Philadelphia, Pa. (October 18, 2006) -- ¾ Newly published data from a large, two-year trial published in the November issue of Kidney International report on the effects of chronic kidney disease (CKD) on cognitive function in CKD Stage 5 patients with hyperphosphatemia (high serum phosphorus levels in the blood), who have been treated with phosphate binder therapy.
This study is particularly relevant, as there is evidence that individuals with reduced renal function experience a significantly greater decline in cognitive function compared to those with normal renal function. Such patients also suffer from hyperphosphatemia, a condition that if uncontrolled contributes to the development of secondary hyperparathyroidism, renal osteodystrophy and vascular calcification.
"While CKD Stage 5 patients experience deterioration in their cognitive function, our study documented that this decline is independent of the phosphate-binder therapy used to control their hyperphosphatemia," said lead investigator Paul Altmann, MD, FRCP, consultant nephrologist, Oxford Radcliffe Hospitals in England. "Specifically, the study found that the use of FOSRENOL as a phosphate binder does not negatively affect cognitive function as compared to standard phosphate binder therapy."
In the current analysis, five assessments of participants' attention and memory revealed that deterioration in cognitive function was similar in patients enrolled in a two-year, multicenter study comparing FOSRENOL and standard phosphate binder therapy. Cognitive function declined for most tests in both treatment groups during the study. Notably, the impairments in cognitive function generally related to the speed of task completion, not to the accuracy of test completion.
"Cognitive function is a critical issue for CKD Stage 5 patients, yet there is limited long-term data available in this specific area of study. Shire welcomes the publication of these data, which add further insights into the complex impact of CKD on overall health," said Dr. Raymond Pratt, Vice President, Scientific Leader, Renal Business Unit, Research and Development, Shire Pharmaceuticals.
Study Design Investigators conducted the cognitive function assessments at 41 U.S. sites in a subgroup of hemodialysis patients from a two-year, randomized, open-label comparator study of FOSRENOL versus standard therapy (sevelamer HCl, calcium and aluminum). After a one- to three-week washout period of previous phosphate binders, the patients entered a six-week dose titration period and then a long-term maintenance phase of up to two years' total study participation. Patients started FOSRENOL treatment at 750 milligrams per day (mg/day) or 1,500 mg/day, at the discretion of the investigator. The dose could be titrated up to 3,000 mg/day or down to 375 mg/day, as necessary.
Investigators assessed the participants' cognitive function using computer-controlled tasks from the Cognitive Drug Research (CDR) cognitive assessment system. The first three tasks of the CDR assessed the patient's attention span; the last two tasks were tests of the patient's memory. Researchers conducted the testing before dialysis at the second or third dialysis session of the week at the study start and during visits at 3.5 months (Visit 9), 6 months (Visit 12), 12 months (Visit 15), 18 months (Visit 18) and 24 months (Final Visit).
In total, 124 hemodialysis patients (47 on FOSRENOL; 77 on standard therapy) completed the full two years of treatment and all six cognitive function testing sessions. This study demonstrates that while cognitive function deteriorates in hemodialysis patients over a two-year period, use of FOSRENOL as a phosphate binder does not adversely affect cognitive function as compared with the use of standard therapy.
Managing Hyperphosphatemia Of the approximately 20 million Americans who have some form of kidney disease, more than 530,000 have developed CKD Stage 5. Even with dialysis and a low-phosphorus diet, most CKD Stage 5 patients in the United States will develop hyperphosphatemia (high phosphorus levels in the blood). Without effective treatment, hyperphosphatemia may lead to renal osteodystrophy, a collection of bone diseases characterized by bone pain, brittle bones, skeletal deformities and fractures. Evidence also shows that hyperphosphatemia may contribute to cardiovascular disease, which accounts for almost half of all deaths among dialysis patients. FOSRENOL is not indicated for the treatment of secondary hyperparathyroidism, vascular and nonvascular calcification, or cardiovascular or renal disease.
Phosphorus, an element found in nearly all foods, is absorbed from the gastrointestinal tract into the bloodstream. When the kidneys fail, they no longer effectively remove phosphorus. While the normal adult range for phosphorus is 2.5 to 4.5 mg/dL, the blood phosphorus levels of many patients on dialysis often exceed 6.5 mg/dL. Such levels have been linked to a significantly higher morbidity and mortality risk for patients who have undergone at least one year of dialysis. Research has shown that for each mg/dL increase in mean serum phosphorus, the relative risk of death increased by six percent. There are no controlled clinical trials with FOSRENOL demonstrating a reduction in morbidity or mortality.
Hyperphosphatemia is managed with a combination of dialysis, diet restriction and phosphorus-binding agents, since diet and dialysis alone generally cannot adequately control phosphorus levels. Such binders "soak up" phosphorus in the gastrointestinal tract, before it can be absorbed into the blood, and aid patients in maintaining acceptable levels of mean serum phosphorus.
Despite the availability of phosphorus-binding agents, it remains a challenge for some CKD Stage 5 patients to maintain target ranges. According to the Kidney Disease Outcomes Quality Initiative (K/DOQI) Clinical Practice Guidelines for Bone Metabolism and Disease, Guideline 3, Evaluation of Serum Phosphorus Levels, fewer than 30 percent of dialysis patients are able to maintain serum phosphorus levels in the target range.