Calcification Propensity of Serum is Independent of Excretory Renal Function

Bernhard Bielesz,Andreas Gleiss,Marija Bojic,Rodrig Marculescu,Heidi Kieweg,Thomas Reiter,Daniel Cejka

doi:10.1038/s41598-017-18336-4

Abstract

Vascular calcification is a component of cardiovascular disease, which is leading cause of death in patients with chronic kidney disease (CKD). A functional assay (T50-test) measuring the propensity of human serum to calcify associates with mortality and cardiovascular events in CKD patients. Calcification propensity is known to increase with CKD stage. We investigated whether the T50 readout is directly dependent on excretory kidney function (eGFR) or rather explained by deranged parameters of bone and mineral metabolism in the course of CKD. T50, along with markers implicated in calcification and mineral metabolism, were measured in a cross-sectional cohort of 118 patients with CKD stage 1–5. Associations of T50 with measured parameters were analysed and partial correlations performed to test to which extent the association of T50 with eGFR can be attributed to variation of these parameters. T50 correlates with eGFR, but serum levels of phosphate and calcium largely explain this association. Phosphate, magnesium, fetuin A, albumin, bicarbonate, and serum cross-laps but not Parathyroid Hormone or Fibroblast Growth Factor 23 are associated with T50 in multivariate adjusted models. These findings indicate that T50 values depend mainly on the concentration of promoters and inhibitors of calcification in serum, but not excretory kidney function.

Highlights

Chronic kidney disease (CKD) is associated with increased all-cause and cardiovascular mortality[1]
Serum Fetuin A, serum magnesium (Mg), phosphate, and intact Fibroblast Growth Factor 23 showed a statistically significant influence on T50 after adjusting for age, gender, and eGFR (Table 2) with a proportion of T50 variation explained by age, gender, eGFR and the respective marker above 30% (R2 > 0.3)
After additional adjustment for phosphate, intact Fibroblast Growth Factor 23 (iFGF23) and 1,25(OH)2D were no longer significantly associated with T50, indicating that these relationships are mainly mediated by phosphate (Table S1)

Summary

Introduction

Chronic kidney disease (CKD) is associated with increased all-cause and cardiovascular mortality[1]. As renal function declines patients uniformly develop hyperphosphatemia, increased levels of parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) All these factors have been associated with adverse clinical outcomes and increased mortality[4,5]. PTH, and FGF23, T50 associates with glomerular filtration rate thereby linking impaired calcification resistance with kidney function decline. It is currently unclear whether this association is already sufficiently explained by abnormalities in mineral metabolism (such as hyperphosphatemia), which are the consequence of CKD or rather mediated by reduced nephron mass along with a large number of known and unknown uremic toxins. We further estimated the quantitative role of excretory renal function per se on calcification propensity in light of the observed alterations of mineral metabolism markers in progressive stages of chronic kidney disease

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