Fosrenol and Phosphorus Balance - Lanthanum Carbonate
Condition: Chronic Kidney Failure; End-stage Renal Disease; Disorders Associated With Peritoneal Dialysis
MeSH terms: Kidney Diseases; Kidney Failure, Chronic; Renal Insufficiency
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): lanthanum carbonate
Intervention type(s): Drug
Intervention description(s): All patients will receive the following doses of lanthanum carbonate in random order for 10 -12 days each. O mg, 500 mg tid, 1000 mg tid, 1500 mg tid.
Other intervention name(s): Fosrenol
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Chronic renal failure; End-stage renal disease; Chronic peritoneal dialysis; Serum phosphorus; Hyperphosphatemia; Phosphate binders; Phosphate