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phosphate control over an 8-week period.
After a 2-week washout period, patients
crossed over to the alternate agent for 8
weeks. Eighty-four patients from eight
centers participated in the study. There was
a similar decrease in serum phosphate
values over the course of the study with both
sevelamer (-2.0 +/- 2.3 mg/dL) and calcium
acetate (- 2.1 +/- 1.9 mg/dL). Twenty-two
percent of patients developed a serum
calcium greater than 11.0 mg/dL while
receiving calcium acetate, versus 5% of
patients receiving sevelamer (P < 0.01). The
incidence of hypercalcemia for sevelamer
was not different from the incidence of
hypercalcemia during the washout period.
Patients treated with sevelamer also
sustained a 24% mean decrease in serum
low-density lipoprotein cholesterol levels.
Sevelamer was effective in controlling
hyperphosphatemia without resulting in an
increase in the Incidence of hypercalcemia
seen with calcium acetate. This agent
appears quite effective in the treatment of
hyperphosphatemia in hemodialysis
patients, and its usage may be

advantageous in the treatment of dialysis patients.

Chertow GM, Dillon M, Burke SK, et al.
A randomized trial of sevelamer

hydrochloride (RenaGel) with and without supplemental calcium.

Clinical Nephrology. Vol. 51(1)(pp 18-26), 1999.






We performed a randomized clinical trial to compare the efficacy of RenaGel alone and RenaGel with calcium, using the serum

phosphorus concentration and intact PTH as the principal outcomes of interest. Calcium (900 mg elemental) was provided as a once nightly dose on an empty stomach. 71

patients were randomized and included in


the intent-to-treat population; 55 completed
the 16-week study period (2 weeks washout,

12 weeks treatment, 2 weeks washout).


49% of subjects were taking vitamin D
metabolites. Results: Serum phosphorus
and PTH rose significantly when patients

stopped their phosphate binders during both washout periods. RenaGel and RenaGel

with calcium were equally effective at
reducing serum phosphorus (mean change -

2.4 mg/dL vs. -2.3 mg/dL). RenaGel with calcium was associated with a small

increase in serum calcium (mean change

0.3 mg/dL vs. 0.0 mg/dL in RenaGel group, P = 0.09) that was not statistically

significant. During the treatment phase, the reduction in PTH tended to be greater in the RenaGel with calcium group (median

change -67.0 vs. -22.5 pg/mL in RenaGel


group, P = 0.07). Non-users of vitamin D
metabolites treated with RenaGel with

calcium experienced a significant decrease in PTH (median change -114.5 vs. -22

pg/mL in RenaGel group, P = 0.006).
Adverse events were seen with equal

frequency in both groups, being generally


mild in intensity, and rarely attributable to
the drugs. Conclusion: We conclude that
RenaGel and RenaGel with calcium are

similarly effective in the treatment of ESRD-


related hyperphosphatemia. Provision of

supplemental calcium or metabolites of vitamin D with RenaGel may enhance control of hyperparathyroidism.


RCTs - lanthanum

Chiang S-S, Chen J-B, Yang W-C.


Lanthanum carbonate (Fosrenol)

efficacy and tolerability in the


treatment of hyperphosphatemic patients with end-stage renal
disease. Clinical Nephrology. Vol. 63(6) (pp 461-470), 2005.

Following a one- to three-week washout phase and a four-week, open-label

lanthanum carbonate dose-titration phase,
male and female hemodialysis patients were randomized (1:1) to receive either

lanthanum carbonate or placebo for four weeks. The primary efficacy parameter of the study was the control of serum

phosphorus levels (≤ 1.8 mmol/l [≤ 5.6
mg/dl]). Secondary endpoints included the
profile of serum phosphorus during titration
and PTH, calcium, and calcium-phosphate
product levels. The safety and tolerability of
lanthanum carbonate were assessed by
monitoring adverse events throughout the
study. Results: Mean serum phosphorus
level at the end of washout was 2.5 +/- 0.5
mmol/l (7.7 +/- 1.5 mg/dl; n = 73), and there
was no evidence of a difference in levels
between the treatment groups pre-
randomization. At the end of the study,
lanthanum carbonate-treated patients had
significantly lower phosphorus levels (1.6 +/-

0.5 mmol/l [5.1 +/- 1.5 mg/dl]; n = 30) than


those receiving placebo (2.3 +/- 6.4 mmol/l
[7.2 +/- 1.3 mg/dl]; n = 31; p < 0.001). In
addition, a significantly higher proportion of

patients receiving lanthanum carbonate had


controlled serum phosphorus levels (60%)
compared with the placebo group (10%; p <

0.001). calcium-phosphate product levels were also significantly lower in the

lanthanum carbonate group at the end of randomized treatment (p < 0.001).

Lanthanum carbonate was well tolerated; only one serious adverse event was

reported, which was unrelated to treatment. Conclusions: Lanthanum carbonate was

shown to be an effective and well-tolerated phosphate binder for the treatment of

hyperphosphatemia in Chinese patients with ESRD. This finding supports the results of previous US and European studies, which have also shown that lanthanum carbonate treatment effectively controls serum

phosphorus levels.

Hutchison AJ, Maes B, Vanwalleghem J, et
al.

Efficacy, tolerability, and safety of lanthanum carbonate in

hyperphosphatemia: A 6-month, randomized, comparative trial

versus calcium carbonate. Nephron Clinical Practice. Vol. 100(1)(pp c8-


c19), 2005.

This study compares lanthanum carbonate with calcium carbonate for control of serum phosphate in hemodialysis patients.




39


Methods: In this European multicentre study, 800 patients were randomised to receive

either lanthanum or calcium carbonate and the dose titrated over 5 weeks to achieve control of serum phosphate. Serum levels of phosphate, calcium and PTH were followed over the following 20 weeks. Results:

Around 65% of patients in each group


achieved phosphate control, but in the
calcium carbonate group this was at the

expense of significant hypercalcemia (20.2% of patients vs. 0.4%). Consequently,

calcium-phosphate product tended to be better controlled in the lanthanum group. Conclusion: This 6-month study

demonstrates that serum phosphate control with lanthanum carbonate (750-3,000

mg/day) is similar to that seen with calcium carbonate (1,500-9,000 mg/day), but with a significantly reduced incidence of

hypercalcemia. Lanthanum carbonate is well tolerated and may be more effective in

reducing calcium-phosphate product than calcium carbonate.
Al-Baaj F, Speake M, Hutchison AJ.
Control of serum phosphate by oral

lanthanum carbonate in patients


undergoing haemodialysis and
continuous ambulatory peritoneal
dialysis in a short-term, placebo-
controlled study. Nephrology

Dialysis Transplantation. Vol. 20(4) (pp 775-782), 2005.

This was a double-blind, placebo-controlled, parallel-group study consisting of three

phases: a 2 week washout period; a 4 week, open-label, dose-titration phase; and a 4

week, double-blind, placebo-controlled
phase. After washout, patients (n = 59)

received lanthanum (375 mg/day), titrated up to a maintenance dose (maximum: 2250 mg) that achieved control of serum

phosphate levels between 1.3 and 1.8
mmol/l (4.03-5.58 mg/dl). After titration,

patients were randomized to receive their maintenance dose of lanthanum (n = 17) or placebo (n = 19) for 4 weeks. Control of

serum phosphate was the primary efficacy assessment. Levels of calcium, PTH,

calcium-phosphate product and lanthanum as well as adverse events were evaluated. Results. By the end of titration, 70% of

patients had serum phosphate levels ≤1.8 mmol/l. Lanthanum carbonate continued to control serum phosphate levels in the
double-blind phase. At the end of the study,

64.7% of lanthanum carbonate-treated


patients were controlled compared with

21.4% in the placebo group. Results in


patients receiving continuous ambulatory
peritoneal dialysis (CAPD) were similar to

those seen in the group as a whole. Mean PTH levels (P = 0.41) and calcium-

phosphate product (P < 0.001) were both higher in the placebo than the lanthanum carbonate group. Conclusions. Lanthanum carbonate is an effective phosphate binder able to control serum phosphate and

calcium-phosphate product.

Finn WF, Joy MS, Hladik G, et al.
Efficacy and safety of lanthanum

carbonate for reduction of serum


phosphorus in patients with chronic renal failure receiving hemodialysis. Clinical Nephrology. Vol. 62(3)(pp 193-201), 2004.

196 patients (≥ 18 years) receiving


hemodialysis for at least 6 months entered a
1- to 3-week, single-blind, placebo run-in
phase. Of these, 145 patients were
randomized to a double-blind phase in which
they received placebo or lanthanum
carbonate in daily lanthanum doses of 225,
675, 1,350 or 2,250 mg for 6 weeks. Serum
levels of phosphorus, calcium and PTH, and
adverse events were monitored throughout
the study. Results: The intent-to-treat
analysis (n = 144) showed significant dose-
related reductions in serum phosphorus at
lanthanum doses of 675, 1,350 and 2,250
mg. After 6 weeks of treatment, phosphorus
levels were significantly lower in the
lanthanum groups receiving 1,350 mg/day
and 2,250 mg/day, compared with the
placebo group (respective changes from
randomization: -0.95 +/- 1.39 mg/dl (-0.31
+/- 0.45 mmol/l), -1.13 +/- 2.01 mg/dl (-0.36
+/- 0.65 mmol/l), 0.75 +/- 1.47 mg/dl (0.24
+/- 0.47 mmol/l), p < 0.001). Significant
reductions in serum phosphorus, compared
with placebo, occurred in the lanthanum
1,350 mg/day group from the second week
of treatment and in the 2,250 mg/day group
from the first week of treatment. Adverse
events were mainly gastrointestinal (e.g.
nausea and vomiting). Treatment-related
adverse events occurred in 39% of patients
treated with lanthanum carbonate and 44%
of the placebo group. Conclusion:
Lanthanum carbonate is an effective and






well-tolerated agent for the short-term


treatment of hyperphosphatemia in patients with ESRD.

Joy MS, Finn WF.

Randomized, double-blind, placebo-
controlled, dose-titration, phase III study assessing the efficacy and

tolerability of lanthanum carbonate: A new phosphate binder for the

treatment of hyperphosphatemia. American Journal of Kidney

Diseases. Vol. 42(1 SUPPL. 2)(pp 96-107), 2003.

This 16-week study assessed the control of serum phosphorus with lanthanum

carbonate, and its effects on serum calcium, calcium-phosphate product, and PTH.

Hemodialysis patients ≥18 years old entered
into a 1- to 3-week washout period during
which serum phosphorus levels rose to >5.9
mg/dL (1.90 mmol/L). In total, 126 patients
were titrated with lanthanum carbonate at
doses containing 375, 750, 1,500, 2,250, or
3,000 mg/d elemental lanthanum, given in
divided doses with meals over a 6-week

period, to achieve serum levels ≤5.9 mg/dL. By the end of dose titration, 11/126 (9%)

patients received ≤750 mg/d of lanthanum,

25 (20%) received 1,500 mg/d, 37 (29%)


received 2,250 mg/d, and 53 (42%) received
3,000 mg/d. Following titration, patients
were randomized to receive either
lanthanum carbonate or placebo during a 4-
week, double-blind maintenance phase.
Results: At the study endpoint, the mean
difference in serum phosphorus between the
lanthanum carbonate and placebo treatment
arms was 1.91 mg/dL (0.62 mmol/L) (P <

0.0001). calcium-phosphate product (P <

0.0001) and serum PTH levels (P < 0.01)
were also significantly lower with lanthanum
carbonate versus placebo. The incidence of
drug-related adverse events was similar

between placebo- and lanthanum


carbonate-treated patients. Conclusion:
Lanthanum carbonate is an effective and
well-tolerated agent for the treatment of
hyperphosphatemia in patients with ESRD.

D'Haese PC, Spasovski GB, et al. A


multicenter study on the effects of

lanthanum carbonate (Fosrenol) and calcium carbonate on renal bone

disease in dialysis patients. Kidney Int Suppl(85): S73-8, 2003.
In this phase III, open-label study, we
compared the effects of LC and calcium

carbonate (CaCO3) on the evolution of renal osteodystrophy (ROD) in dialysis patients. METHODS: Ninety-eight patients were

randomized to LC (N = 49) or CaCO3 (N =
49). Bone biopsies were taken at baseline
and after one year of treatment. Acceptable
paired biopsies were available for static and
dynamic histomorphometry studies in 33 LC
and 30 CaCO3 patients. Blood samples

were taken at regular intervals for


biochemical analysis and adverse events
were monitored. RESULTS: LC was well
tolerated and serum phosphate levels were
well controlled in both treatment groups. The
incidence of hypercalcemia was lower in the
LC group (6% vs. 49% for CaCO3). At
baseline, subtypes of ROD were similarly
distributed in both groups, with mixed ROD
being most common. At one-year follow-up
in the LC group, 5 of 7 patients with baseline
low bone turnover (either adynamic bone or
osteomalacia), and 4 of 5 patients with
baseline hyperparathyroidism, had evolved
toward a normalization of their bone
turnover. Only one lanthanum-treated
patient evolved toward adynamic bone
compared with 6 patients in the CaCO3
group. In the LC group, the number of
patients having either adynamic bone,
osteomalacia, or hyperpara decreased
overall from 12 (36%) at baseline to 6
(18%), while in the calcium group, the
number of patients with these types of ROD
increased from 13 (43%) to 16 (53%).
CONCLUSION: LC is a poorly absorbed,
well-tolerated, and efficient phosphate
binder. LC-treated dialysis patients show
almost no evolution toward low bone
turnover over one year (unlike CaCO3-
treated patients), nor do they experience
any aluminum-like effects on bone.
Other studies - sevelamer
Brewster UC, Ciampi MA, Abu-Alfa AK, et
al.

Long-term comparison of sevelamer hydrochloride to calcium-containing phosphate binders. Nephrology. Vol. 11(2) (pp 142-146), 2006.

This study compares the long-term efficacy of sevelamer hydrochloride to calcium-






containing binders (CCB). Methods: A


retrospective chart review was conducted in

30 patients receiving sevelamer

hydrochloride for >1 years and 25 patients receiving CCB. Results: Patients on

sevelamer hydrochloride had lower serum bicarbonate concentration than those on CCB, 18.6 +/- 2.7 versus 20.3 +/- 1.8

mmol/L (P = 0.0017). Serum phosphorus
concentration was higher in patients on

sevelamer hydrochloride compared to CCB

2.10 +/- 0.87 versus 1.74 +/- 0.28 mmol/L (P
= 0.0013), as was the Ca-P product 4.97 +/-

0.94 mmol2/L2 (62.1 +/- 11.8 mg2/dL2)


versus 3.97 +/- 1.18 mmol2/L2 (49.7 +/- 14.7
mg2/dL2, P = 0.0009). Only 36% of patients
on sevelamer hydrochloride compared with
68% on CCB (P = 0.015) met the serum
phosphorus goal of ≤1.78 mmol/L.
Conclusion: Patients on sevelamer
hydrochloride for >1 years compared to
those on CCB had a lower serum
bicarbonate concentration, a higher serum
phosphorus concentration and a higher Ca-
P product. Clinicians should balance the
increase in calcium load with CCB versus
the cost and effectiveness of sevelamer
hydrochloride in choosing a phosphate
binder for ESRD patients.
Yonova D, Georgiev M, Papazov V, et al.
RenaGel: Treatment of

hyperphosphatemia in dialysis


patients. Nephrology, Dialysis &

Transplantation. Vol. 11(1)(pp 42-


44), 2005.

To determine the effectiveness of RenaGel,


we performed a 6-month clinical trial in 14
adult patients with ESRD on hemodialysis.
Drug-related changes in the concentrations
of serum phosphorus, calcium, PTH, some
parameters of the coagulation and low- and
high-density lipoproteins were the major

outcomes of interest. Treatment with


RenaGel was associated with a significant
change in serum phosphorus and LDL-C.
There was no significant overall treatment-
related changes in PTH. Coagulation status
was not sizably disturbed and no elevation
of bleeding episodes was registered. The
study proved the effectiveness of sevelamer
against hyperphosphatemia - the 'silent
killer' of dialysis patients - and a quite
positive 'side' effect on lipid profile, and an
adequate tolerance of the drug without
serious complications.
Izumi M, Shirai K, Ito K, et al.
Is 2.5 mEq/L the optimal calcium

concentration of dialysate in the use of sevelamer hydrochloride? A study of the dialysate calcium

concentration recommended by K/DOQI guidelines. Therapeutic Apheresis & Dialysis. Vol. 9(1)(pp 24-31), 2005.

We tested the effect of three different


dialysate calcium concentrations on calcium-
phosphorus metabolism during the use of sevelamer hydrochloride. After a calcium-
containing phosphate binder was switched to sevelamer, the serum calcium,

phosphorus, and intact PTH levels and the markers of bone turnover were measured in the patients whose dialysate calcium

concentrations were 2.5, 2.75, and 3.0
mEq/L. As a result, in the 2.75-mEq/L group,
the serum calcium concentrations
decreased and the intact PTH level
increased significantly. In the 2.5-mEq/L
group, transient hypocalcemia occurred and
the levels of both bone-alkaline phosphatase
and osteocalcin increased. In the 3.0-mEq/L
group, the serum calcium concentrations did
not change significantly and only bone-
alkaline phosphatase increased. If a
calcium-containing phosphate binder is
completely switched to sevelamer, dialysis
using a dialysate calcium concentration
below 3.0 mEq/L may result in hypocalcemia
and acceleration of bone turnover.
Ando R, Naito S, Inagaki Y, et al.
The influence of dialysate calcium

on the therapeutic effects of


sevelamer hydrochloride in
hemodialysis patients with

secondary hyperparathyroidism


under treatment of intravenous

vitamin D metabolites. Therapeutic Apheresis & Dialysis. Vol. 9(1)(pp 16-23), 2005.

We investigated the influence of dialysate calcium on the therapeutic effect of

sevelamer in 40 hemodialysis patients who


are under treatment of intravenous vitamin D
metabolites for SHPT (VD(+)) and compared
the results with those of 41 patients who had
not received vitamin D metabolites (VD(-)).
Serum phosphorus and calcium-phosphate
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