Worsening calcification propensity precedes all-cause and cardiovascular mortality in haemodialyzed patients

Georg Lorenz,Axel Bauer,Wilhelm Koch-Sembdner,Christoph Schmaderer,Philipp Moog,Quirin Bachmann,Dominik Steubl,Maciej Lech,Susanne Angermann,Dang Pham,Christopher C Mayer,Siegfried Wassertheurer,Stephan Kemmner,Andreas Pasch,Uwe Heemann,Bernhard Haller

doi:10.1038/s41598-017-12859-6

Abstract

A novel in-vitro test (T50-test) assesses ex-vivo serum calcification propensity which predicts mortality in HD patients. The association of longitudinal changes of T50 with all-cause and cardiovascular mortality has not been investigated. We assessed T50 in paired sera collected at baseline and at 24 months in 188 prevalent European HD patients from the ISAR cohort, most of whom were Caucasians. Patients were followed for another 19 [interquartile range: 11–37] months. Serum T50 exhibited a significant decline between baseline and 24 months (246 ± 64 to 190 ± 68 minutes; p < 0.001). With serum Δ-phosphate showing the strongest independent association with declining T50 (r = −0.39; p < 0.001) in multivariable linear regression. The rate of decline of T50 over 24 months was a significant predictor of all-cause (HR = 1.51 per 1SD decline, 95% CI: 1.04 to 2.2; p = 0.03) and cardiovascular mortality (HR = 2.15; 95% CI: 1.15 to 3.97; p = 0.02) in Kaplan Meier and multivariable Cox-regression analysis, while cross-sectional T50 at inclusion and 24 months were not. Worsening serum calcification propensity was an independent predictor of mortality in this small cohort of prevalent HD patients. Prospective larger scaled studies are needed to assess the value of calcification propensity as a longitudinal parameter for risk stratification and monitoring of therapeutic interventions.

Highlights

A novel in-vitro test (T50-test) assesses ex-vivo serum calcification propensity which predicts mortality in HD patients
This study was performed in a subgroup of 188 European haemodialysis patients of the in end stage Renal disease” - (ISAR) cohort who were still alive and active in the study after the first follow up (FU) period of 24 months with a maximum spread of ± 3.2 months and for whom sera were available at both baseline and FU
The main findings of this subgroup analysis in chronic haemodialysis patients, were, firstly, that serum calcification propensity T50 declined between baseline and FU

Summary

Introduction

A novel in-vitro test (T50-test) assesses ex-vivo serum calcification propensity which predicts mortality in HD patients. Worsening serum calcification propensity was an independent predictor of mortality in this small cohort of prevalent HD patients. Disturbed calcium and phosphate homeostasis, vascular disease progression and excess mortality, largely attributable to cardiovascular (CV) causes, remain unresolved issues in haemodialysis (HD) patients. Pasch et al developed an in-vitro test (T50-test), that time-dependently assesses the calcification propensity of human serum in the presence of supersaturating doses of calcium and phosphate. Pasch et al developed an in-vitro test (T50-test), that time-dependently assesses the calcification propensity of human serum in the presence of supersaturating doses of calcium and phosphate5,6 In this process, amorphous primary calciprotein particles (CPP) spontaneously grow into crystallized secondary CPP5.

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Conclusion