vitro. eGFR (estimated glomerular filtration rate), DBP (diastolic blood pressure), haemoglobin and serum albumin correlated negatively. Stepwise multivariate analysis of log-transformed calcific potential data highlighted serum creatinine, albumin and OPG as significant predictors, explaining approximately 50% of the variation. Thus, other regulators, either not investigated or as yet unidentified, may contribute to the calcification potential of serum in vitro. Furthermore, uraemic serum can induce graded calcification outside of the disease milieu that reflects the degree of kidney impairment in vivo. These findings could have important clinical relevance in terms of developing novel diagnostic and/or therapeutic strategies for subjects with CKD.
Human uraemic serum displays calcific potential in vitro that increases with advancing chronic kidney disease
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Ashish Patidar, Dhruv K. Singh, Peter Winocour, Ken Farrington, Anwar R. Baydoun; Human uraemic serum displays calcific potential in vitro that increases with advancing chronic kidney disease. Clin Sci (Lond) 1 September 2013; 125 (5): 237–245. doi: https://doi.org/10.1042/CS20120638
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