Simultaneous Measurement of Calciprotein Particles with Different Assays and Clinical Outcomes in CKD

Key Points Multiple assays are available to measure calciprotein particles (CPP), but a direct comparison of their association with clinical outcomes is lacking. Higher levels of high-density CPP and secondary CPP were independently associated with all-cause mortality in a CKD cohort. Higher levels of low-density CPP, primary CPP, and secondary CPP were each independently associated with progression of CKD. Background Mineral metabolism abnormalities are an almost universal feature of CKD and are believed to contribute to the development of many adverse events. Calciprotein particles (CPP) form spontaneously in biological fluids from calcium and phosphate together with the glycoprotein fetuin-A. While CPP formation is a part of normal mineral homeostasis, levels are chronically elevated in CKD. Several assays have been developed to measure serum CPP, each linking high CPP levels to adverse clinical outcomes in CKD. However, direct comparisons among these assays are lacking. The aim of this exploratory study was to compare these assays to assess their association with CKD progression and mortality. Methods We measured baseline CPP levels using various methods on stored serum samples from 189 participants in a prospective observational cohort study of patients with CKD stage 3/4. Three assays were used to measure CPP: ( 1 ) ELISA (fetuin-A CPP), ( 2 ) low-density CPP (L-CPP) and high-density CPP by gel filtration, and ( 3 ) primary CPP and secondary CPP (CPP-II) by flow cytometry. We examined the association of each CPP measure with all-cause mortality and CKD progression using unadjusted and covariate-adjusted Cox proportional hazard regression models. Results In fully adjusted models, high-density CPP (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.05 to 2.23; P = 0.028) and CPP-II (HR, 3.11; 95% CI, 1.97 to 4.98; P < 0.001) were significantly associated with an increased risk of all-cause mortality. In addition, L-CPP (HR, 1.91; 95% CI, 1.43 to 2.62; P < 0.001), primary CPP (HR, 1.31; 95% CI, 1.04 to 1.65; P = 0.023), and CPP-II (HR, 1.66; 95% CI, 1.20 to 2.29; P = 0.002) were significantly associated with CKD progression. Conclusions In a cohort of patients with CKD stages 3 and 4, serum CPP-II levels demonstrated the strongest association with all-cause mortality, while L-CPP levels showed the strongest association with CKD progression.