Fosrenol and Phosphorus Balance - Lanthanum Carbonate
Fosrenol and Phosphorus Balance - Lanthanum Carbonate
Positive phosphorus balance and hyperphosphatemia (increased serum phosphorus levels) are
 very common complications of people with advanced chronic kidney disease (i.e., stage 5 CKD),
 including chronic dialysis patients, and are associated with severe morbidity and increased
 mortality. Despite attempts to control serum phosphorus with dietary phosphorus restriction
 and the use of medicines that bind phosphorus in the gastrointestinal tract so that the
 phosphorus cannot be absorbed into the body( also called phosphate binders), chronic dialysis
 patients frequently remain hyperphosphatemic, particularly at the time when they commence
 each of their regular dialysis treatments.

 Fosrenol (lanthanum carbonate, manufactured by Shire Pharmaceuticals) is a gastrointestinal
 phosphate binder that appears to have the advantages of being safe, well tolerated and
 effective at binding phosphate. There are limited data on the magnitude of binding of
 phosphorus by Fosrenol in the human gastrointestinal tract of patients with chronic kidney
 disease.

 The specific aims for this proposal are as follows:

 1. To quantify, under precisely controlled metabolic balance conditions, the increase in
 fecal excretion of dietary phosphorus that occurs when patients undergoing chronic
 peritoneal dialysis (CPD) ingest Fosrenol (lanthanum carbonate).

 2. To examine a dose response relationship between Fosrenol treatment and fecal phosphorus
 excretion. The investigators will examine in CPD patients ingesting a constant
 phosphorus intake, how much additional phosphorus is excreted in the feces at three
 different dose levels of Fosrenol, 1.5, 3.0, and 4.5 g/day.

 3. To examine how increased fecal phosphorus losses and more negative phosphorus balance
 caused by Fosrenol intake affects serum phosphorus and such hormonal regulators of
 phosphorus metabolism as serum parathyroid hormone (PTH), fibroblast growth factor-23,
 25-hydroxycholecalciferol (25(OH)D3), 1,25-dihydroxycholecalciferol (1,25(OH)2D3) and
 fetuin-A.

 4. To assess whether there is any effect of Fosrenol and increased intestinal phosphate
 binding on protein-nitrogen balance.
Seven clinically stable patients who have been undergoing CPD for at least six months will be
 admitted to the General Clinical and Research Center (GCRC) at Harbor-UCLA Medical Center for
 46 days. During this time they will be fed, under strict metabolic balance study conditions,
 a constant energy and protein intake designed to meet their previously ascertained
 nutritional needs. Their dietary intakes of phosphorus, calcium and magnesium will be
 maintained constant throughout the 46 days of study at 1100 mg/day, 1000 mg/day and 200
 mg/day, respectively. Patients will be treated throughout the study with a constant
 peritoneal dialysis regimen that consists of either continuous ambulatory peritoneal dialysis
 with four dialysate exchanges daily or automated peritoneal dialysis in which they will each
 receive about four dialysate exchanges per night; and possibly day-time dialysate exchanges.
 The number and volume of dialysate exchanges and the dialysate glucose concentration may vary
 among patients according to their metabolic and clinical needs, but will be constant for each
 patient. Patients will adhere to standard metabolic balance protocols as the investigators
 have conducted during our many previous metabolic balance studies. These protocols will
 include participating in prescribed daily exercise regimens that are designed to maintain the
 patients' physical activity at their prestudy, outpatient levels.

 All patients will first undergo a 10 day Baseline period for metabolic equilibration during
 which time they will not receive any phosphate binder. They will then receive three periods
 of Fosrenol treatment with three different dose levels for 12 days each. During each of three
 periods, the patients will receive, in random order, one or two Fosrenol tablets that will
 provide 500, 1000, or 1500 mg with each of the three meals that they will be fed each day.
 Thus these CPD patients will receive in random order 1500, 3000 and 4500 mg/day of Fosrenol
 each prescribed for one 12 day period.

 Outcome Measurements. All urine, collected in 24 hour urine specimens, and all feces
 excreted, collected over four day periods, will be obtained continuously. Every 4 days a
 duplicate 24 hour diet will be prepared for chemical analyses. The above specimens will be
 analyzed for phosphorus, calcium and nitrogen by spectrographic, atomic absorption
 spectroscopic and Kjeldahl analyses, respectively. Serum phosphorus, calcium, parathyroid
 hormone (PTH), fibroblast growth factor-23, 25-hydroxycholecalciferol (25(OH)D3),
 1,25-dihydroxycholecalciferol (1,25(OH)2D3), fetuin-A, urea and creatinine will be measured
 in the fasting state at the beginning of the 40 day balance period and every 5 days.
 Anthropometry and other standard measurements that are routinely conducted during metabolic
 balance procedures will also be performed.
Inclusion Criteria:

 -  Chronic peritoneal dialysis treatment(CPD) for at least the previous six months,
 Clinically stable,

 -  Ages 30 to 65 years old,

 -  Both genders,

 -  Any racial or ethnic background,

 -  Evidence that the subject is capable of giving informed consent and of adhering to the
 study protocol.

 Exclusion Criteria:

 -  No inflammatory or catabolic illnesses.

 -  No hospitalizations within the previous three months except for vascular access
 revision,

 -  No severe heart, liver or lung failure,

 -  No cancer, other than basal cell carcinoma, systemic infections, vasculitis or other
 rheumatological diseases.