The mineral and bone disorders of chronic kidney disease (CKD-MBD) comprise dangerous complications of kidney disease given their contribution to vascular calcification and heart failure. Hyperphosphataemia is associated with secondary hyperparathyroidism but is generally thought to contribute to this only in late-stage chronic kidney disease (CKD), since serum phosphate tends to remain within the reference range in earlier stages. However, we would like to access the Biobank data to see whether phosphate levels actually begin to rise earlier in CKD’s progression (albeit within the reference range). In 2019, we reported the likely mechanism by which high phosphate acts, namely as a non-competitive antagonist of the calcium-sensing receptor (CaSR) which controls PTH release (Centeno et al., 2019, Nature Comms; and then Goodman et al., 2022 J Am Soc Nephrol). Since the CaSR was found to be relatively sensitive to phosphate changes even over the physiological range, then if phosphate levels begin to rise earlier in CKD than previously thought (even if within the reference range), then this could give nephrologists an earlier target for therapeutic intervention. We would further wish to look for associations between other mineral markers including serum calcium and vitamin D levels as well as markers of bone loss by i) CKD staging, ii) month (given seasonal vitamin D changes), iii) age (we tend towards renal decline and secondary hyperparathyroidism as we age – contributing to vascular calcification), and iv) by progression to acute pancreatitis (another life-threatening disease involving mineral dysfunction whose incidence is higher in people with loss-of-function CaSR mutations).
