â€œThis decline occurs before there is any elevation in serum phosphorus,â€ Dr. William Goodman, Professor of Medicine, David Geffen School of Medicine, noted.
Abnormalities in vitamin D metabolism in turn adversely affect intestinal calcium transport.
Thus, in Dr. Goodmanâ€™s view, elevations in PTH in early-stage CKD is an appropriate physiological response that helps maintain serum calcium levels.
In both healthy individuals as well as in patients with mild to moderate CKD, phosphorus loading impairs the kidneyâ€™s production of 1,25-dihydroxyvitamin D3, while restricting phosphorus will increase its production.
The literature suggests that even if phosphorus level is normal, restricting phosphorus in the diet or through the use of phosphate binders will drive up 1,25-dihydroxy-vitamin D3 production and help prevent bone disease.
Increases in 1,25-dihydroxyvitamin D3 levels correspond with subsequent reductions in plasma PTH levels, â€œso it is the change in circulating 1,25-dihydroxyvitamin D3 levels that mediates the reduction in PTH, not phosphorus per se,â€ Dr. Goodman
also argued that patients with earlier-stage CKD are fundamentally different than those on dialysis, largely because they still have residual kidney function and they can excrete phosphorus.
In patients who have mild to moderate CKD, serum phosphorus levels are usually normal, while serum calcium levels are typically in the lower range of normal, he
added; and the fact that patients with mild CKD excrete relatively little calcium is a sign that the kidney is trying to conserve calcium. â€œIâ€™m not arguing with the fact that phosphate restriction and phosphate binders are appropriate when serum phosphate levels are elevated,â€ Dr. Goodman
Data supporting a non-calcium-based phosphate binder strategy are limited but one prospective studyâ€"the â€œtreat-to-goalâ€ trialâ€"showed that vascular calcification did not worsen over one year of follow-up in dialysis patients treated with sevelamer, whereas it did progress in patients treated with a calcium phosphate binder. â€œTheoretically, the use of lanthanum carbonate might have a similar beneficial effect because it is also calcium-free,â€ Dr. Goodman
indicated, although this has not yet been demonstrated in a prospective trial.
stated that the choice of a phosphate binding agent could influence progression of calcification once it is present, even though it is not clear how vascular calcification develops in the first place.
â€œYour choice of phosphate binder is going to be influenced very significantly by other biochemical abnormalities,â€ Dr. Goodman
In an interview, Dr. Goodman
also suggested that this agent might be equivalent in potency to the old aluminum-containing binders and more potent than calcium carbonate nor calcium acetate.