Association of serum zinc with mineral stress in chronic kidney disease

Abstract

Background: The excessive cardiovascular mortality of patients with chronic kidney disease (CKD) could be linked to mineral stress, the biological consequence of calcium-phosphate nanoparticle exposure. This study investigated whether zinc is associated with mineral stress markers in CKD.

Methods: Zinc and T50 (serum calcification propensity) as well as hydrodynamic radius of secondary calciprotein particles (CPP2) were measured in blood donors and CKD patients with/out dialysis.

Results: Serum zinc concentrations and T50 were reduced, while CPP2 radius was increased in CKD patients. Serum zinc levels positively correlated with T50 and inversely correlated with CPP2 radius. In a hierarchical linear regression model, T50 was associated with age, calcium, phosphate, magnesium and albumin. Addition of zinc significantly improved prediction of the model, confirming an additional contribution of zinc to T50. Similar observations were made for the association of zinc and CPP2 radius, but spiking experiments indicated that zinc may stronger modify T50 than CPP2 radius. Also, urinary zinc excretion was increased in patients with kidney disease and correlated to T50 and CPP2 radius. Serum zinc further correlated with markers of arterial stiffness in blood donors and CKD patients, but these associations did not remain significant in a multivariate linear regression model.

Conclusions: Reduced serum zinc levels in CKD appear directly linked to lower T50 and associated with larger CPP2 radius. Further studies on the associations of zinc and mineral stress as well as putative therapeutic benefits of zinc supplementation are required.

Keywords: calciprotein particles; chronic kidney disease; mineral stress; serum calcification propensity; zinc.

Graphical Abstract

Figure 1:

Scatter dot plots showing median and interquartile range of (A) serum calcification propensity (T50, min, n = 477), (B) hydrodynamic radius of CPP (CPP2, nm, n = 475) and (C) serum zinc concentrations (µg/l, n = 473) in blood donors (CTR), patients with chronic kidney disease (CKD) and dialysis patients (DIA). *P < .05, ^***P < .001.

Figure 2:

Correlations of serum zinc with (A; n = 473) serum calcification propensity (T50) and (B; n = 471) hydrodynamic radius of CCP (CPP2) in the whole-study cohort. P-values are indicated in the figure.

Figure 3:

T50 (A) and hydrodynamic radius of CPP2 (B) shown as mean (bars) with individual measurements depicted as dots in serum samples from healthy volunteers (n = 5) after addition of ZnCl₂ (0–1000 µM). All T50 values for the 1 mM zinc group were above the measurement range of 570 min (indicated by arrow), and therefore excluded from statistical analysis (Dunnetts test vs CTR). ^**P < .01, ^***P < .001.

Figure 4:

Correlations of serum zinc with pulse pressure (A; n = 446) in the whole cohort, as well as pulse-wave velocity (PWV, B; n = 213), total arterial compliance index TACI (C; n = 206) and aortic augmentation index at heart rate 75 (AIX, D; n = 148) in blood donors and CKD patients. P-values are indicated in the figure.