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significantly from 64.1+/-14.1 to 46.9+/-7.4 mg2/dL2 (p < 0.001) after six weeks of

sevelamer. A level of less than 50 mg2 /dL2
was reached by 68% of patients, and 95%
had less than 60 mg2 /dL2 . The mean dose
of sevelamer at the end of treatment was 3.1
+/- 0.6 g per day. As expected, calcium

declined from 9.2+/-0.5 to 8.7 mg/dL


(p<0.01) during the initial washout after

stopping calcium-based phosphate binders, but remained stable thereafter. Ionized

calcium did not change significantly
throughtout the washout and sevelamer
treatment. However, interruption of calcium
salts led to a 81% reduction of total calcium
intake. Conclusions. We confirmed in an
European sample of hemodialysis patients
that sevelamer can reduce phosphate levels
without inducing hypercalcemia. The drug
can also be successfully used to reduce
mean calcium-phosphate product levels
below 50 mg2 /dL2 , closer to normal
values. Although similar results can be
obtained with other phosphate binders, a
concomitant accumulation of aluminum,
calcium or magnesium could be detrimental
to patients.
Slatopolsky EA, Burke SK, Dillon MA, et al.
RenaGel(TM), a nonabsorbed

calcium- and aluminum-free


phosphate binder, lowers serum
phosphorus and parathyroid
hormone. Kidney International. Vol. 55(1) (pp 299-307), 1999.

This multicenter, open-label, dose-titration


study assessed the safety and efficacy of
RenaGelrho, a nonabsorbed calcium-and

aluminum-free phosphate binder, in lowering serum phosphorus. Secondary outcomes

were its effects on serum intact PTH and serum lipids. Methods. Phosphate binders were discontinued during a two-week

washout period. Patients whose serum


phosphorus was more than 6.0 mg/dl during
washout were eligible for treatment.
RenaGel(TM), at starting doses of two,
three, or four 440 mg capsules three times
per day with meals, was administered to 172
hemodialysis patients for eight weeks.
RenaGel(TM) could be increased by one
capsule per meal every two weeks as
necessary to achieve serum phosphorus
control. A second two-week washout period
followed. Results. Mean serum phosphorus
rose from 6.8 +/- 2.0 mg/dl at pre-washout to
9.1 +/- 2.4 mg/dl at the end of the washout period. It then declined to 6.6 +/- 1.9 mg/dl by the end of the eight- week RenaGel(TM) treatment period (P < 0.0001). Serum

phosphorus increased to 8.0+/- 2.2 mg/dl at the end of the second washout period. The mean dose at the end of RenaGel(TM)

treatment was 5.4 g per day. Eighty-four
percent of the patients previously used
calcium-based phosphate binders. As

expected, calcium declined during the initial washout period when calcium-based

phosphate binders were discontinued. Mean serum calcium declined from 9.6 +/- 1.0

mg/dl at pre-washout to 9.1 +/- 0.8 mg/dl


after washout. It then increased to 9.4 +/-

0.9 mg/dl by the end of RenaGel(TM)


treatment. Median serum iPTH increased
during the two-week washout from 208
pg/ml to 316 pg/ml and then declined to 224
pg/ml at the end of the eight-week treatment
period (P < 0.0001 vs. end of initial
washout). After eight weeks of treatment,
RenaGel(TM) reduced mean serum total
cholesterol from 171.0 +/- 43.1 mg/dl to
145.0 +/- 38.7 mg/dl (P < 0.0001) and mean
serum low-density lipoprotein cholesterol
from 102.0 +/- 34.9 mg/dl to 75.6 +/- 29.4
mg/dl (P < 0.0001). High-density lipoprotein
cholesterol, triglycerides, and serum albumin
did not change. Conclusions. RenaGel(TM),
a novel and calcium- plus aluminum-free
effective phosphate binder, can control
serum phosphorus and reduce the levels of
PTH and cholesterol without inducing
hypercalcemia or other side effects. Thus,
this new phosphate binder may be effective
in the treatment of renal osteodystrophy in
uremic patients.
Other studies - lanthanum

Hutchison AJ, Maes B, Vanwalleghem J, et


al.

Long-term efficacy and tolerability of lanthanum carbonate: Results from a 3-year study. Nephron Clinical

Practice. Vol. 102(2)(pp c61-c71),
2006.

Patients who participated in a 6-month,


randomized trial comparing lanthanum
carbonate with calcium carbonate were

eligible for a 24-week, open-label extension. Lanthanum carbonate-treated patients

continued taking their established






maintenance dose ('continued-lanthanum group') and calcium carbonate-treated

patients switched to lanthanum carbonate, 375-3,000 mg/day ('switch group'). Patients could also enter a further 2-year extension. Efficacy parameters, including serum

phosphate, were monitored. Results: Mean serum phosphate was ~1.80 mmol/l

throughout the trial. The percentage of
patients with controlled serum phosphate

(≤1.80 mmol/l) after the 6-month extension was 63.3 and 58.4% in the continued-

lanthanum and switch groups, respectively; after the 2-year extension, 54.4% of patients had controlled serum phosphate. After

discontinuation of calcium carbonate and initiation of lanthanum carbonate, the

hypercalcemia incidence was 2.7%,
compared with 20.2% during the double-
blind phase. calcium-phosphate product was maintained at an acceptable level.
Lanthanum carbonate was well tolerated; adverse events were mild/moderate and
mainly gastrointestinal. Conclusions:
Lanthanum carbonate maintains

effectiveness with continued tolerability for up to 3 years.


Use in Children

Civilibal M, Caliskan S, Adaletli I, et al.


Coronary artery calcifications in

children with end-stage renal


disease. Pediatric Nephrology. Vol.
21(10) (pp 1426-1433), 2006.
Coronary artery calcification (CAC) is

common in adults with ESRD, but little is


known about the prevalence and the extent

of it in children. We used multidetector spiral computed tomography (MDCT),

echocardiography, and carotid and brachial high-resolution ultrasonography to screen for the presence and predisposing factors of CAC in 53 children with ESRD [15

hemodialysis (HD) patients, 24 peritoneal dialysis (PD) patients, and 14 renal

transplant (rTx) recipients]. CAC was
present in 15% of patients (three HD

patients, three PD patients, and two rTx).


The mean age of the patients with CAC was

16.4 years (range: 11.0-21.2 years), and


their median CAC score was 101.3, ranging
from 8.5 to 4,322 according to the Agatston
method. The patients with CAC had longer
duration of total dialysis (P=0.005), had
higher time-integrated serum phosphorus
(P<0.001), calcium-phosphorus product

(P=0.012), intact PTH (P=0.010), vitamin B12 levels (P=0.010), the amount of cumulative calcium-containing oral phosphate binders (OBPs) (P<0.001), and calcitriol intake

(P<0.001), and had lower serum hemoglobin level (P=0.014). Interventricular septum

systolic thickness (P=0.033) was


significantly higher, relative wall thickness
(P=0.062) tended to be higher, and flow-
mediated endothelium-dependent dilatations
(P=0.071) were lower without reaching
statistically significant levels in those with
CAC. A stepwise logistic regression analysis
revealed that serum phosphorus (P=0.018)
and the cumulative exposure to calcium-
containing OPBs (P=0.016) were the most
significant independent predictors in the
development of CAC. These results indicate
that even adolescents and children with
ESRD may have coronary calcifications. We
concluded that impaired divalent ion
metabolism is the main factor in the
formation of CAC in this age group.

McElhiney LF.

Sevelamer suspension in children with end-stage renal disease.

International Journal of

Pharmaceutical Compound. Vol. 11(1) (pp 20-24), 2007.

Control of hyperphosphatemia is a major clinical challenge in children with ESRD. The best treatment option is a calcium-based phosphate binder, but there is evidence that this treatment protocol causes long-term complications, including vascular

calcifications. Sevelamer hydrochloride has been shown to be effective in reducing

serum phosphorus levels and the calcium-


phosphate product in children on

maintenance dialysis and may be key in preventing soft-tissue and vascular

calcifications in such patients. Until the U.S.
Food and Drug Administration approves the
use of sevelamer hydrochloride in children
undergoing dialysis, and a liquid dosage

form becomes available, compounding pharmacists will need to prepare this unique compound for these patients.


Pieper A-K, Haffner D, Hoppe B, et al.
A randomized crossover trial

comparing sevelamer with calcium acetate in children with CKD.








American Journal of Kidney


Diseases. Vol. 47(4)(pp 625-635),
2006.

A multicenter, randomized, open-label,


crossover study was performed to compare
the efficacy and safety of sevelamer, a
calcium-free phosphate binder, with calcium
acetate in pediatric patients with CKD.
Methods: Children (age, 0.9 to 18 years)
with CKD undergoing hemodialysis or
peritoneal dialysis or with a glomerular
filtration rate of 20 or greater and less than

60 mL/min/1.73 m2 (<0.33 and <1.00


mL/s/1.73 m2 were randomly assigned to the
following treatment scheme: 2 weeks of
washout followed by 8 weeks of treatment
with either sevelamer or calcium acetate in a
crossover fashion. Phosphorus, calcium,
and intact PTH in serum were measured
every 2 weeks, and phosphate binder
dosages were adjusted, if needed. Serum
lipid and vitamin concentrations were
measured at the beginning and end of each
treatment period. The primary end point was
the decrease in serum phosphorus levels
after 8 weeks of treatment. Results: Forty-
four patients were screened. Altogether,
data for 18 patients (5 girls) aged 12.4 +/-

4.1 years were used for the crossover


analysis. There was no significant difference
in serum phosphorus levels at 8 weeks after
the start of treatment in both groups. Total
cholesterol (-27%) and low-density
lipoprotein cholesterol (-34%) levels
decreased significantly with sevelamer
treatment (P < 0.02 and P < 0.005). An
increased incidence of hypercalcemia (P <

0.0005) was observed with calcium acetate


treatment, whereas metabolic acidosis was
more frequent with sevelamer treatment (P
< 0.005). Conclusion: Treatment of children
with CKD with sevelamer and calcium

acetate provides similar phosphorus level control. The marked decrease in lipid levels and lower rate of hypercalcemia may

augment the long-term benefit of sevelamer.
Williams R.

Sevelamer for treating

hyperphosphatemia in pediatric
CKD patients. Nature Clinical

Practice Nephrology. Vol. 2(6)(pp 296), 2006.

No Abstract available.
Salusky IB, Goodman WG, Sahney S, et al.
Sevelamer controls parathyroid

hormone-induced bone disease as efficiently as calcium carbonate

without increasing serum calcium
levels during therapy with active
vitamin D sterols. Journal of the
American Society of Nephrology.
Vol. 16(8)(pp 2501-2508), 2005.
The effects of calcium carbonate (CaCO3)

and sevelamer were compared in pediatric


peritoneal dialysis patients with bone biopsy-
proven 2degreesHPT. Twenty-nine patients
were randomly assigned to CaCO3 (n = 14)
or sevelamer (n = 15), concomitant with

either intermittent doses of oral calcitriol or doxercalciferol for 8 mo, when bone biopsies were repeated. Serum phosphorus, calcium, PTH, and alkaline phosphatase were

measured monthly. The skeletal lesions of 2degreesHPT improved with both binders, and bone formation rates reached the

normal range in approximately 75% of the


patients. Overall, serum phosphorus levels
were 5.5 +/- 0.1 and 5.6 +/- 0.3 mg/dl (NS)
with CaCO3 and sevelamer, respectively.
Serum calcium levels and the calcium-

phosphate product increased with CaCO3; in contrast, values remained unchanged with sevelamer (9.6 +/- 01 versus 8.9 +/- 0.2

mg/dl; P < 0.001, respectively).
Hypercalcemic episodes (>10.2 mg/dl)
occurred more frequently with CaCO3 (P <

0.01). Baseline PTH levels were 980 +/- 112


and 975 +/- 174 pg/ml (NS); these values
decreased to 369 +/- 92 (P < 0.01) and 562
+/- 164 pg/ml (P < 0.01) in the CaCO3 and
the sevelamer groups, respectively (NS

between groups). Serum alkaline


phosphatase levels also diminished in both
groups (P < 0.01). Thus, treatment with
either CaCO3 or sevelamer resulted in
equivalent control of the biochemical and
skeletal lesions of 2degreesHPT.
Sevelamer, however, maintained serum
calcium concentrations closer to the lower
end of the normal physiologic range, thereby
increasing the safety of treatment with active
vitamin D sterols.

Mahdavi H, Kuizon BD, Gales B, et al.


Sevelamer hydrochloride: An

effective phosphate binder in


dialyzed children. Pediatric

Nephrology. Vol. 18(12)(pp 1260-


1264), 2003.






This pilot study was designed to evaluate the efficacy and acceptability of sevelamer hydrochloride as a phosphate binder in

pediatric patients treated with dialysis. A 6-
month open-label trial of sevelamer

hydrochloride (Renagel) was initiated in 17 patients, aged 11.8+/-3.7 years, undergoing hemodialysis (n=3) or peritoneal dialysis

(n=14). Following a 2-week washout period of the phosphate binders, serum

phosphorus increased from 5.2+/-1.3 mg/dl to 7.5+/-2.2 mg/dl (P<0.0002). After initiation of therapy with sevelamer hydrochloride,

serum phosphorus levels decreased to

6.2+/-1.2 mg/dl (P<0.01) during the first 8


weeks and final values were 6.3+/-1.5 mg/dl.
Serum calcium concentration decreased
during the washout period from 9.4+/-0.9
mg/dl to 8.9+/-1.5 mg/dl (P<0.01); values
remained unchanged thereafter. The serum
calcium-phosphate product decreased
during the first 8 weeks and values did not
change subsequently. Serum bicarbonate,
PTH, total cholesterol, low-density
lipoprotein and high-density lipoprotein
cholesterol, and triglyceride levels did not
change. The initial prescribed dose of
sevelamer hydrochloride was 121+/-50
mg/kg (4.5+/-5 g/day) and the final
prescribed dose was 163+/-46 mg/kg (6.7+/-

2.4 g/day). Sevelamer hydrochloride was well tolerated and without adverse effects related to the drug.


Predictors of response
No papers found.
Safety

Altmann P, Barnett ME, Finn WF.


Cognitive function in Stage 5

chronic kidney disease patients on


hemodialysis: No adverse effects of
lanthanum carbonate compared with
standard phosphate-binder therapy.
Kidney International. Vol. 71(3)(pp
252-259), 2007.

Patients with Stage 5 CKD who have


hyperphosphatemia require treatment with
phosphate binders to lower serum
phosphorus levels. Existing binders are
effective but may be associated with
important safety disadvantages. Lanthanum
carbonate is a phosphate binder with demonstrated efficacy, safety, and

tolerability in clinical trials. Changes in


cognitive function were evaluated over time using the Cognitive Drug Research
computerized cognitive assessment system (Simple Reaction Time, Digit Vigilance Task, Choice Reaction Time, Numeric Working
Memory, and Delayed Picture Recognition) in 360 hemodialysis patients who were
enrolled in a 2-year, multicenter,

comparative study of lanthanum carbonate versus standard therapy. A decline in

cognitive function from baseline was
observed in both groups. The deterioration
in cognitive function was similar in both the
lanthanum carbonate and standard therapy
groups. One parameter - Numeric Working
Memory - showed a statistically significant
between-group difference in favor of
lanthanum carbonate (P=0.02). Given the
magnitude of the changes, however, and the
differences that were observed at baseline
between treatment groups, the clinical
significance of this difference is doubtful.
This study demonstrates that cognitive
function deteriorates in hemodialysis
patients over a 2-year time period. Use of
lanthanum carbonate as a phosphate binder
does not adversely affect cognitive function
compared with standard therapy.

De Santo NG, Frangiosa A, Anastasio P, et


al.

Sevelamer worsen metabolic


acidosis in hemodialysis patients.
Journal of Nephrology. Vol.
19(SUPPL. 9)(pp S108-S114),
2006.

Sevelamer hydrochloride, a major


phosphate binder for patients on

maintenance hemodialysis (MHD) is


associated with reduced serum bicarbonate concentration due to hydrochloric acid
release in the gut and to the binding of short chain fatty acids in the large intestine. Since metabolic acidosis can be deleterious, a
study was devised to compare the time
course of serum bicarbonate concentration during treatment with sevelamer

hydrochloride or calcium carbonate.


Methods: Sixteen well nourished patients on
NMD who were in excellent clinical
conditions and achieving target levels for
blood pressure (BP) and hemoglobin (Hb),
while on a protein intake of 1.1g/kg body






weight (bw), were enrolled in the study. After


a 2-week washout period, the patients were
divided into two groups, each consisting of
eight patients, and randomized either to 24
weeks of sevelamer followed by 24 weeks of
calcium carbonate (group A) or to 24 weeks
of calcium carbonate followed by 24 weeks
of sevelamer (group B). Protein intake, n-

protein catabolic rate (nPCR), serum


concentrations of calcium, phosphate,
calcium-phosphate product product,

bicarbonate, intact PTH and albumin were


monitored. Time course changes in serum
bicarbonate concentrations in relation to
short and long dialytic intervals (48 vs. 72
hr) were also investigated. Results: Both

sevelamer and calcium carbonate effectively controlled serum phosphate and the

calcium-phosphate product product. During calcium carbonate treatment plasma

phosphate concentrations were significantly below those of patients on sevelamer.

Plasma bicarbonate concentration fell within target DOQI values during calcium

carbonate administration both in group A and in group B, a goal which was not

achieved under sevelamer administration.
After a long dialytic interval in patients on

sevelamer, serum bicarbonate concentration averaged 17.3 +/- 1.1mEq/L, whereas it

averaged 21.1 +/- 0.7mEq/L in patients on
calcium carbonate (p<0.01). Finally, a 24-
week sevelamer administration caused a

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