Phosphate (Pi) retention is a common problem in patients with
chronic kidney disease, particularly in those who have reached
end-stage renal disease (
ESRD). In addition to causing
secondary hyperparathyroidism and
renal osteodystrophy, recent evidence suggests that, in
ESRD patients, high serum
phosphorus concentration and increased
calcium and phosphorous (Ca x P) product are associated with vascular and cardiac calcifications and increased mortality.
Dietary phosphorus restriction and Pi removal by dialysis are not sufficient to restore Pi homeostasis. Reduction of intestinal Pi absorption with the use of Pi binders is currently the primary treatment for Pi retention in patients with
ESRD. The use of large doses of
calcium-containing Pi binders along with
calcitriol administration may contribute to over-suppression of
parathyroid hormone secretion and adynamic
bone disease as well as to a high incidence of
vascular calcifications. When used in patients with impaired renal function,
aluminium salts were found to accumulate in bone and other tissues, resulting in
osteomalacia and
encephalopathy.Sevelamer, an
aluminium- and
calcium-free Pi binder can reduce serum
phosphorus concentration and is associated with a significantly lower incidence of hypercalcaemia, while maintaining the ability to suppress
parathyroid hormone production. An additional benefit of
sevelamer is its ability to lower
low density lipoprotein-cholesterol and total
cholesterol levels.
Sevelamer attenuates the progression of
vascular calcifications in haemodialysis patients, which may lead to lower mortality. The use of
sevelamer in non-dialysed patients might aggravate
metabolic acidosis, common in these patients. Several other
calcium-free Pi binders are in development.
Lanthanum carbonate has shown significant promise in clinical trials in
ESRD patients.
Magnesium salts do not offer a significant advantage over currently available Pi binders. Their use is restricted to patients receiving dialysis since excess
magnesium must be removed by dialysis.
Iron-based compounds have shown variable efficacy in short-term clinical trials in small numbers of haemodialysis patients. Mixed
metal hydroxyl carbonate compounds have shown efficacy in animals but have not been studied in humans. Major safety issues include absorption of the
metal component with possible tissue accumulation and toxicity.