Patients with advanced chronic kidney disease and vascular calcification have a large hydrodynamic radius of secondary calciprotein particles

Background The size of secondary calciprotein particles (CPP2) and the speed of transformation (T-50) from primary calciprotein particles (CPP1) to CPP2 in serum may be associated with vascular calcification (VC) in patients with chronic kidney disease (CKD). Methods We developed a high throughput, microplate-based assay using dynamic light scattering (DLS) to measure the transformation of CPP1 to CPP2, hydrodynamic radius (R-h) of CPP1 and CPP2, T-50 and aggregation of CPP2. We used this DLS assay to test the hypothesis that a large R-h of CPP2 and/or a fast T-50 are associated with VC in 45 participants with CKD Stages 4-5 (22 without VC and 23 with VC) and 17 healthy volunteers (HV). VC was defined as a Kauppila score>6 or an Adragao score3. Results CKD participants with VC had larger cumulants R-h of CPP2 {370nm [interquartile range (IQR) 272-566]} compared with CKD participants without VC [212nm (IQR 169-315)] and compared with HV [168nm (IQR 145-352), P<0.01 for each]. More CPP2 were in aggregates in CKD participants with VC than those without VC (70% versus 36%). The odds of having VC increased by 9% with every 10nm increase in the R-h of CPP2, after adjusting for age, diabetes, serum calcium and phosphate [odds ratio 1.09, 95% confidence interval (CI) 1.03, 1.16, P=0.005]. The area under the receiver operating characteristic curve for VC of CPP2 size was 0.75 (95% CI 0.60, 0.90). T-50 was similar in CKD participants with and without VC, although both groups had a lower T-50 than HV. Conclusions R-h of CPP2, but not T-50, is independently associated with VC in patients with CKD Stages 4-5.