"The U.S. Food and Drug Administration today approved Liposorber LA-15 System to treat pediatric patients with primary focal segmental glomerulosclerosis (FSGS) either before transplant, or after renal (kidney) transplantation in which there is re"...
Patients with chronic kidney disease (CKD) on dialysis retain phosphorus and can develop hyperphosphatemia. High serum phosphorus can precipitate serum calcium resulting in ectopic calcification. When the product of serum calcium and phosphorus concentrations (Ca x P) exceeds 55 mg2/dL2, there is an increased risk that ectopic calcification will occur. Hyperphosphatemia plays a role in the development of secondary hyperparathyroidism in renal insufficiency.
Treatment of hyperphosphatemia includes reduction in dietary intake of phosphate, inhibition of intestinal phosphate absorption with phosphate binders, and removal of phosphate with dialysis. Renagel taken with meals has been shown to decrease serum phosphorus concentrations in patients with CKD who are on dialysis.
Mechanism of Action
Renagel contains sevelamer hydrochloride, a non-absorbed binding crosslinked polymer. It contains multiple amines separated by one carbon from the polymer backbone. These amines exist in a protonated form in the intestine and interact with phosphate molecules through ionic and hydrogen bonding. By binding phosphate in the dietary tract and decreasing absorption, sevelamer hydrochloride lowers the phosphate concentration in the serum.
In addition to effects on serum phosphate levels, sevelamer hydrochloride has been shown to bind bile acids in vitro and in vivo in experimental animal models. Bile acid binding by ion exchange resins is a well-established method of lowering blood cholesterol. Because sevelamer binds bile acids, it may interfere with normal fat absorption and thus may reduce absorption of fat-soluble vitamins such as A, D and K. In clinical trials of sevelamer hydrochloride, both the mean total and LDL cholesterol declined by 15-31%. This effect is observed after 2 weeks. Triglycerides, HDL cholesterol and albumin did not change.
A mass balance study using 14C-sevelamer hydrochloride in 16 healthy male and female volunteers showed that sevelamer hydrochloride is not systemically absorbed. No absorption studies have been performed in patients with renal disease.
The ability of Renagel to lower serum phosphorus in CKD patients on dialysis was demonstrated in six clinical trials: one double-blind placebo controlled 2-week study (Renagel N=24); two open-label uncontrolled 8-week studies (Renagel N=220) and three active-controlled open-label studies with treatment durations of 8 to 52 weeks (Renagel N=256). Three of the active-controlled studies are described here. One is a crossover study with two 8-week periods comparing Renagel to an active-control. The second is a 52-week parallel study comparing Renagel with active-control. The third is a 12-week parallel study comparing Renagel and active-control in peritoneal dialysis patients.
Active-Control, Cross-Over Study in Hemodialysis Patients
Eighty-four CKD patients on hemodialysis who were hyperphosphatemic (serum phosphorus > 6.0 mg/dL) following a two-week phosphate binder washout period received Renagel and active-control for eight weeks each in random order. Treatment periods were separated by a two-week phosphate binder washout period. Patients started on treatment three times per day with meals. Over each eight-week treatment period, at three separate time points the dose of Renagel could be titrated up 1 capsule or tablet per meal (3 per day) to control serum phosphorus, the dose of active-control could also be altered to attain phosphate control. Both treatments significantly decreased mean serum phosphorus by about 2 mg/dL (Table 4).
Table 4: Mean Serum Phosphorus (mg/dL) at Baseline and Endpoint
|Baseline at End of Washout||8.4||8.0|
|Change from Baseline at Endpoint||-2.0*||-2.1*|
|(95% Confidence Interval)||(-2.5, -1.5)||(-2.6, -1.7)|
|*p < 0.0001, within treatment group comparison|
The distribution of responses is shown in Figure 2. The distributions are similar for sevelamer hydrochloride and active control. The median response is a reduction of about 2 mg/dL in both groups. About 50% of subjects have reductions between 1 and 3 mg/dL.
Figure 2: Percentage of patients (Y-axis) attaining a phosphorus
reduction from baseline (mg/dL) at least as great as the value of the X-axis.
Average daily Renagel dose at the end of treatment was 4.9 g (range of 0.0 to 12.6 g).
Active-Control, Parallel Study in Hemodialysis Patients
Two hundred CKD patients on hemodialysis who were hyperphosphatemic (serum phosphorus > 5.5 mg/dL) following a two-week phosphate binder washout period were randomized to receive Renagel 800 mg tablets (N=99) or an active-control (N=101). The two treatments produced similar decreases in serum phosphorus. At week 52, using last observation-carried-forward, Renagel and active-control both significantly decreased mean serum phosphorus (Table 5).
Table 5: Mean Serum Phosphorus (mg/dL) and Ion Product at
Baseline and Change from Baseline to End of Treatment
|Change from Baseline at Endpoint||-2.1||-1.8|
|Ca x Phosphorus Ion Product|
|Change from Baseline at Endpoint||-19.4||-14.2|
Sixty-one percent of Renagel patients and 73% of the control patients completed the full 52 weeks of treatment.
Figure 3, a plot of the phosphorus change from baseline for the completers, illustrates the durability of response for patients who are able to remain on treatment.
Figure 3: Mean Phosphorus Change from Baseline for Patients
who Completed 52 Weeks of Treatment
Average daily Renagel dose at the end of treatment was 6.5 g (range of 0.8 to 13 g).
Active-Control, Parallel Study in Peritoneal Dialysis Patients
One hundred and forty-three patients on peritoneal dialysis who were hyperphosphatemic (serum phosphorus > 5.5 mg/dL) following a two-week phosphate binder washout period were randomized to receive Renagel® (N=97) or active-control (N=46) open label for 12 weeks. Average daily Renagel dose at the end of treatment was 5.9 g (range 0.8 to 14.3 g). There were statistically significant changes in serum phosphorus (p < 0.001) for Renagel (-1.6 mg/dL from baseline of 7.5 mg/dL), similar to the active-control.
Last reviewed on RxList: 6/24/2011
This monograph has been modified to include the generic and brand name in many instances.
Additional Renagel Information
Renagel - User Reviews
Renagel User Reviews
Now you can gain knowledge and insight about a drug treatment with Patient Discussions.
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.