* PHOSPHATE CONC. IN BODY REGULATED BY : DIET, HORMONES & BLOOD PH
* ABSORPTION IS INCREASED BY : VIT D INTAKE & VERY LOW PHOSPHATE DIET
* ABSORPTION IS BLOCKED BY : ALUMINIUM-CALCIUM & MAGNESIUM CONTAINING ANTACIDS.
* BONE LOSSES ARE INFLUENCED BY : PTH , VIT D , SEX HORMONES, ACID BASE BALANCE & GENERALISED INFLAMMATION.
* EXCESS INGESTED PHOSPHATE IS EXCRETED BY KIDNEYS BY PROXIMAL RENAL TUBULES & DISTAL CONVOLUTED TUBULES.
Medical Care: The major strategies in treating hyperphosphatemia are (1) to diagnose the cause in order to initiate specific therapy, (2) to limit intake, and (3) to enhance renal excretion.
" If the cause of hyperphosphatemia can be determined, then specific treatment can be provided in some cases. For example, excessive ingestion of phosphate-containing purgatives or the administration of excessive quantities of parenteral phosphate is easily treatable by decreasing or discontinuing the supplements. Hyperphosphatemia due to renal failure is predominantly treated by limiting ingested quantities and by dialysis. Hyperphosphatemia due to tumor lysis responds to forced saline diuresis to enhance urinary losses.
" The clinical condition most often requiring curtailment of ingestion is renal failure. Because intestinal absorption of phosphate is unregulated and phosphate content in a typical diet is high, maintenance of phosphate homeostasis is dependent on renal excretion of the ingested excess. Therefore, when renal failure develops and hyperphosphatemia ensues, the sole means of controlling it is limitation of intake.
o Instruct patients with renal insufficiency and renal failure to avoid foods especially high in phosphate, such as dairy products.
o Dietary restriction alone may suffice for control of hyperphosphatemia in persons with mild renal insufficiency but is inadequate for control in those with advanced renal insufficiency or complete renal failure. These latter patients require the addition of phosphate binders to inhibit gastrointestinal absorption of phosphate. Phosphate binders are taken concomitantly with meals and work by directly interacting with the phosphate in the food, preventing intestinal absorption. Three classes of phosphate binders are widely used.
" The aluminum-containing binders were the first, but they have largely been abandoned because of the toxic effects of absorbed aluminum. Initially, the amount of aluminum absorbed was thought to be trivial; however, with long-term use, many patients developed a constellation of clinical symptoms attributable to aluminum. These included dementia, severe osteomalacia, and anemia. Bone biopsies performed on patients with aluminum intoxication revealed deposition of aluminum along the mineralizing front of bone, preventing normal mineralization. Aluminum levels in the fasting state and after a challenge with desferrioxamine confirmed the increased total body aluminum load.
" The next class of phosphate binders introduced and still used extensively today are the calcium-containing binders such as calcium carbonate and calcium citrate. These drugs have the advantage of providing a needed mineral, calcium, along with inhibiting phosphate absorption. The disadvantage of these drugs is the relatively high incidence of hypercalcemia and the more recent concerns about the contribution of large exogenous calcium loads to the occurrence of soft tissue calcification in end-stage renal disease.
" These concerns have led to the development of another class of phosphate binders that contain no aluminum or calcium. At present, 2 drugs of this class are in clinical use: sevelamer (Renagel) and lanthanum carbonate (Fosrenal). For patients with demonstrable extraskeletal calcification or recurrent hypercalcemia with calcium-containing phosphate binders, sevelamer is an excellent alternative. Sevelamer and calcium-containing phosphate binders can be used in combination to minimize adverse effects; however, the major barrier to their use is patient noncompliance. The patient is required to ingest 3-6 large capsules with every meal, which is more than most human beings can comply with for extended periods.
o An alternative therapy for dialysis-dependent patients that is presently being investigated is daily nocturnal dialysis. Dialysis performed in this manner, as opposed to intermittent thrice-weekly dialysis, seems to markedly decrease or even abolish the necessity for phosphate binders.
o Just as better control of hyperphosphatemia in renal failure patients helps prevent the nearly universal development of secondary hyperparathyroidism, better control of hyperphosphatemia is also achieved through control of secondary hyperparathyroidism. The agents commonly used to control secondary hyperparathyroidism are vitamin D metabolites and, more recently, the calcium-sensing receptor agonists.
" The strategy for treatment of hyperphosphatemia for patients with normal renal function and hyperphosphatemia is to enhance renal excretion. This can be accomplished most effectively by a combination of volume repletion with saline coupled with forced diuresis with a loop diuretic such as furosemide or bumetanide.
o The marked increase in intravascular volume with saline globally inhibits proximal renal tubule absorption of solutes, in this specific case, phosphate, thus promoting phosphaturia.
o The increased distal tubule delivery of phosphate overwhelms the ability of that portion of the nephron to absorb phosphate, leading to a negative phosphate balance.
" For the rare cases of hypoparathyroidism, calcium and vitamin D are prescribed. PTH injections or infusions could be considered but are impractical and not used in clinical practice.
Surgical Care: Surgery may sometimes be required for removal of large calcium phosphate deposits occurring in patients with tumoral calcinosis or long-standing renal failure. Perform parathyroidectomy in patients with renal failure who have tertiary (autonomous) hyperparathyroidism complicated by hypercalcemia, hyperphosphatemia, and severe bone disease.
Diet: When dietary phosphate intake is a significant contributor to hyperphosphatemia, such as with renal failure, dietary phosphate restriction is appropriate. Foods high in phosphate include dairy products, meats, nuts, and other high-protein foods.
Activity: Hyperphosphatemia does not mandate any alteration in physical activity; however, deposition of calcium deposits in joints may limit certain activities.
DRUG TREATMENT : GOALS OF TREATMENT IS TO REDUCE PHOSPHATE LEVELS & PREVENT COMPLICATIONS.
1. DIURETICS :
- FRUSEMIDE
2. PHOSPHATE BINDERS :
- ALUMINIUM HYDROXIDE
- CALCIUM CARBONATE
- CALCIUM ACETATE
- CALCIUM CITRATE
- MAGNESIUM HYDROXIDE
- SEVELAMER HYDROCHLORIDE
- LANTHANUM CARBONATE