TY - JOUR
T1 - Patients with advanced chronic kidney disease and vascular calcification have a large hydrodynamic radius of secondary calciprotein particles
AU - Chen, Wei
AU - Anokhina, Viktoriya
AU - Dieudonne, Gregory
AU - Abramowitz, Matthew K.
AU - Kashyap, Randeep
AU - Yan, Chen
AU - Wu, Tong Tong
AU - De Mesy Bentley, Karen L.
AU - Miller, Benjamin L.
AU - Bushinsky, David A.
N1 - Funding Information:
This research was supported by the University of Rochester Clinical and Translational Science award (KL2 TR001999) from the National Center for Advancing Translational Sciences of the National Institutes of Health (W.C.), American Society of Nephrology Carl W. Gottschalk Research Grant (W.C.) and the Renal Research Institute (W.C. and D.A.B.); and the National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK075462) (D.A.B). The Dynamic Light Scattering DynaPro Plate Reader II was supported by National Center for Research Resources grants 1S10 RR026501 and 1S10 RR027241, as well as National Institute of Allergy and Infectious Diseases P30 AI078495 and the School of Medicine and Dentistry, University of Rochester. Transmission electron microscopy was supported by the University of Rochester Medical Center electron microscopic shared resource.
Publisher Copyright:
© The Author(s) 2018.
PY - 2019/6/1
Y1 - 2019/6/1
N2 - Background. The size of secondary calciprotein particles (CPP2) and the speed of transformation (T50) 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 (Rh) of CPP1 and CPP2, T50 and aggregation of CPP2.We used this DLS assay to test the hypothesis that a large Rh of CPP2 and/or a fast T50 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 score6 or an Adragao score-3. Results. CKD participants with VC had larger cumulants Rh 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), P0.01 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 Rh of CPP2, after adjusting for age, diabetes, serum calcium and phosphate [odds ratio 1.09, 95% confidence interval (CI) 1.03, 1.16, P0.005]. The area under the receiver operating characteristic curve for VC of CPP2 size was 0.75 (95% CI 0.60, 0.90). T50 was similar in CKD participants with and without VC, although both groups had a lower T50 than HV. Conclusions. Rh of CPP2, but not T50, is independently associated with VC in patients with CKD Stages 4-5.
AB - Background. The size of secondary calciprotein particles (CPP2) and the speed of transformation (T50) 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 (Rh) of CPP1 and CPP2, T50 and aggregation of CPP2.We used this DLS assay to test the hypothesis that a large Rh of CPP2 and/or a fast T50 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 score6 or an Adragao score-3. Results. CKD participants with VC had larger cumulants Rh 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), P0.01 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 Rh of CPP2, after adjusting for age, diabetes, serum calcium and phosphate [odds ratio 1.09, 95% confidence interval (CI) 1.03, 1.16, P0.005]. The area under the receiver operating characteristic curve for VC of CPP2 size was 0.75 (95% CI 0.60, 0.90). T50 was similar in CKD participants with and without VC, although both groups had a lower T50 than HV. Conclusions. Rh of CPP2, but not T50, is independently associated with VC in patients with CKD Stages 4-5.
KW - Calcification propensity
KW - Calciprotein particle
KW - Chronic kidney disease
KW - Mineral metabolism
KW - Vascular calcification
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U2 - 10.1093/ndt/gfy117
DO - 10.1093/ndt/gfy117
M3 - Article
C2 - 29788425
AN - SCOPUS:85067116360
SN - 0931-0509
VL - 34
SP - 992
EP - 1000
JO - Proceedings of the European Dialysis and Transplant Association - European Renal Association. European Dialysis and Transplant Association - European Renal Association. Congress
JF - Proceedings of the European Dialysis and Transplant Association - European Renal Association. European Dialysis and Transplant Association - European Renal Association. Congress
IS - 6
ER -
