Dr Mark Tiong1,2, Dr MICHAEL MX CAI1,2, Prof NIGEL D TOUSSAINT1,2, Dr SVEN-JEAN TAN1,2, Dr ANDREAS PASCH3,4,5, A/PROF EDWARD R SMITH1,2
1Department of Nephrology, The Royal Melbourne Hospital, Parkville, Australia, 2Department of Medicine (RMH), The University of Melbourne, Parkville, Australia, 3Calciscon AG, Biel, Switzerland, 4Lindenhofspital Bern, Bern, Switzerland, 5Department of Physiology and Pathophysiology, Johannes Kepler University, Linz, Austria
Aim
To examine the acute effect of nutritional loading on calciprotein particles (CPP) in healthy adults and individuals with impaired kidney function.
Background
Plasma approaches metastability with respect to its calcium and phosphate content, with only minor ionic perturbations needed to sustain crystal growth once nucleated. Additionally, calcium and phosphate are intermittently absorbed from the diet each day, yet plasma concentrations of these ions deviate minimally post-prandially. This implies the existence of a blood-borne mineral buffer system to sequester calcium phosphates and minimise the risk of deposition in the soft tissues. CPP, endogenous mineral-protein colloids containing the plasma protein fetuin-A, may fulfill this function but definitive evidence linking dietary mineral loading with their formation is lacking.
Methods
After an overnight fast, participants received a standardised meal and serial blood samples were collected over 4 hours. We measured amorphous (CPP-I) and crystalline (CPP-II) serum CPP, its precursor calciprotein monomers (CPM) and the ability of serum to resist CPP-II formation ex vivo (T50-test), in 16 healthy adults and 14 individuals with CKD.
Results
We observed significant post-prandial increases in serum CPM, CPP-I and CPP-II in control and CKD groups, despite minimal change in conventional mineral markers, including serum calcium, phosphate, magnesium, bicarbonate and the major phosphaturic hormones parathyroid hormone and fibroblast growth factor-23. This was accompanied by an acute transient increase in T50, concomitant with a rise in fetuin-A. In the CKD group, fasting CPM levels were higher compared to controls, and post-prandial excursions of CPM were markedly augmented, the magnitude of which was strongly inversely correlated with glomerular filtration rate.
Conclusions
These findings reveal that CPM and CPP are formed as a normal physiological response to feeding, but that CPM metabolism is dysregulated in CKD, likely secondary to reduced renal clearance.
Biography:
Dr Mark Tiong completed his RACP fellowship in nephrology in 2019 and currently works as a nephrologist in the Department of Nephrology at The Royal Melbourne Hospital. He is also currently undertaking his PhD in the area of Chronic Kidney Disease – Mineral and Bone Disorder (CKD-MBD) within the Department of Medicine (RMH) at The University of Melbourne.