Calcium salts of ketoacids as a new treatment strategy for uremic hyperphosphatemia

Hyperphosphatemia and secondary hyperparathyroidism are regular complications in patients suffering from end-stage renal failure. Aluminum-containing drugs are widely used to control serum phosphate, but this therapy carries the well-known risk of aluminum toxicity. Previously we demonstrated that a mixture of ketoacids is very effective in lowering increased serum phosphate and serum PTH levels. Recent studies to clarify the underlying mechanisms whereby these compounds lower serum phosphate revealed that ketoacids act as intestinal phosphate binders. In balance studies we demonstrated that intestinal phosphorus uptake decreased in normal subjects (decrease of absorption during ingestion: 0.7-3.14 mmol/day). Additional in vitro studies not only confirmed the in vivo results but also showed that ketoacids are as efficient as calcium carbonate although they provide less calcium. It is of further interest that ketoacids reached their greatest binding efficiency when the pH is 7.0, whereas calcium carbonate binds phosphate predominantly when the pH is 2.0 or 5.0. Ketoacids represent a further therapy to lower serum phosphate in uremia. As they provide less calcium than calcium carbonate, they could be considered as an advantageous, less dangerous alternative.